A comparison between ten advanced and soft computing models for groundwater qanat potential assessment in Iran using R and GIS

NASA Astrophysics Data System (ADS)

Naghibi, Seyed Amir; Pourghasemi, Hamid Reza; Abbaspour, Karim

2018-02-01

Considering the unstable condition of water resources in Iran and many other countries in arid and semi-arid regions, groundwater studies are very important. Therefore, the aim of this study is to model groundwater potential by qanat locations as indicators and ten advanced and soft computing models applied to the Beheshtabad Watershed, Iran. Qanat is a man-made underground construction which gathers groundwater from higher altitudes and transmits it to low land areas where it can be used for different purposes. For this purpose, at first, the location of the qanats was detected using extensive field surveys. These qanats were classified into two datasets including training (70%) and validation (30%). Then, 14 influence factors depicting the region's physical, morphological, lithological, and hydrological features were identified to model groundwater potential. Linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), flexible discriminant analysis (FDA), penalized discriminant analysis (PDA), boosted regression tree (BRT), random forest (RF), artificial neural network (ANN), K-nearest neighbor (KNN), multivariate adaptive regression splines (MARS), and support vector machine (SVM) models were applied in R scripts to produce groundwater potential maps. For evaluation of the performance accuracies of the developed models, ROC curve and kappa index were implemented. According to the results, RF had the best performance, followed by SVM and BRT models. Our results showed that qanat locations could be used as a good indicator for groundwater potential. Furthermore, altitude, slope, plan curvature, and profile curvature were found to be the most important influence factors. On the other hand, lithology, land use, and slope aspect were the least significant factors. The methodology in the current study could be used by land use and terrestrial planners and water resource managers to reduce the costs of groundwater resource discovery.

Functional Morphometric Analysis of the Furcula in Mesozoic Birds

PubMed Central

Close, Roger A.; Rayfield, Emily J.

2012-01-01

The furcula displays enormous morphological and structural diversity. Acting as an important origin for flight muscles involved in the downstroke, the form of this element has been shown to vary with flight mode. This study seeks to clarify the strength of this form-function relationship through the use of eigenshape morphometric analysis coupled with recently developed phylogenetic comparative methods (PCMs), including phylogenetic Flexible Discriminant Analysis (pFDA). Additionally, the morphospace derived from the furculae of extant birds is used to shed light on possible flight adaptations of Mesozoic fossil taxa. While broad conclusions of earlier work are supported (U-shaped furculae are associated with soaring, strong anteroposterior curvature with wing-propelled diving), correlations between form and function do not appear to be so clear-cut, likely due to the significantly larger dataset and wider spectrum of flight modes sampled here. Interclavicular angle is an even more powerful discriminator of flight mode than curvature, and is positively correlated with body size. With the exception of the close relatives of modern birds, the ornithuromorphs, Mesozoic taxa tend to occupy unique regions of morphospace, and thus may have either evolved unfamiliar flight styles or have arrived at similar styles through divergent musculoskeletal configurations. PMID:22666324

A Novel Hyperspectral Microscopic Imaging System for Evaluating Fresh Degree of Pork.

PubMed

Xu, Yi; Chen, Quansheng; Liu, Yan; Sun, Xin; Huang, Qiping; Ouyang, Qin; Zhao, Jiewen

2018-04-01

This study proposed a rapid microscopic examination method for pork freshness evaluation by using the self-assembled hyperspectral microscopic imaging (HMI) system with the help of feature extraction algorithm and pattern recognition methods. Pork samples were stored for different days ranging from 0 to 5 days and the freshness of samples was divided into three levels which were determined by total volatile basic nitrogen (TVB-N) content. Meanwhile, hyperspectral microscopic images of samples were acquired by HMI system and processed by the following steps for the further analysis. Firstly, characteristic hyperspectral microscopic images were extracted by using principal component analysis (PCA) and then texture features were selected based on the gray level co-occurrence matrix (GLCM). Next, features data were reduced dimensionality by fisher discriminant analysis (FDA) for further building classification model. Finally, compared with linear discriminant analysis (LDA) model and support vector machine (SVM) model, good back propagation artificial neural network (BP-ANN) model obtained the best freshness classification with a 100 % accuracy rating based on the extracted data. The results confirm that the fabricated HMI system combined with multivariate algorithms has ability to evaluate the fresh degree of pork accurately in the microscopic level, which plays an important role in animal food quality control.

A Novel Hyperspectral Microscopic Imaging System for Evaluating Fresh Degree of Pork

PubMed Central

Xu, Yi; Chen, Quansheng; Liu, Yan; Sun, Xin; Huang, Qiping; Ouyang, Qin; Zhao, Jiewen

2018-01-01

Abstract This study proposed a rapid microscopic examination method for pork freshness evaluation by using the self-assembled hyperspectral microscopic imaging (HMI) system with the help of feature extraction algorithm and pattern recognition methods. Pork samples were stored for different days ranging from 0 to 5 days and the freshness of samples was divided into three levels which were determined by total volatile basic nitrogen (TVB-N) content. Meanwhile, hyperspectral microscopic images of samples were acquired by HMI system and processed by the following steps for the further analysis. Firstly, characteristic hyperspectral microscopic images were extracted by using principal component analysis (PCA) and then texture features were selected based on the gray level co-occurrence matrix (GLCM). Next, features data were reduced dimensionality by fisher discriminant analysis (FDA) for further building classification model. Finally, compared with linear discriminant analysis (LDA) model and support vector machine (SVM) model, good back propagation artificial neural network (BP-ANN) model obtained the best freshness classification with a 100 % accuracy rating based on the extracted data. The results confirm that the fabricated HMI system combined with multivariate algorithms has ability to evaluate the fresh degree of pork accurately in the microscopic level, which plays an important role in animal food quality control. PMID:29805285

Assessing the activity of perianal Crohn's disease: comparison of clinical indices and computer-assisted anal ultrasound.

PubMed

Losco, Alessandra; Viganò, Chiara; Conte, Dario; Cesana, Bruno Mario; Basilisco, Guido

2009-05-01

Assessing perianal disease activity is important for the treatment and prognosis of Crohn's disease (CD) patients, but the diagnostic accuracy of the activity indices has not yet been established. The aim of this study was to determine the accuracy and agreement of the Fistula Drainage Assessment (FDA), Perianal Disease Activity Index (PDAI), and computer-assisted anal ultrasound imaging (AUS). Sixty-two consecutive patients with CD and perianal fistulae underwent clinical, FDA, PDAI, and AUS evaluation. Perianal disease was considered active in the presence of visible fistula drainage and/or signs of local inflammation (induration and pain at digital compression) upon clinical examination. The AUS images were analyzed by calculating the mean gray-scale tone of the lesion. The PDAI and gray-scale tone values discriminating active and inactive perianal disease were defined using receiver operating characteristics statistics. Perianal disease was active in 46 patients. The accuracy of the FDA was 87% (confidence interval [CI]: 76%-94%). A PDAI of >4 and a mean gray-scale tone value of 117 maximized sensitivity and specificity; their diagnostic accuracy was, respectively, 87% (CI: 76%-94%) and 81% (CI: 69%-90%). The agreement of the 3 evaluations was fair to moderate. The addition of AUS to the PDAI or FDA increased their diagnostic accuracy to respectively 95% and 98%. The diagnostic accuracy of the FDA, PDAI, and computer-assisted AUS imaging was good in assessing perianal disease activity in patients with CD. The agreement between the techniques was fair to moderate. Overall accuracy can be increased by combining the FDA or PDAI with AUS.

Environmental Impact Analysis Process. Environmental Assessment for Defense Satellite Communications System III With Integrated Apogee Boost System

DTIC Science & Technology

1995-07-01

spectabilis Royal fern C FDA n/o Remirea maritima Beach star E FDA, FNAI o Scaevola plumeria Scaevola T FDA o Tillandsia simulata Wildpine; air plant...unnamed) T FDA n/o Tillandsia utriculata Giant wildpine; giant air plant C FDA o 1 E = Endangered; T = Threatened; T(S/A) = Threatened due to

Classification of phytoplankton cells as live or dead using the vital stains fluorescein diacetate and 5-chloromethylfluorescein diacetate.

PubMed

MacIntyre, Hugh L; Cullen, John J

2016-08-01

Regulations for ballast water treatment specify limits on the concentrations of living cells in discharge water. The vital stains fluorescein diacetate (FDA) and 5-chloromethylfluorescein diacetate (CMFDA) in combination have been recommended for use in verification of ballast water treatment technology. We tested the effectiveness of FDA and CMFDA, singly and in combination, in discriminating between living and heat-killed populations of 24 species of phytoplankton from seven divisions, verifying with quantitative growth assays that uniformly live and dead populations were compared. The diagnostic signal, per-cell fluorescence intensity, was measured by flow cytometry and alternate discriminatory thresholds were defined statistically from the frequency distributions of the dead or living cells. Species were clustered by staining patterns: for four species, the staining of live versus dead cells was distinct, and live-dead classification was essentially error free. But overlap between the frequency distributions of living and heat-killed cells in the other taxa led to unavoidable errors, well in excess of 20% in many. In 4 very weakly staining taxa, the mean fluorescence intensity in the heat-killed cells was higher than that of the living cells, which is inconsistent with the assumptions of the method. Applying the criteria of ≤5% false negative plus ≤5% false positive errors, and no significant loss of cells due to staining, FDA and FDA+CMFDA gave acceptably accurate results for only 8-10 of 24 species (i.e., 33%-42%). CMFDA was the least effective stain and its addition to FDA did not improve the performance of FDA alone. © 2016 The Authors. Journal of Phycology published by Wiley Periodicals, Inc. on behalf of Phycological Society of America.

Machine Learning Principles Can Improve Hip Fracture Prediction.

PubMed

Kruse, Christian; Eiken, Pia; Vestergaard, Peter

2017-04-01

Apply machine learning principles to predict hip fractures and estimate predictor importance in Dual-energy X-ray absorptiometry (DXA)-scanned men and women. Dual-energy X-ray absorptiometry data from two Danish regions between 1996 and 2006 were combined with national Danish patient data to comprise 4722 women and 717 men with 5 years of follow-up time (original cohort n = 6606 men and women). Twenty-four statistical models were built on 75% of data points through k-5, 5-repeat cross-validation, and then validated on the remaining 25% of data points to calculate area under the curve (AUC) and calibrate probability estimates. The best models were retrained with restricted predictor subsets to estimate the best subsets. For women, bootstrap aggregated flexible discriminant analysis ("bagFDA") performed best with a test AUC of 0.92 [0.89; 0.94] and well-calibrated probabilities following Naïve Bayes adjustments. A "bagFDA" model limited to 11 predictors (among them bone mineral densities (BMD), biochemical glucose measurements, general practitioner and dentist use) achieved a test AUC of 0.91 [0.88; 0.93]. For men, eXtreme Gradient Boosting ("xgbTree") performed best with a test AUC of 0.89 [0.82; 0.95], but with poor calibration in higher probabilities. A ten predictor subset (BMD, biochemical cholesterol and liver function tests, penicillin use and osteoarthritis diagnoses) achieved a test AUC of 0.86 [0.78; 0.94] using an "xgbTree" model. Machine learning can improve hip fracture prediction beyond logistic regression using ensemble models. Compiling data from international cohorts of longer follow-up and performing similar machine learning procedures has the potential to further improve discrimination and calibration.

OpenVigil FDA - Inspection of U.S. American Adverse Drug Events Pharmacovigilance Data and Novel Clinical Applications.

PubMed

Böhm, Ruwen; von Hehn, Leocadie; Herdegen, Thomas; Klein, Hans-Joachim; Bruhn, Oliver; Petri, Holger; Höcker, Jan

2016-01-01

Pharmacovigilance contributes to health care. However, direct access to the underlying data for academic institutions and individual physicians or pharmacists is intricate, and easily employable analysis modes for everyday clinical situations are missing. This underlines the need for a tool to bring pharmacovigilance to the clinics. To address these issues, we have developed OpenVigil FDA, a novel web-based pharmacovigilance analysis tool which uses the openFDA online interface of the Food and Drug Administration (FDA) to access U.S. American and international pharmacovigilance data from the Adverse Event Reporting System (AERS). OpenVigil FDA provides disproportionality analyses to (i) identify the drug most likely evoking a new adverse event, (ii) compare two drugs concerning their safety profile, (iii) check arbitrary combinations of two drugs for unknown drug-drug interactions and (iv) enhance the relevance of results by identifying confounding factors and eliminating them using background correction. We present examples for these applications and discuss the promises and limits of pharmacovigilance, openFDA and OpenVigil FDA. OpenVigil FDA is the first public available tool to apply pharmacovigilance findings directly to real-life clinical problems. OpenVigil FDA does not require special licenses or statistical programs.

An evaluation of the FDA's analysis of the costs and benefits of the graphic warning label regulation.

PubMed

Chaloupka, Frank J; Warner, Kenneth E; Acemoğlu, Daron; Gruber, Jonathan; Laux, Fritz; Max, Wendy; Newhouse, Joseph; Schelling, Thomas; Sindelar, Jody

2015-03-01

The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration (FDA) regulatory authority over cigarettes and smokeless tobacco products and authorised it to assert jurisdiction over other tobacco products. As with other Federal agencies, FDA is required to assess the costs and benefits of its significant regulatory actions. To date, FDA has issued economic impact analyses of one proposed and one final rule requiring graphic warning labels (GWLs) on cigarette packaging and, most recently, of a proposed rule that would assert FDA's authority over tobacco products other than cigarettes and smokeless tobacco. Given the controversy over the FDA's approach to assessing net economic benefits in its proposed and final rules on GWLs and the importance of having economic impact analyses prepared in accordance with sound economic analysis, a group of prominent economists met in early 2014 to review that approach and, where indicated, to offer suggestions for an improved analysis. We concluded that the analysis of the impact of GWLs on smoking substantially underestimated the benefits and overestimated the costs, leading the FDA to substantially underestimate the net benefits of the GWLs. We hope that the FDA will find our evaluation useful in subsequent analyses, not only of GWLs but also of other regulations regarding tobacco products. Most of what we discuss applies to all instances of evaluating the costs and benefits of tobacco product regulation and, we believe, should be considered in FDA's future analyses of proposed rules. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

An evaluation of the FDA's analysis of the costs and benefits of the graphic warning label regulation

PubMed Central

Chaloupka, Frank J; Warner, Kenneth E; Acemoğlu, Daron; Gruber, Jonathan; Laux, Fritz; Max, Wendy; Newhouse, Joseph; Schelling, Thomas; Sindelar, Jody

2015-01-01

The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration (FDA) regulatory authority over cigarettes and smokeless tobacco products and authorised it to assert jurisdiction over other tobacco products. As with other Federal agencies, FDA is required to assess the costs and benefits of its significant regulatory actions. To date, FDA has issued economic impact analyses of one proposed and one final rule requiring graphic warning labels (GWLs) on cigarette packaging and, most recently, of a proposed rule that would assert FDA’s authority over tobacco products other than cigarettes and smokeless tobacco. Given the controversy over the FDA's approach to assessing net economic benefits in its proposed and final rules on GWLs and the importance of having economic impact analyses prepared in accordance with sound economic analysis, a group of prominent economists met in early 2014 to review that approach and, where indicated, to offer suggestions for an improved analysis. We concluded that the analysis of the impact of GWLs on smoking substantially underestimated the benefits and overestimated the costs, leading the FDA to substantially underestimate the net benefits of the GWLs. We hope that the FDA will find our evaluation useful in subsequent analyses, not only of GWLs but also of other regulations regarding tobacco products. Most of what we discuss applies to all instances of evaluating the costs and benefits of tobacco product regulation and, we believe, should be considered in FDA's future analyses of proposed rules. PMID:25550419

Amendment to examination and investigation sample requirements--FDA. Direct final rule.

PubMed

1998-09-25

The Food and Drug Administration (FDA) is amending its regulations regarding the collection of twice the quantity of food, drug, or cosmetic estimated to be sufficient for analysis. This action increases the dollar amount that FDA will consider to determine whether to routinely collect a reserve sample of a food, drug, or cosmetic product in addition to the quantity sufficient for analysis. Experience has demonstrated that the current dollar amount does not adequately cover the cost of most quantities sufficient for analysis plus reserve samples. This direct final rule is part of FDA's continuing effort to achieve the objectives of the President's "Reinventing Government" initiative, and is intended to reduce the burden of unnecessary regulations on food, drugs, and cosmetics without diminishing the protection of the public health. Elsewhere in this issue of the Federal Register, FDA is publishing a companion proposed rule under FDA's usual procedures for notice and comment to provide a procedural framework to finalize the rule in the event the agency receives any significant adverse comment and withdraws this direct final rule.

Applications of functional data analysis: A systematic review.

PubMed

Ullah, Shahid; Finch, Caroline F

2013-03-19

Functional data analysis (FDA) is increasingly being used to better analyze, model and predict time series data. Key aspects of FDA include the choice of smoothing technique, data reduction, adjustment for clustering, functional linear modeling and forecasting methods. A systematic review using 11 electronic databases was conducted to identify FDA application studies published in the peer-review literature during 1995-2010. Papers reporting methodological considerations only were excluded, as were non-English articles. In total, 84 FDA application articles were identified; 75.0% of the reviewed articles have been published since 2005. Application of FDA has appeared in a large number of publications across various fields of sciences; the majority is related to biomedicine applications (21.4%). Overall, 72 studies (85.7%) provided information about the type of smoothing techniques used, with B-spline smoothing (29.8%) being the most popular. Functional principal component analysis (FPCA) for extracting information from functional data was reported in 51 (60.7%) studies. One-quarter (25.0%) of the published studies used functional linear models to describe relationships between explanatory and outcome variables and only 8.3% used FDA for forecasting time series data. Despite its clear benefits for analyzing time series data, full appreciation of the key features and value of FDA have been limited to date, though the applications show its relevance to many public health and biomedical problems. Wider application of FDA to all studies involving correlated measurements should allow better modeling of, and predictions from, such data in the future especially as FDA makes no a priori age and time effects assumptions.

Applications of functional data analysis: A systematic review

PubMed Central

2013-01-01

Background Functional data analysis (FDA) is increasingly being used to better analyze, model and predict time series data. Key aspects of FDA include the choice of smoothing technique, data reduction, adjustment for clustering, functional linear modeling and forecasting methods. Methods A systematic review using 11 electronic databases was conducted to identify FDA application studies published in the peer-review literature during 1995–2010. Papers reporting methodological considerations only were excluded, as were non-English articles. Results In total, 84 FDA application articles were identified; 75.0% of the reviewed articles have been published since 2005. Application of FDA has appeared in a large number of publications across various fields of sciences; the majority is related to biomedicine applications (21.4%). Overall, 72 studies (85.7%) provided information about the type of smoothing techniques used, with B-spline smoothing (29.8%) being the most popular. Functional principal component analysis (FPCA) for extracting information from functional data was reported in 51 (60.7%) studies. One-quarter (25.0%) of the published studies used functional linear models to describe relationships between explanatory and outcome variables and only 8.3% used FDA for forecasting time series data. Conclusions Despite its clear benefits for analyzing time series data, full appreciation of the key features and value of FDA have been limited to date, though the applications show its relevance to many public health and biomedical problems. Wider application of FDA to all studies involving correlated measurements should allow better modeling of, and predictions from, such data in the future especially as FDA makes no a priori age and time effects assumptions. PMID:23510439

Body Shape and Life Style of the Extinct Balearic Dormouse Hypnomys (Rodentia, Gliridae): New Evidence from the Study of Associated Skeletons

PubMed Central

Bover, Pere; Alcover, Josep A.; Michaux, Jacques J.; Hautier, Lionel; Hutterer, Rainer

2010-01-01

Hypnomys is a genus of Gliridae (Rodentia) that occurred in the Balearic Islands until Late Holocene. Recent finding of a complete skeleton of the chronospecies H. morpheus (Late Pleistocene-Early Holocene) and two articulated skeletons of H. cf. onicensis (Late Pliocene) allowed the inference of body size and the calculation of several postcranial indexes. We also performed a Factorial Discriminant Analysis (FDA) in order to evaluate locomotory behaviour and body shape of the taxa. Using allometric models based on skull and tooth measurements, we calculated a body weight between 173 and 284 g for H. morpheus, and direct measurements of articulated skeletons yielded a Head and Body Length (HBL) of 179 mm and a Total Body Length of 295 mm for this species. In addition to the generally higher robustness of postcranial bones already recorded by previous authors, H. morpheus, similar to Canariomys tamarani, another extinct island species, displayed elongated zygopodium bones of the limbs and a wider distal humerus and femur than in an extant related taxon, Eliomys quercinus. Indexes indicated that Hypnomys was more terrestrial and had greater fossorial abilities than E. quercinus. This was also corroborated by a Discriminant Analysis, although no clear additional inference of locomotory abilities could be calculated. PMID:21209820

Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis.

PubMed

Wang, Bo; Franklin, Jessica M; Eddings, Wesley; Landon, Joan; Kesselheim, Aaron S

2016-01-01

Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved ("off-label") uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children. Retrospective, segmented time-series analysis using new prescription claims during 2003-2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone. During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79). The FDA's sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency's expert judgments to clinical practice.

Development of hybrid fog detection algorithm (FDA) using satellite and ground observation data for nighttime

NASA Astrophysics Data System (ADS)

Kim, So-Hyeong; Han, Ji-Hae; Suh, Myoung-Seok

2017-04-01

In this study, we developed a hybrid fog detection algorithm (FDA) using AHI/Himawari-8 satellite and ground observation data for nighttime. In order to detect fog at nighttime, Dual Channel Difference (DCD) method based on the emissivity difference between SWIR and IR1 is most widely used. DCD is good at discriminating fog from other things (middle/high clouds, clear sea and land). However, it is difficult to distinguish fog from low clouds. In order to separate the low clouds from the pixels that satisfy the thresholds of fog in the DCD test, we conducted supplementary tests such as normalized local standard derivation (NLSD) of BT11 and the difference of fog top temperature (BT11) and air temperature (Ta) from NWP data (SST from OSTIA data). These tests are based on the larger homogeneity of fog top than low cloud tops and the similarity of fog top temperature and Ta (SST). Threshold values for the three tests were optimized through ROC analysis for the selected fog cases. In addition, considering the spatial continuity of fog, post-processing was performed to detect the missed pixels, in particular, at edge of fog or sub-pixel size fog. The final fog detection results are presented by fog probability (0 100 %). Validation was conducted by comparing fog detection probability with the ground observed visibility data from KMA. The validation results showed that POD and FAR are ranged from 0.70 0.94 and 0.45 0.72, respectively. The quantitative validation and visual inspection indicate that current FDA has a tendency to over-detect the fog. So, more works which reducing the FAR is needed. In the future, we will also validate sea fog using CALIPSO data.

Food and Drug Administration criteria for the diagnosis of drug-induced valvular heart disease in patients previously exposed to benfluorex: a prospective multicentre study.

PubMed

Maréchaux, Sylvestre; Rusinaru, Dan; Jobic, Yannick; Ederhy, Stéphane; Donal, Erwan; Réant, Patricia; Arnalsteen, Elise; Boulanger, Jacques; Garban, Thierry; Ennezat, Pierre-Vladimir; Jeu, Antoine; Szymanski, Catherine; Tribouilloy, Christophe

2015-02-01

The Food and Drug Administration (FDA) criteria for diagnosis of drug-induced valvular heart disease (DIVHD) are only based on the observation of aortic regurgitation ≥ mild and/or mitral regurgitation ≥ moderate. We sought to evaluate the diagnostic value of FDA criteria in a cohort of control patients and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD. This prospective, multicentre study included 376 diabetic control patients not exposed to valvulopathic drugs and 1000 subjects previously exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a combined functional and morphological echocardiographic analysis of cardiac valves. Patients were classified according to the FDA criteria [mitral or aortic-FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the 910 patients (99%) without a diagnosis of the mitral DIVHD group were classified as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were independent predictors of disagreement between FDA criteria and the diagnosis of DIVHD in patients exposed to benfluorex (both P ≤ 0.001). FDA criteria solely based on the Doppler detection of cardiac valve regurgitation underestimate for the mitral valve and overestimate for the aortic valve the frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined echocardiographic and Doppler morphological and functional analysis of cardiac valves. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Considering the Future of Pharmaceutical Promotions in Social Media Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

PubMed

Carpentier, Francesca Renee Dillman

2016-02-09

This commentary explores the implications of increased social media marketing by drug manufacturers, based on findings in Hyosun Kim's article of the major themes in recent Food and Drug Administration (FDA) warning letters and notices of violation regarding online direct-to-consumer promotions of pharmaceuticals. Kim's rigorous analysis of FDA letters over a 10-year span highlights a relative abundance of regulatory action toward marketer-controlled websites and sponsored advertisements, compared to branded and unbranded social media messaging. However, social media marketing efforts are increasing, as is FDA attention to these efforts. This commentary explores recent developments and continuing challenges in the FDA's attempts to provide guidance and define pharmaceutical company accountability in marketer-controlled and -uncontrolled claims disseminated through social media. © 2016 by Kerman University of Medical Sciences.

Investigation of the interfacial reaction between metal and fluorine-contained polyimides

NASA Astrophysics Data System (ADS)

Yang, Ching-Yu; Chen, J. S.; Hsu, S. L. C.

2005-07-01

In this work, thin metal films (Cr and Ta) were deposited on fluorine-contained polyimides, 6FDA-BisAAF, and 6FDA-PPD. The chemical states of the metal/polyimide samples were characterized by using x-ray photoelectron spectroscopy (XPS). XPS analysis reveals that metal-C, C-O, and metal-O bondings are present in metallized 6FDA-BisAAF and 6FDA-PPD. C-F bonds are observed in bare 6FDA-BisAAF and 6FDA-PPD however, they are not seen in the metallized samples. Disappearance of the C-F bonding is attributed to the disruption of CF3 side groups from the main chains of 6FDA-BisAAF and 6FDA-PPD when the chains are exposed to the plasma during the metal deposition. Nevertheless, the disruption of CF3 side groups also creates sites for the formation of metal-C or C-O bondings, which provide a positive adhesion strength at the metal/polyimide interface, as revealed by the tape test.

Generalized Partial Least Squares Approach for Nominal Multinomial Logit Regression Models with a Functional Covariate

ERIC Educational Resources Information Center

Albaqshi, Amani Mohammed H.

2017-01-01

Functional Data Analysis (FDA) has attracted substantial attention for the last two decades. Within FDA, classifying curves into two or more categories is consistently of interest to scientists, but multi-class prediction within FDA is challenged in that most classification tools have been limited to binary response applications. The functional…

Patient Experience Data in US Food and Drug Administration (FDA) Regulatory Decision Making:: A Policy Process Perspective.

PubMed

Kuehn, Carrie M

2018-01-01

The influence of patient advocates on FDA regulatory decision making has increased. Despite enhanced engagement with FDA, there remain challenges to achieving the regulatory goals of patients within FDA's regulatory framework. Gaps exist between patient advocates' knowledge of the agency's processes and FDA's need for rigorous, clinically meaningful patient experience data. This study examined the policy process in which patient experience data are collected by patient advocates and provided to FDA for regulatory decision making. Semistructured, narrative interviews were conducted with 14 professionals working in patient advocacy or at FDA. The purpose was to examine, in depth, participants' perceptions and experiences regarding this new regulatory process. Interviews were coded and examined for themes. The use of patient experience data by FDA is an evolving regulatory process. Participants identified a number of barriers and contributors to regulatory success. Well-organized and sophisticated patient advocacy groups with access to scientific and policy expertise are more likely to find success meeting FDA's patient experience data requirements. A conceptual model of this regulatory process was developed. Use of patient experience data by FDA has the potential to positively influence the regulation of medical products in the United States. Success within this new regulatory process will depend on clear guidance from FDA regarding the collection, analysis, and use of patient experience data. Patient advocacy groups must enhance internal capacity and expertise while engaging in substantive collaborations with FDA and other stakeholders in order to meaningfully contribute to the regulatory review of new therapeutics.

FDA Bacteriological Analytical Manual, Chapter 10, 2003: Listeria monocytogenes

EPA Pesticide Factsheets

FDA Bacteriological Analytical Manual, Chapter 10 describes procedures for analysis of food samples and may be adapted for assessment of solid, particulate, aerosol, liquid and water samples containing Listeria monocytogenes.

Cigarette Graphic Warning Labels and Smoking Prevalence in Canada: A Critical Examination and Reformulation of the FDA Regulatory Impact Analysis

PubMed Central

Huang, Jidong; Chaloupka, Frank J.; Fong, Geoffrey T.

2014-01-01

Background The estimated effect of cigarette graphic warning labels (GWLs) on smoking rates is a key input to FDA's regulatory impact analysis (RIA), required by law as part of its rulemaking process. However, evidence on the impact of GWLs on smoking prevalence is scarce. Objective The goal of this paper is to critically analyze FDA's approach to estimating the impact of GWLs on smoking rates in its RIA, and to suggest a path forward to estimating the impact of the adoption of GWLs in Canada on Canadian national adult smoking prevalence. Methods A quasi-experimental methodology was employed to examine the impact of adoption of GWLs in Canada in 2000, using the U.S. as a control. Findings We found a statistically significant reduction in smoking rates after the adoption of GWLs in Canada in comparison to the U.S. Our analyses show that implementation of GWLs in Canada reduced smoking rates by 2.87 to 4.68 percentage points, a relative reduction of 12.1 to 19.6% — 33 to 53 times larger than FDA's estimates of a 0.088 percentage point reduction. We also demonstrated that FDA's estimate of the impact was flawed because it is highly sensitive to the changes in variable selection, model specification, and the time period analyzed. Conclusions Adopting GWLs on cigarette packages reduces smoking prevalence. Applying our analysis of the Canadian GWLs, we estimate that if the U.S. had adopted GWLs in 2012, the number of adult smokers in the U.S. would have decreased by 5.3 to 8.6 million in 2013. Our analysis demonstrates that FDA's approach to estimating the impact of GWLs on smoking rates is flawed. Rectifying these problems before this approach becomes the norm is critical for FDA's effective regulation of tobacco products. PMID:24218057

Language and Nutrition (Mis)Information: Food Labels, FDA Policies and Meaning

ERIC Educational Resources Information Center

Taylor, Christy Marie

2013-01-01

In this dissertation, I address the ways in which food manufacturers can exploit the often vague and ambiguous nature of FDA policies concerning language and images used on food labels. Employing qualitative analysis methods (Strauss, 1987; Denzin and Lincoln, 2003; Mackey and Gass, 2005) that drew upon critical discourse analysis (Fairclough,…

General administrative rulings and decisions; amendment to the examination and investigation sample requirements; companion document to direct final rule--FDA. Proposed rule.

PubMed

1998-09-25

The Food and Drug Administration (FDA) is proposing to amend its regulations regarding the collection of twice the quantity of food, drug, or cosmetic estimated to be sufficient for analysis. This action increases the dollar amount that FDA will consider to determine whether to routinely collect a reserve sample of a food, drug, or cosmetic product in addition to the quantity sufficient for analysis. Experience has demonstrated that the current dollar amount does not adequately cover the cost of most quantities sufficient for analysis plus reserve samples. This proposed rule is a companion to the direct final rule published elsewhere in this issue of the Federal Register. This action is part of FDA's continuing effort to achieve the objectives of the President's "Reinventing Government" initiative, and it is intended to reduce the burden of unnecessary regulations on food, drugs, and cosmetics without diminishing the protection of the public health.

Examining the FDA's oversight of direct-to-consumer advertising.

PubMed

Gahart, Martin T; Duhamel, Louise M; Dievler, Anne; Price, Roseanne

2003-01-01

Our analysis examined the effects of the Food and Drug Administration's (FDA's) 1997 draft guidance regarding advertisements for prescription drugs broadcast directly to consumers. We found that although direct-to-consumer (DTC) advertising spending by pharmaceutical companies has increased, more than 80 percent of their promotional spending is directed to physicians. DTC advertising appears to increase the use of prescription drugs among consumers. The FDA's oversight has not prevented companies from making misleading claims in subsequent advertisements, and a recent policy change has lengthened the FDA's review process, raising the possibility that some misleading campaigns could run their course before review.

Stimulated reporting: the impact of US food and drug administration-issued alerts on the adverse event reporting system (FAERS).

PubMed

Hoffman, Keith B; Demakas, Andrea R; Dimbil, Mo; Tatonetti, Nicholas P; Erdman, Colin B

2014-11-01

The US Food and Drug Administration (FDA) uses the Adverse Event Reporting System (FAERS) to support post-marketing safety surveillance programs. Currently, almost one million case reports are submitted to FAERS each year, making it a vast repository of drug safety information. Sometimes cited as a limitation of FAERS, however, is the assumption that "stimulated reporting" of adverse events (AEs) occurs in response to warnings, alerts, and label changes that are issued by the FDA. To determine the extent of "stimulated reporting" in the modern-day FAERS database. One hundred drugs approved by the FDA between 2001 and 2010 were included in this analysis. FDA alerts were obtained by a comprehensive search of the FDA's MedWatch and main websites. Publicly available FAERS data were used to assess the "primary suspect" AE reporting pattern for up to four quarters before, and after, the issuance of an FDA alert. A few drugs did demonstrate "stimulated reporting" trends. A majority of the drugs, however, showed little evidence for significant reporting changes associated with the issuance of alerts. When we compared the percentage changes in reporting after an FDA alert with those after a sham "control alert", the overall reporting trends appeared to be quite similar. Of 100 drugs analyzed for short-term reporting trends, 21 real alerts and 25 sham alerts demonstrated an increase (greater than or equal to 1 %) in reporting. The long-term analysis of 91 drugs showed that 24 real alerts and 28 sham alerts demonstrated a greater than or equal to 1 % increase. Our results suggest that most of modern day FAERS reporting is not significantly affected by the issuance of FDA alerts.

Alternative methods to determine headwater benefits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bao, Y.S.; Perlack, R.D.; Sale, M.J.

1997-11-10

In 1992, the Federal Energy Regulatory Commission (FERC) began using a Flow Duration Analysis (FDA) methodology to assess headwater benefits in river basins where use of the Headwater Benefits Energy Gains (HWBEG) model may not result in significant improvements in modeling accuracy. The purpose of this study is to validate the accuracy and appropriateness of the FDA method for determining energy gains in less complex basins. This report presents the results of Oak Ridge National Laboratory`s (ORNL`s) validation of the FDA method. The validation is based on a comparison of energy gains using the FDA method with energy gains calculatedmore » using the MWBEG model. Comparisons of energy gains are made on a daily and monthly basis for a complex river basin (the Alabama River Basin) and a basin that is considered relatively simple hydrologically (the Stanislaus River Basin). In addition to validating the FDA method, ORNL was asked to suggest refinements and improvements to the FDA method. Refinements and improvements to the FDA method were carried out using the James River Basin as a test case.« less

Food and Drug Administration: Insufficient Planning for Field Laboratory Consolidation Decisions.

DTIC Science & Technology

1987-12-04

adequately 5 address whether FDA could meet its current and future laboratory needs if the five laboratories were closed or whether cost- effective ...pie transit and laboratory processing times would lessen FDA’S regula- tory effectiveness . Moreover, 61 percent of the excess laboratory capacity...FDA believes that it can ship sam- pies from across the nation to almost any location for analysis without reducing its regulatory effectiveness . (See

A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Multiple Myeloma.

PubMed

Raju, G K; Gurumurthi, Karthik; Domike, Reuben; Kazandjian, Dickran; Landgren, Ola; Blumenthal, Gideon M; Farrell, Ann; Pazdur, Richard; Woodcock, Janet

2018-01-01

Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analysis. In this work, a quantitative benefit-risk analysis approach captures regulatory decision-making about new drugs to treat multiple myeloma (MM). MM assessments have been based on endpoints such as time to progression (TTP), progression-free survival (PFS), and objective response rate (ORR) which are different than benefit-risk analysis based on overall survival (OS). Twenty-three FDA decisions on MM drugs submitted to FDA between 2003 and 2016 were identified and analyzed. The benefits and risks were quantified relative to comparators (typically the control arm of the clinical trial) to estimate whether the median benefit-risk was positive or negative. A sensitivity analysis was demonstrated using ixazomib to explore the magnitude of uncertainty. FDA approval decision outcomes were consistent and logical using this benefit-risk framework. © 2017 American Society for Clinical Pharmacology and Therapeutics.

The Pharmaceutical Industry in 2016. An Analysis of FDA Drug Approvals from a Perspective of the Molecule Type.

PubMed

Torre, Beatriz G de la; Albericio, Fernando

2017-02-27

This is an analysis from a chemical point of view of the 22 drugs accepted by the FDA during 2016. The different drugs from the 2016 "harvest" have been classified according to their chemical structure: antibodies; TIDES (oligonucleotides and peptides); amino acids and natural products; drug combination; and small molecules.

NHEXAS PHASE I ARIZONA STUDY--STANDARD OPERATING PROCEDURE--COMPENDIUM OF METHODS FOR ANALYSIS OF TRACE METALS AND PESTICIDES IN DIETARY SAMPLES USING TOTAL DIET STUDY PROCEDURES (FDA-COMPENDIUM)

EPA Science Inventory

This compendium contains seven SOPs developed by Food and Drug Administration (FDA) laboratories for methods of analyzing trace metals in dietary samples collected using Total Diet study procedures. The SOPs include the following: (1) Quality Control for Analysis of NHEXAS Food o...

Development and Validation of New Discriminative Dissolution Method for Carvedilol Tablets

PubMed Central

Raju, V.; Murthy, K. V. R.

2011-01-01

The objective of the present study was to develop and validate a discriminative dissolution method for evaluation of carvedilol tablets. Different conditions such as type of dissolution medium, volume of dissolution medium and rotation speed of paddle were evaluated. The best in vitro dissolution profile was obtained using Apparatus II (paddle), 50 rpm, 900 ml of pH 6.8 phosphate buffer as dissolution medium. The drug release was evaluated by high-performance liquid chromatographic method. The dissolution method was validated according to current ICH and FDA guidelines using parameters such as the specificity, accuracy, precision and stability were evaluated and obtained results were within the acceptable range. The comparison of the obtained dissolution profiles of three different products were investigated using ANOVA-based, model-dependent and model-independent methods, results showed that there is significant difference between the products. The dissolution test developed and validated was adequate for its higher discriminative capacity in differentiating the release characteristics of the products tested and could be applied for development and quality control of carvedilol tablets. PMID:22923865

A brave new beef: The US Food and Drug Administration's review of the safety of cloned animal products.

PubMed

Solomon, Louis M; Noll, Rebekka C; Mordkoff, David S; Murphy, Patrick; Rolerson, Marcy

2009-09-01

To meet its public mandate, the US Food and Drug Administration (FDA) collected studies on the potential health hazards of eating or drinking cloned food products. Based on an earlier National Academy of Sciences study that, on closer analysis, was not nearly as sanguine, the FDA's report found no evidence of a health risk from the public's ingestion of cloned food products. This article analyzes the risks the FDA considered, and concludes that there is a disconnect between the risks the FDA assessed in these studies and the risks that might arise from cloned food products. The FDA should consider instituting effective tracking mechanisms and other diagnostics that would permit scientists and the public to answer the question of health risks posed by cloned food products.

Public voices in pharmaceutical deliberations: negotiating "clinical benefit" in the FDA's Avastin Hearing.

PubMed

Teston, Christa B; Graham, S Scott; Baldwinson, Raquel; Li, Andria; Swift, Jessamyn

2014-06-01

This article offers a hybrid rhetorical-qualitative discourse analysis of the FDA's 2011 Avastin Hearing, which considered the revocation of the breast cancer indication for the popular cancer drug Avastin. We explore the multiplicity of stakeholders, the questions that motivated deliberations, and the kinds of evidence presented during the hearing. Pairing our findings with contemporary scholarship in rhetorical stasis theory, Mol's (2002) construct of multiple ontologies, and Callon, Lascoumes, and Barthe's (2011) "hybrid forums," we demonstrate that the FDA's deliberative procedures elides various sources of evidence and the potential multiplicity of definitions for "clinical benefit." Our findings suggest that while the FDA invited multiple stakeholders to offer testimony, there are ways that the FDA might have more meaningfully incorporated public voices in the deliberative process. We conclude with suggestions for how a true hybrid forum might be deployed.

Characteristics of FDA drug recalls: A 30-month analysis.

PubMed

Hall, Kelsey; Stewart, Tyler; Chang, Jongwha; Freeman, Maisha Kelly

2016-02-15

The characteristics of drug recalls issued over 30 months by the Food and Drug Administration (FDA) were analyzed. All FDA-issued recalls for drugs (prescription and nonprescription, including dietary supplements) and biological products issued from June 20, 2012, to December 31, 2014, were included in this retrospective analysis. Data for all drug recalls were downloaded and sorted by the inclusion criteria from weekly FDA enforcement reports. The following data were analyzed: product type, recall firm, type of recall firm (compounding or noncompounding), country, voluntary or involuntary recall, method of communication of recall, recall number, FDA recall classification (class I, II, or III), product availability (prescription or nonprescription), reason for recall, recall initiation date, and recall report date. A total of 21,120 products were recalled during the 30-month study period. Of these, 3,045 drug products (14.4%) met the inclusion criteria and were analyzed. A total of 348 total manufacturers were associated with recalled drug products. The 5 firms most frequently involved in recalls accounted for 299, 273, 212, 118, and 112 recalls. The most common reasons for recalls were contamination, mislabeling, adverse reaction, defective product, and incorrect potency. There was a significant association between FDA recall classification and the following outcomes: reasons for recall, product availability, type of recall firm, and form of communication. An investigation of FDA drug recalls revealed that the five most common recall reasons were contamination, mislabeling, adverse reaction, defective product, and incorrect potency. Compounding firms were associated more frequently with contamination than were noncompounding firms. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

A comparison of new drugs approved by the FDA, the EMA, and Swissmedic: an assessment of the international harmonization of drugs.

PubMed

Zeukeng, Minette-Joëlle; Seoane-Vazquez, Enrique; Bonnabry, Pascal

2018-06-01

This study compared the characteristics of new human drugs approved by the Food and Drug Administration (FDA), the European Medicine Agency (EMA), and Swissmedic (SMC) in the period 2007 to 2016. The list of new drugs and therapeutic biologics approved by the FDA, the EMA, and SMC in the period 2007 to 2016 was collected from websites of those agencies. The study included regulatory information, approval date, and indication for each drug. Descriptive statistical t tests and x 2 -tests were performed for the analysis. From 2007 to 2016, 134 new drugs were approved by all three regulatory agencies. Overall, 66.4% of the drugs were first approved by the FDA, 30.6% by the EMA, and 3.0% by SMC. The difference in approval dates between SMC and the EMA, SMC and the FDA, and the FDA and the EMA were statistically significant. The indications approved by the FDA, the EMA, and SMC for the same drugs were similar in content for 23.1% drugs and different in 76.9% of the drugs. Significant differences in indications existed between the FDA and SMC and the FDA and the EMA, but not between the EMA and SMC. There were differences in the characteristics of new drugs approved by the EMA, the FDA, and SMC in the period 2007-2016. Overall, two thirds of the new drugs were first approved by the FDA. Differences in indications were found in three out of four new drugs approved by the three regulatory agencies. Despite international drug regulation harmonization efforts, significant differences in the characteristics of new drugs approved by different agencies persist.

The history and contemporary challenges of the US Food and Drug Administration.

PubMed

Borchers, Andrea T; Hagie, Frank; Keen, Carl L; Gershwin, M Eric

2007-01-01

The year 2006 marks the 100th anniversary of the regulatory agency now known as the US Food and Drug Administration (FDA), the first consumer protection agency of the federal government and arguably the most influential regulatory agency in the world. The FDA thus plays an integral role in the use of pharmaceuticals, not only in the United States but worldwide. The goal of this review was to present an overview of the FDA and place its current role in the perspectives of history and contemporary needs. Relevant materials for this review were identified through a search of the English-language literature indexed on MEDLINE (through 2006) using the main search terms United States Food and Drug Administration, FDA, history of the FDA, drug approvals, drug legislation, and FDA legislation. Results from the initial searches were then explored further. The statute that created the bureau which later became the FDA established this agency to prohibit interstate commerce of adulterated foods, drinks, and drugs. The Food, Drug, and Cosmetic Act that replaced it in 1938, and subsequent food and drug laws and amendments, expanded the FDA's responsibilities to cosmetics, medical devices, biological products, and radiation-emitting products. These amendments have also established the FDA as a mainly preventive regulatory agency that relies chiefly on pre-market control. As such, the FDA has played an important role in shaping the modern pharmaceutical industry by making the scientific approach and the clinical trial process the standard for establishing safety and efficacy and by making rigorous scientific analysis the predominant component of the process for pharmaceutical regulation. As shown in this review, the evolution of the FDA can be described as a series of "crisis-legislation-adaptation" cycles: a public health crisis promoted the passage of congressional legislation, which was then followed by implementation of the law by the FDA. However, the crises the FDA faces currently are likely to be overcome only under strong and permanent leadership willing to redefine the role and procedures of the FDA with an open mind.

FDA's Flexibility in Subpart H Approvals: Assessing Quantum of Effectiveness Evidence.

PubMed

Sasinowski, Frank J; Varond, Alexander J

2016-08-01

This article examines the strength of scientific and clinical evidence for FDA's nineteen non-AIDS, non-cancer Subpart H approval determinations over the Accelerated Approval program's twenty-four year existence. The authors researched the bases for FDA's determinations when an unvalidated surrogate or intermediate clinical endpoint is "reasonably likely to predict clinical benefit." The four key factors set forth in FDA's "Guidance for Industry, Expedited Programs for Serious Conditions - Drugs and Biologics" were applied to past Subpart H approvals. For the nineteen precedents, the authors found wide variances between the quantum and quality of evidence on each of the four factors, indicating that a lack of evidence on any single factor was not disqualifying in and of itself. The results of this study, therefore, show that FDA exercises extraordinarily more regulatory flexibility than either FDA's foundational statutes or even FDA' s most recent 2014 Expedited Programs Guidance explicitly express. Given recent legislative exhortations and the increasing promise of personalized medicine and translational sciences, the authors conclude that Subpart H should be further explored and utilized. The authors provide a detailed analysis of the orecedents established in the nineteen approvals.

The Food and Drug Administration reports provided more data but were more difficult to use than the European Medicines Agency reports.

PubMed

Schroll, Jeppe Bennekou; Abdel-Sattar, Maher; Bero, Lisa

2015-01-01

To compare the accessibility, comprehensiveness, and usefulness of data available from the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) drug reports. This is a cross-sectional study. All new molecular drugs approved between January 1, 2011 and December 31, 2012 from the FDA and EMA Web sites were eligible. We included 27 drug reports. Most were searchable, but the FDA table of contents did not match the file's page numbers. Several FDA documents must be searched compared with a single EMA document, but the FDA reports contain more summary data on harms. Detailed information about harms was reported for 93% of the FDA reports (25 of 27 reports) and 26% of the EMA reports (7 of 27 reports). The reports contained information about trial methodology but did not include trial registry IDs or investigator names. All reports but one contained sufficient information to be used in a meta-analysis. Detailed data on efficacy and harms are available at the two agencies. The FDA has more summary data on harms, but the documents are harder to navigate. Published by Elsevier Inc.

Comparison of Unlicensed and Off-Label Use of Antipsychotics Prescribed to Child and Adolescent Psychiatric Outpatients for Treatment of Mental and Behavioral Disorders with Different Guidelines: The China Food and Drug Administration Versus the FDA.

PubMed

Zhu, Xiuqing; Hu, Jinqing; Sun, Bin; Deng, Shuhua; Wen, Yuguan; Chen, Weijia; Qiu, Chang; Shang, Dewei; Zhang, Ming

2018-04-01

This study aims to compare the prevalence of unlicensed and off-label use of antipsychotics among child and adolescent psychiatric outpatients with guidelines proposed by the China Food and Drug Administration (CFDA) and the U.S. Food and Drug Administration (FDA), and to identify factors associated with inconsistencies between the two regulations. A retrospective analysis of 29,326 drug prescriptions for child and adolescent outpatients from the Affiliated Brain Hospital of Guangzhou Medical University was conducted. Antipsychotics were classified as "unlicensed" or "off-label use" according to the latest pediatric license information registered by the CFDA and the FDA or the package inserts of antipsychotics authorized by the CFDA or the FDA for the treatment of pediatric mental and behavioral disorders, respectively. Binary logistic regression analysis was performed to assess factors associated with inconsistencies between the two regulations. The total unlicensed use, according to the CFDA analysis, was higher than that found in the FDA analysis (74.14% vs. 22.04%, p < 0.001). However, the total off-label use, according to the FDA analysis, was higher than that found in the CFDA analysis (46.53% vs. 15.77%, p < 0.001). Antipsychotic drug classes, age group, number of diagnoses, and diagnosis of schizophrenia and schizotypal and delusional disorders were associated with inconsistent unlicensed use. Antipsychotic drug classes, age group, number of prescribed psychotropic drugs, gender, diagnosis of schizophrenia and schizotypal and delusional disorders, diagnosis of mood [affective] disorders, diagnosis of mental retardation, and diagnosis of psychological development disorders were associated with inconsistent off-label use. The difference in prevalence of total unlicensed and off-label use of antipsychotics between the two regulations was statistically significant. This inconsistency could be partly attributed to differences in pediatric license information and package inserts of antipsychotics. The results indicate a need for further clinical pediatric studies and better harmonization between agencies regarding antipsychotic used in pediatrics.

21 CFR 54.1 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-04-01

... steps have not been taken in the design, conduct, reporting, and analysis of the studies to minimize... INVESTIGATORS § 54.1 Purpose. (a) The Food and Drug Administration (FDA) evaluates clinical studies submitted in... clinical studies to determine whether the applications are approvable under the statutory requirements. FDA...

21 CFR 54.1 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-04-01

... steps have not been taken in the design, conduct, reporting, and analysis of the studies to minimize... INVESTIGATORS § 54.1 Purpose. (a) The Food and Drug Administration (FDA) evaluates clinical studies submitted in... clinical studies to determine whether the applications are approvable under the statutory requirements. FDA...

Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies

PubMed Central

Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

2017-01-01

Objectives To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Design Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data sources Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Outcome measures Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. Results The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%–100%) of trials in patients were registered, 71% (IQR 57%–100%) reported results or shared a CSR synopsis, 80% (70%–100%) were published and 96% (80%–100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%–100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Conclusions Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies’ transparency records and recognise exemplary companies may encourage further progress. PMID:29208616

How drugs are developed and approved by the FDA: current process and future directions.

PubMed

Ciociola, Arthur A; Cohen, Lawrence B; Kulkarni, Prasad

2014-05-01

This article provides an overview of FDA's regulatory processes for drug development and approval, and the estimated costs associated with the development of a drug, and also examines the issues and challenges facing the FDA in the near future. A literature search was performed using MEDLINE to summarize the current FDA drug approval processes and future directions. MEDLINE was further utilized to search for all cost analysis studies performed to evaluate the pharmaceutical industry R&D productivity and drug development cost estimates. While the drug approval process remains at high risk and spans over multiple years, the FDA drug review and approval process has improved, with the median approval time for new molecular drugs been reduced from 19 months to 10 months. The overall cost to development of a drug remains quite high and has been estimated to range from $868M to $1,241M USD. Several new laws have been enacted, including the FDA Safety and Innovation Act (FDASIA) of 2013, which is designed to improve the drug approval process and enhance access to new medicines. The FDA's improved processes for drug approval and post-market surveillance have achieved the goal of providing patients with timely access to effective drugs while minimizing the risk of drug-related harm. The FDA drug approval process is not without controversy, as a number of well-known gastroenterology drugs have been withdrawn from the US market over the past few years. With the approval of the new FDASIA law, the FDA will continue to improve their processes and, working together with the ACG through the FDA-Related Matters Committee, continue to develop safe and effective drugs for our patients.

Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: Teaching Drug Marketers How to Inform Better or Spin Better? Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

PubMed

Doran, Evan

2016-02-21

Hyosun Kim's report "Trouble Spots in Online Direct to Consumer Prescription Drug Promotion: A content Analysis of FDA Warning Letters" aims to teach marketers how to avoid breaching current Food and Drug Administration (FDA) guidelines in their online drug promotion. While Kim hopes to minimise the potential for online promotion to misinform consumers and the study is carefully conducted, teaching drug marketers how to avoid the common mistakes in online drug promotion is more likely to make marketers more adept at spinning information than appropriately balancing it. © 2016 by Kerman University of Medical Sciences.

Adherence of Pharmaceutical Advertisements in Medical Journals to FDA Guidelines and Content for Safe Prescribing

PubMed Central

Korenstein, Deborah; Keyhani, Salomeh; Mendelson, Ali; Ross, Joseph S.

2011-01-01

Background Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA); adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing. Methods and Findings Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U.S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1–14). Six “teaser” advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1%) adhered to all FDA guidelines, 41 (49.4%) were non-adherent with at least one form of FDA-described bias, and 27 (32.5%) were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence. Conclusions Few physician-directed print pharmaceutical advertisements adhere to all FDA guidelines; over half fail to quantify serious risks. The FDA could better protect public health by creating new more objective advertisement guidelines requiring transparent presentation of basic safety and efficacy information. PMID:21858076

Adherence of pharmaceutical advertisements in medical journals to FDA guidelines and content for safe prescribing.

PubMed

Korenstein, Deborah; Keyhani, Salomeh; Mendelson, Ali; Ross, Joseph S

2011-01-01

Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA); adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing. Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U.S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1-14). Six "teaser" advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1%) adhered to all FDA guidelines, 41 (49.4%) were non-adherent with at least one form of FDA-described bias, and 27 (32.5%) were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence. Few physician-directed print pharmaceutical advertisements adhere to all FDA guidelines; over half fail to quantify serious risks. The FDA could better protect public health by creating new more objective advertisement guidelines requiring transparent presentation of basic safety and efficacy information.

78 FR 69689 - Agency Information Collection Activities; Proposed Collection; Comment Request; Hazard Analysis...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-1427... Critical Control Point Procedures for the Safe and Sanitary Processing and Importing of Juice AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

Advocacy for Gender Affirming Care: Learning from the Injectable Estrogen Shortage.

PubMed

Geffen, Sophia; Horn, Tim; Smith, Kimberleigh Joy; Cahill, Sean

2018-01-01

Hormone therapy is medically necessary for many transgender individuals. The U.S. Food and Drug Administration (FDA) and pharmaceutical companies' failure to guarantee a supply of injectable estrogen in 2016 and 2017 for transgender individuals is a violation of their right to comprehensive medical treatment, free of discrimination. A series of advocacy actions eventually led to all formulations of injectable estrogen being restored to market; however, long-term solutions to supply interruptions of injectable estrogen are needed. Long-term solutions should address the lack of federally funded research and, consequently, evidence-based practice on hormone therapy for gender affirmation.

Scouting For Approval: Lessons on Medical Device Regulation in an Era of Crowdfunding from Scanadu's "Scout".

PubMed

Smith, Colleen

2015-01-01

Internet crowdfunding, a new and increasingly popular method of raising capital to develop products and businesses, has recently come into conflict with the Food and Drug Administration's (FDA's) regulation of medical devices. This Article examines the issues that arise when companies pre-sell medical devices via crowdfunding campaigns before gaining FDA approval of the devices. Because Internet crowdfunding has only been in use for a few years, little has been written about it academically, particularly about its interaction with FDA regulations. The rising interest in crowdfunding, coupled with the downturn in investment in the American medical device industry, make this a salient issue that is ripe for FDA review. This Article uses the crowdfunding campaign Scanadu, a medical device company, conducted in 2013 to raise money to develop its in-home diagnostic device, the "Scout," as a starting point for this analysis. Because it is extremely costly to develop a device and obtain FDA approval, medical device companies should be able to utilize crowdfunding to raise the necessary capital. However, because of the possible dangers medical devices pose, FDA needs to review the risks created by allowing companies to crowdfund medical devices and should issue guidance to help companies comply with FDA regulations while still allowing them to take advantage of the benefits of crowdfunding. This guidance should ensure the continued commitment to consumer safety that is at the core of FDA regulation.

Food and Drug Administration tobacco regulation and product judgments.

PubMed

Kaufman, Annette R; Finney Rutten, Lila J; Parascandola, Mark; Blake, Kelly D; Augustson, Erik M

2015-04-01

The Family Smoking Prevention and Tobacco Control Act granted the Food and Drug Administration (FDA) the authority to regulate tobacco products in the U.S. However, little is known about how regulation may be related to judgments about tobacco product-related risks. To understand how FDA tobacco regulation beliefs are associated with judgments about tobacco product-related risks. The Health Information National Trends Survey is a national survey of the U.S. adult population. Data used in this analysis were collected from October 2012 through January 2013 (N=3,630) by mailed questionnaire and analyzed in 2013. Weighted bivariate chi-square analyses were used to assess associations among FDA regulation belief, tobacco harm judgments, sociodemographics, and smoking status. A weighted multinomial logistic regression was conducted where FDA regulation belief was regressed on tobacco product judgments, controlling for sociodemographic variables and smoking status. About 41% believed that the FDA regulates tobacco products in the U.S., 23.6% reported the FDA does not, and 35.3% did not know. Chi-square analyses showed that smoking status was significantly related to harm judgments about electronic cigarettes (p<0.0001). The multinomial logistic regression revealed that uncertainty about FDA regulation was associated with tobacco product harm judgment uncertainty. Tobacco product harm perceptions are associated with beliefs about tobacco product regulation by the FDA. These findings suggest the need for increased public awareness and understanding of the role of tobacco product regulation in protecting public health. Copyright © 2015. Published by Elsevier Inc.

Raman spectral analysis for rapid screening of dengue infection

NASA Astrophysics Data System (ADS)

Mahmood, T.; Nawaz, H.; Ditta, A.; Majeed, M. I.; Hanif, M. A.; Rashid, N.; Bhatti, H. N.; Nargis, H. F.; Saleem, M.; Bonnier, F.; Byrne, H. J.

2018-07-01

Infection with the dengue virus is currently clinically detected according to different biomarkers in human blood plasma, commonly measured by enzyme linked immunosorbent assays, including non-structural proteins (Ns1), immunoglobulin M (IgM) and immunoglobulin G (IgG). However, there is little or no mutual correlation between the biomarkers, as demonstrated in this study by a comparison of their levels in samples from 17 patients. As an alternative, the label free, rapid screening technique, Raman spectroscopy has been used for the characterisation/diagnosis of healthy and dengue infected human blood plasma samples. In dengue positive samples, changes in specific Raman spectral bands associated with lipidic and amino acid/protein content are observed and assigned based on literature and these features can be considered as markers associated with dengue development. Based on the spectroscopic analysis of the current, albeit limited, cohort of samples, Principal Components Analysis (PCA) coupled Factorial Discriminant Analysis, yielded values of 97.95% sensitivity and 95.40% specificity for identification of dengue infection. Furthermore, in a comparison of the normal samples to the patient samples which scored low for only one of the biomarker tests, but high or medium for either or both of the other two, PCA-FDA demonstrated a sensitivity of 97.38% and specificity of 86.18%, thus providing an unambiguous screening technology.

Enrollment and Monitoring of Women in Post-Approval Studies for Medical Devices Mandated by the Food and Drug Administration

PubMed Central

Herz, Naomi; Loyo-Berrios, Nilsa; Tarver, Michelle

2014-01-01

Abstract Background: Disease presentation, prevalence, and treatment effects vary by sex, thus it is important to ensure adequate participation of both sexes in medical device post-approval studies (PAS). Methods: The goals of this study were to determine the participation rate of women in PAS mandated by the Food and Drug Administration (FDA) and if participation varied by clinical area. The study also evaluated the frequency in which enrollment by sex is reported by applicant reports and FDA reviews, as well as the frequency in which final study reports analyze whether outcomes differ by sex. Results: Of 89 studies with enrollment completed, data on sex of participants were available in 93% of submitted reports, while data on enrollment by sex was evaluated and noted in 43% of FDA review memos. Study participation varied by clinical area, with female participation ranging from 32% in cardiovascular PAS to 90% in PAS for reconstructive devices. Of 53 completed studies, data on enrollment by sex was provided in 49 of the final reports. Of these 14% included a multivariate analysis that included sex as a covariate and 4% included a subgroup analysis for female participants. Conclusions: Data on sex was not routinely assessed in FDA reviews. Based on these findings, FDA implemented new procedures to ensure participation by sex is evaluated in PAS reviews. FDA will continue working with applicants to develop PAS that enroll and retain proportions of women consistent with the sex-specific prevalence for the disease or condition the device is used to treat. PMID:24405314

New era in drug interaction evaluation: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process.

PubMed

Huang, Shiew-Mei; Strong, John M; Zhang, Lei; Reynolds, Kellie S; Nallani, Srikanth; Temple, Robert; Abraham, Sophia; Habet, Sayed Al; Baweja, Raman K; Burckart, Gilbert J; Chung, Sang; Colangelo, Philip; Frucht, David; Green, Martin D; Hepp, Paul; Karnaukhova, Elena; Ko, Hon-Sum; Lee, Jang-Ik; Marroum, Patrick J; Norden, Janet M; Qiu, Wei; Rahman, Atiqur; Sobel, Solomon; Stifano, Toni; Thummel, Kenneth; Wei, Xiao-Xiong; Yasuda, Sally; Zheng, Jenny H; Zhao, Hong; Lesko, Lawrence J

2008-06-01

Predicting clinically significant drug interactions during drug development is a challenge for the pharmaceutical industry and regulatory agencies. Since the publication of the US Food and Drug Administration's (FDA's) first in vitro and in vivo drug interaction guidance documents in 1997 and 1999, researchers and clinicians have gained a better understanding of drug interactions. This knowledge has enabled the FDA and the industry to progress and begin to overcome these challenges. The FDA has continued its efforts to evaluate methodologies to study drug interactions and communicate recommendations regarding the conduct of drug interaction studies, particularly for CYP-based and transporter-based drug interactions, to the pharmaceutical industry. A drug interaction Web site was established to document the FDA's current understanding of drug interactions (http://www.fda.gov/cder/drug/drugInteractions/default.htm). This report provides an overview of the evolution of the drug interaction guidances, includes a synopsis of the steps taken by the FDA to revise the original drug interaction guidance documents, and summarizes and highlights updated sections in the current guidance document, Drug Interaction Studies-Study Design, Data Analysis, and Implications for Dosing and Labeling.

FDA has the legal authority to adopt a threshold of toxicological concern (TTC) for substances in food at trace levels.

PubMed

Hahn, Martin J

2010-01-01

It now is possible to detect many substances in the parts per trillion and further advances will allow for even lower levels of detection. Many of these substances may always have been present in the food supply, but escaped detection. Others may have been introduced through environmental contamination, changes in food processing, sourcing of ingredients from different manufacturers or countries, and a myriad of other reasons. The adulteration and various safety provisions of the Federal Food, Drug, and Cosmetic Act (FDCA), principles of statutory construction, and case law, provide FDA with the legal authority to adopt the threshold concept. FDA and the courts have long recognized it is possible to establish safe levels of poisonous or deleterious substances found in foods. FDA routinely conducts such an analysis under the general adulteration provisions of the FDCA and has identified safe levels for numerous environmental contaminants found in food. The courts have recognized that through its exercise of enforcement discretion, FDA has the legal authority to establish non-binding defect action levels for contaminants. FDA similarly could implement the Threshold of Toxicological Concern (TTC) through its exercise of enforcement discretion.

76 FR 23823 - Guidance for Industry on Fish and Fishery Products Hazards and Controls, Fourth Edition...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0287... AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA... analysis and critical control point (HACCP) methods. DATES: Submit either electronic or written comments on...

78 FR 20328 - Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory Committee: Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001... of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... unavailable due to unforeseen scheduling conflicts. In the meantime, FDA analysis of industry-submitted...

75 FR 13562 - Revised Draft Guidance for Industry on Pharmacokinetics in Patients With Impaired Renal Function...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... Design, Data Analysis, and Impact on Dosing and Labeling; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0133...

78 FR 3646 - Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

...The Food and Drug Administration (FDA) is proposing to amend its regulation for Current Good Manufacturing Practice In Manufacturing, Packing, or Holding Human Food (CGMPs) to modernize it and to add requirements for domestic and foreign facilities that are required to register under the Federal Food, Drug, and Cosmetic Act (the FD&C Act) to establish and implement hazard analysis and risk- based preventive controls for human food. FDA also is proposing to revise certain definitions in FDA's current regulation for Registration of Food Facilities to clarify the scope of the exemption from registration requirements provided by the FD&C Act for ``farms.'' FDA is taking this action as part of its announced initiative to revisit the CGMPs since they were last revised in 1986 and to implement new statutory provisions in the FD&C Act. The proposed rule is intended to build a food safety system for the future that makes modern, science-, and risk-based preventive controls the norm across all sectors of the food system.

Analysis of the relationship between Chalcone Isomerase gene expression level and rutin production in Ficus deltoidea var. deltoidea and F. deltoidea var. angustifolia

NASA Astrophysics Data System (ADS)

Najid, Najihah Mohd; Zain, Che Radziah Che Mohd; Zainal, Zamri

2016-11-01

Ficus deltoidea (moraceae) is a herbal plant with medicinal values. Previous studies reported that the F. deltoidea contains a high level of bioactive compounds such as flavonoids. A cDNA encodes for chalcone isomerase was identified from F. deltoidea, designated as FdCHI, which involved in the isomerization of naringenin chalcone to naringenin. Naringenin is a key branch point for the synthesis of rutin, which is believed involved in defense mechanism in the plant. Therefore, we hypothesized that there might be a direct relationship between FdCHI expression level and rutin production in leaves of F. deltoidea var. deltoidea (FDD) and F. deltoidea var. angustifolia (FDA). Our result showed that expression level of FdCHI in leaves FDD was greater than FDA. Analysis of High Performance Liquid Chromatography (HPLC) revealed that rutin was only detected in FDA leaves. Based on the results between FdCHI expression and rutin production, this study concluded that there is no relationship between FdCHI expression and rutin production in leaves of FDA and FDD.

Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies.

PubMed

Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

2017-12-05

To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%-100%) of trials in patients were registered, 71% (IQR 57%-100%) reported results or shared a CSR synopsis, 80% (70%-100%) were published and 96% (80%-100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%-100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies' transparency records and recognise exemplary companies may encourage further progress. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Current FDA regulatory guidance on the conduct of drug discrimination studies for NDA review: Does the scientific literature support recent recommendations?

PubMed

Gauvin, David V; Zimmermann, Zachary J; Kallman, Mary Jeanne

2016-11-01

The Controlled Substances Staff of the Center for Drug Evaluation and Research at the US Food and Drug Administration and the Pharmaceutical Research Manufacturers Association (PhRMA) conducted a series of open forum dialog sessions between 2006 and 2016. A Cross Company Abuse Liability Council (CCALC) was formed during the process of this unique collaborative effort between Industry and Federal Regulators whose goals were to establish the development of standards for the preclinical screening of new molecular entities for schedule control actions required as part of every New Drug Application process. The draft guidance document was published and disseminated in 2010, which allowed for alternative approaches to each study protocol requirement needed for NDA review, if the approach satisfied the requirements of the applicable statutes and regulations (i.e., the controlled substance act). In a series of recent pre-study protocol reviews requested by confidential Pharmaceutical Sponsors of MPI Research, the CSS staff appeared to change its policy and set forth to require all drug discrimination study data to be generated under "extinction" test sessions. MPI Research is a Contract Research Organization acting on behalf of pharmaceutical companies and bound under separate confidentiality agreements. The purpose of this review is to highlight the data appearing in peer-reviewed scientific journals that do not support the regulatory administrative constraints on one specific testing methodology (extinction) to the exclusion of another (reinforced test sessions). This mind shift represents a restrictive administrative policy by the FDA that is not supported by the published data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Central site monitoring: results from a test of accuracy in identifying trials and sites failing Food and Drug Administration inspection.

PubMed

Lindblad, Anne S; Manukyan, Zorayr; Purohit-Sheth, Tejashri; Gensler, Gary; Okwesili, Paul; Meeker-O'Connell, Ann; Ball, Leslie; Marler, John R

2014-04-01

Site monitoring and source document verification account for 15%-30% of clinical trial costs. An alternative is to streamline site monitoring to focus on correcting trial-specific risks identified by central data monitoring. This risk-based approach could preserve or even improve the quality of clinical trial data and human subject protection compared to site monitoring focused primarily on source document verification. To determine whether a central review by statisticians using data submitted to the Food and Drug Administration (FDA) by clinical trial sponsors can identify problem sites and trials that failed FDA site inspections. An independent Analysis Center (AC) analyzed data from four anonymous new drug applications (NDAs) where FDA had performed site inspections overseen by FDA's Office of Scientific Investigations (OSI). FDA team members in the OSI chose the four NDAs from among all NDAs with data in Study Data Tabulation Model (SDTM) format. Two of the NDAs had data that OSI had deemed unreliable in support of the application after FDA site inspections identified serious data integrity problems. The other two NDAs had clinical data that OSI deemed reliable after site inspections. At the outset, the AC knew only that the experimental design specified two NDAs with significant problems. FDA gave the AC no information about which NDAs had problems, how many sites were inspected, or how many were found to have problems until after the AC analysis was complete. The AC evaluated randomization balance, enrollment patterns, study visit scheduling, variability of reported data, and last digit reference. The AC classified sites as 'High Concern', 'Moderate Concern', 'Mild Concern', or 'No Concern'. The AC correctly identified the two NDAs with data deemed unreliable by OSI. In addition, central data analysis correctly identified 5 of 6 (83%) sites for which FDA recommended rejection of data and 13 of 15 sites (87%) for which any regulatory deviations were identified during inspection. Of the six sites for which OSI reviewed inspections and found no deviations, the central process flagged four at the lowest level of concern, one at a moderate level, and one was not flagged. Central data monitoring during the conduct of a trial while data checking was in progress was not evaluated. Systematic central monitoring of clinical trial data can identify problems at the same trials and sites identified during FDA site inspections. Central data monitoring in conjunction with an overall monitoring process that adapts to identify risks as a trial progresses has the potential to reduce the frequency of site visits while increasing data integrity and decreasing trial costs compared to processes that are dependent primarily on source documentation.

78 FR 63479 - Meta-Analyses of Randomized Controlled Clinical Trials (RCTs) for the Evaluation of Risk To...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... methodological issues that arise in the use of meta-analyses to evaluate safety risks, followed by a discussion... design, conduct and use of meta-analysis. Although many external stakeholders conduct meta-analyses, FDA... meeting. FDA expects that this meeting will build upon prior stakeholder feedback on the design, conduct...

78 FR 64735 - Current Good Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-29

...The Food and Drug Administration (FDA) is proposing regulations for domestic and foreign facilities that are required to register under the Federal Food, Drug, and Cosmetic Act (the FD&C Act) to establish requirements for current good manufacturing practice in manufacturing, processing, packing, and holding of animal food. FDA also is proposing regulations to require that certain facilities establish and implement hazard analysis and risk-based preventive controls for food for animals. FDA is taking this action to provide greater assurance that animal food is safe and will not cause illness or injury to animals or humans and is intended to build an animal food safety system for the future that makes modern, science and risk-based preventive controls the norm across all sectors of the animal food system.

Why (not) go east? Comparison of findings from FDA Investigational New Drug study site inspections performed in Central and Eastern Europe with results from the USA, Western Europe, and other parts of the world.

PubMed

Caldron, Paul H; Gavrilova, Svetlana I; Kropf, Siegfried

2012-01-01

Since the mid-1990s, investigational sites in the countries of Central and Eastern Europe (CEE) have been increasingly utilized by pharmaceutical companies because of their high productivity in terms of patient enrolment into clinical trials. Based on the FDA's publicly accessible Clinical Investigator Inspection List, we present an analysis of findings and outcome classifications from FDA inspections during Investigational New Drug (IND) studies and compare the results for the CEE region to those from Western European countries and the USA. Data from all 5531 FDA clinical trials inspections that occurred between 1994 (when the FDA first performed inspections in CEE) and the end of 2010 were entered into the database for comparative analysis. Of these, 4865 routine data audit (DA) inspections were analyzed: 401 from clinical trials performed in Western Europe, 230 in CEE, 3858 in the USA, and 376 in other countries. The average number of deficiencies per inspection ranged between 0.99 for CEE and 1.97 in Western Europe. No deficiencies were noted during 16.6%, 39.0%, and 21.5% of the inspections in Western Europe, CEE and USA, respectively. The percentages of inspections after which no follow-up action was indicated were 36.9% for Western Europe, 55.7% for CEE, and 44.3% for US sites. CEE was also the region with the lowest percentage of inspections that required official or voluntary action. On the basis of FDA inspection data, the high productivity of CEE sites appears to be accompanied by regulatory compliance as well as by data quality standards that are not inferior to those in Western regions.

Transvaginal mesh in the media following the 2011 US food and drug administration public health notification update.

PubMed

Koo, Kevin; Gormley, E Ann

2017-02-01

Prompted by patients' changing perceptions of transvaginal mesh, this study examines how mesh has been reported in the news following the 2011 US Food and Drug Administration (FDA) updated notification about the use of mesh in the treatment of pelvic organ prolapse. Two national newspaper databases were queried for articles discussing transvaginal mesh published within 3 years of the FDA announcement. Content analysis included headline subjects, mesh-related complications, quoted sources, and the FDA recommendations. To determine whether more widely read sources publish higher quality reporting, a subgroup analysis was conducted based on newspaper circulation. Ninety-five articles met inclusion criteria. Mesh-related litigation was the most common headline subject (36 articles, 38%), and 54% of all articles referenced legal action. Fifty-seven articles (60%) cited at least one mesh-related complication. Only 18 articles (19%) quoted surgeons who use transvaginal mesh. For the FDA update, 40% of articles that first reported the announcement accurately specified that it applies to mesh for prolapse, not incontinence. This ambiguity persisted: half of all articles cited the warning, but only 23% distinguished between prolapse and incontinence. Higher newspaper circulation did not significantly improve the quality of reporting about the content or context of the FDA's recommendations. Despite frequent media coverage of transvaginal mesh and its complications since 2011, very few news sources that cited the FDA warning distinguished between prolapse and incontinence. Given prevalent reporting of mesh-related litigation, the findings raise concern about how patients perceive the safety and efficacy of transvaginal mesh, regardless of indication. Neurourol. Urodynam. 36:329-332, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Comparative study of anthocyanin and volatile compounds content of four varieties of Mexican roselle (Hibiscus sabdariffa L.) by multivariable analysis.

PubMed

Camelo-Méndez, G A; Ragazzo-Sánchez, J A; Jiménez-Aparicio, A R; Vanegas-Espinoza, P E; Paredes-López, O; Del Villar-Martínez, A A

2013-09-01

Anthocyanins are a group of water-soluble pigments that provide red, purple or blue color to the leaves, flowers, and fruits. In addition, benefits have been attributed to hypertension and cardiovascular diseases. This study compared the content of total anthocyanins and volatile compounds in aqueous and ethanolic extracts of four varieties of Mexican roselle, with different levels of pigmentation. The multivariable analysis of categorical data demonstrated that ethanol was the best solvent for the extraction of both anthocyanins and volatile compounds. The concentration of anthocyanin in pigmented varieties ranged from 17.3 to 32.2 mg of cyanidin 3-glucoside/g dry weight, while volatile compounds analysis showed that geraniol was the main compound in extracts from the four varieties. The principal component analysis (PCA) allowed description of results with 77.38% of variance establishing a clear grouping for each variety in addition to similarities among some of these varieties. These results were validated by the confusion matrix obtained in the classification by the factorial discriminate analysis (FDA); it can be useful for roselle varieties classification. Small differences in anthocyanin and volatile compounds content could be detected, and it may be of interest for the food industry in order to classify a new individual into one of several groups using different variables at once.

Adjusting for publication biases across similar interventions performed well when compared with gold standard data.

PubMed

Moreno, Santiago G; Sutton, Alex J; Ades, A E; Cooper, Nicola J; Abrams, Keith R

2011-11-01

To extend, apply, and evaluate a regression-based approach to adjusting meta-analysis for publication and related biases. The approach uses related meta-analyses to improve estimation by borrowing strength on the degree of bias. The proposed adjustment approach is described. Adjustments are applied both independently and by borrowing strength across journal-extracted data on the effectiveness of 12 antidepressant drugs from placebo-controlled trials. The methods are also applied to Food and Drug Administration (FDA) data obtained on the same 12 drugs. Results are compared, viewing the FDA observed data as gold standard. Estimates adjusted for publication biases made independently for each drug were very uncertain using both the journal and FDA data. Adjusted estimates were much more precise when borrowing strength across meta-analyses. Reassuringly, adjustments in this way made to the journal data agreed closely with the observed estimates from the FDA data, while the adjusted FDA results changed only minimally from those observed from the FDA data. The method worked well in the case study considered and therefore further evaluation is encouraged. It is suggested that this approach may be especially useful when adjusting several meta-analyses on similar interventions and outcomes, particularly when there are small numbers of studies. Copyright © 2011 Elsevier Inc. All rights reserved.

Indoor tanning injuries: an evaluation of FDA adverse event reporting data.

PubMed

Dowdy, John C; Sayre, Robert M; Shepherd, James G

2009-08-01

In 1979 the Food and Drug Administration (FDA) designated indoor tanning units would be regulated medical devices and that each must have an exposure timer. In 1985 FDA added a scheduled series of doses designed to allow tanning with little risk of concomitant sunburn. Subsequently FDA/CDRH maintained databases in which medical device associated injuries were reported. The databases, MAUDE and its predecessor MDR, are available online. While these records, in part, are not intended for evaluation of adverse event rates, analysis provides insight into the etiology of UV-related tanning injuries. We compiled 142 records reported for 1985-2006 including 22% noninjury malfunctions. Of the reported injuries approximately 50% resulted from UV exposure, an average of <1/year resulted in hospitalization. At least 36% of the UV-related injuries were attributable to various (user/operator) noncompliance with FDA sunlamp guidance policies. During 1985-1995 there were six times more UV injuries than 1996-2006, presumably reflecting cessation of much mandatory reporting in 1996. Injury reports declined steady from 1997 to 2006. FDA guidance appears most efficacious in injury prevention and we encourage its incorporation into the enforceable performance standard. We also advise that tanning industry professional training programs seek standardization/accreditation of their personnel certifications through recognized accreditation bodies such as ANSI or ISO/IEC.

Advocacy for Gender Affirming Care: Learning from the Injectable Estrogen Shortage

PubMed Central

Geffen, Sophia; Horn, Tim; Smith, Kimberleigh Joy; Cahill, Sean

2018-01-01

Abstract Hormone therapy is medically necessary for many transgender individuals. The U.S. Food and Drug Administration (FDA) and pharmaceutical companies' failure to guarantee a supply of injectable estrogen in 2016 and 2017 for transgender individuals is a violation of their right to comprehensive medical treatment, free of discrimination. A series of advocacy actions eventually led to all formulations of injectable estrogen being restored to market; however, long-term solutions to supply interruptions of injectable estrogen are needed. Long-term solutions should address the lack of federally funded research and, consequently, evidence-based practice on hormone therapy for gender affirmation. PMID:29682613

Multilevel wireless capsule endoscopy video segmentation

NASA Astrophysics Data System (ADS)

Hwang, Sae; Celebi, M. Emre

2010-03-01

Wireless Capsule Endoscopy (WCE) is a relatively new technology (FDA approved in 2002) allowing doctors to view most of the small intestine. WCE transmits more than 50,000 video frames per examination and the visual inspection of the resulting video is a highly time-consuming task even for the experienced gastroenterologist. Typically, a medical clinician spends one or two hours to analyze a WCE video. To reduce the assessment time, it is critical to develop a technique to automatically discriminate digestive organs and shots each of which consists of the same or similar shots. In this paper a multi-level WCE video segmentation methodology is presented to reduce the examination time.

Analysis of lomustine drug content in FDA-approved and compounded lomustine capsules.

PubMed

KuKanich, Butch; Warner, Matt; Hahn, Kevin

2017-02-01

OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C.

PubMed

Lacy, B E; Lembo, A J; Macdougall, J E; Shiff, S J; Kurtz, C B; Currie, M G; Johnston, J M

2014-03-01

US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition. Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials. 1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively. Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies. © 2013 Ironwood Pharmaceuticals. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.

78 FR 6762 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-31

... Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for Human Food; Public Meeting... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110, 112, 114, 117, 120, 123, 129, 179, and 211 [Docket Nos. FDA-2011-N-0920 and FDA-2011-N-0921] Food and...

78 FR 10107 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-13

... Manufacturing Practice and Hazard Analysis and Risk-Based Preventive Controls for Human Food; Public Meeting... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110, 112, 114, 117, 120, 123, 129, 179, and 211 [Docket Nos. FDA-2011-N-0920 and FDA-2011-N-0921] Food and...

Changes in antidepressant medications prescribing trends in children and adolescents in Hawai'i following the FDA black box warning.

PubMed

Hassanin, Hanan; Harbi, Al; Saif, Abdullah; Davis, Jim; Easa, David; Harrigan, Rosanne

2010-01-01

To study prescribing trends for antidepressants in Hawai'i following the FDA black box warning regarding the possible risk of suicide in children and adolescents. We also explored relationships between changes in prescribing trends and patient and provider characteristics. Analysis of an existing insurance data set of prescriptions to children and adolescents within the State of Hawai'i. Children and adolescents under 18-years-old insured through the largest (>60%) third-party insurance company in the state. Our results showed variations in changes in prescribing trends for different selective serotonin reuptake inhibitors (SSRIs) following the FDA black box warning. SSRIs with more evidence-based research supporting their safety and efficacy were least affected as were those that were less implicated by the FDA analysis of the possible link between SSRIs and Suicidality. Trends were apparent for all age groups examined and for both females and males. Changes in prescribing patterns of psychiatric medications for children and adolescents in Hawai'i were identified. Differing patterns have evolved since 2003 following the series of concerns raised regarding SSRIs and suicidality in children and adolescents.

10-Year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors.

PubMed

Lowe, Gregory; Costabile, Raymond A

2012-01-01

To ensure public safety all Food and Drug Administration (FDA)-approved medications undergo postapproval safety analysis. Phosphodiesterase type-5 inhibitors (PDE5-i) are generally regarded as safe and effective. We performed a nonindustry-sponsored analysis of FDA reports for sildenafil, tadalafil, and vardenafil to evaluate the reported cardiovascular and mortality events over the past 10 years. Summarized reports of adverse events (AEs) for each PDE5-i were requested from the Center for Drug Evaluation and Research within the FDA. These data are available under the Freedom of Information Act and document industry and nonindustry reports of AEs entered into the computerized system maintained by the Office of Surveillance and Epidemiology. The data were analyzed for the number of AE reports, number of objective cardiovascular events, and reported deaths. Overall, 14,818 AEs were reported for sildenafil. There were 1,824 (12.3%) reported deaths, and reports of cardiovascular AEs numbered 2,406 (16.2%). Tadalafil was associated with 5,548 AEs and 236 deaths were reported. Vardenafil was associated with 6,085 AEs and 121 reports of deaths. The percentage of reported severe cardiovascular disorders has stabilized at 10% to 15% of all AE reports for sildenafil and tadalafil and 5% to 10% for vardenafil. Only 10% of AE reports sent to the FDA for PDE5-i were from pharmaceutical manufacturers. Reports of deaths associated with PDE5-i remain around 5% of total reported events. Despite inherent limitations from evaluating FDA reports of AEs, it is important that these reports be reviewed outside pharmaceutical industry support in order to provide due diligence and transparency. Lowe G and Costabile RA. 10-year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors. J Sex Med 2012;9:265-270. © 2011 International Society for Sexual Medicine.

Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dean, Jamie A., E-mail: jamie.dean@icr.ac.uk; Wong, Kee H.; Gay, Hiram

Purpose: Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue–sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation. Methods and Materials: FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogrammore » data. The reduced dose data were input into functional logistic regression models (functional partial least squares–logistic regression [FPLS-LR] and functional principal component–logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate–response associations, assessed using bootstrapping. Results: The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/−0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/−0.96, 0.79/−0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe toxicity in the PLR models. Dose levels greater than approximately 1.0 Gy/fraction were most strongly associated with severe acute mucositis and dysphagia in the FDA models. Conclusions: FPLS and functional principal component analysis marginally improved predictive performance compared with PLR and provided robust dose-response associations. FDA is recommended for use in normal tissue complication probability modeling.« less

Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy.

PubMed

Dean, Jamie A; Wong, Kee H; Gay, Hiram; Welsh, Liam C; Jones, Ann-Britt; Schick, Ulrike; Oh, Jung Hun; Apte, Aditya; Newbold, Kate L; Bhide, Shreerang A; Harrington, Kevin J; Deasy, Joseph O; Nutting, Christopher M; Gulliford, Sarah L

2016-11-15

Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue-sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation. FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares-logistic regression [FPLS-LR] and functional principal component-logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate-response associations, assessed using bootstrapping. The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/-0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/-0.96, 0.79/-0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe toxicity in the PLR models. Dose levels greater than approximately 1.0 Gy/fraction were most strongly associated with severe acute mucositis and dysphagia in the FDA models. FPLS and functional principal component analysis marginally improved predictive performance compared with PLR and provided robust dose-response associations. FDA is recommended for use in normal tissue complication probability modeling. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Still the Great Debate - "Fair Balance" in Direct-to-Consumer Prescription Drug Advertising Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

PubMed

Rollins, Brent L

2016-02-10

The above titled paper examined the Food and Drug Administration's (FDA's) warning letters and notice of violations (NOV) over a 10-year period. Findings from this content analysis reinforced what has been the primary issue for prescription direct-to-consumer advertising (DTCA) since its beginning, the fair balance of risk and benefit information. As opposed to another analysis in 2026 about this still being an issue, is there anything that can be done to prevent this problem from continuing? © 2016 by Kerman University of Medical Sciences.

FDA adverse Event Problem Codes: standardizing the classification of device and patient problems associated with medical device use.

PubMed

Reed, Terrie L; Kaufman-Rivi, Diana

2010-01-01

The broad array of medical devices and the potential for device failures, malfunctions, and other adverse events associated with each device creates a challenge for public health device surveillance programs. Coding reported events by type of device problem provides one method for identifying a potential signal of a larger device issue. The Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) Event Problem Codes that are used to report adverse events previously lacked a structured set of controls for code development and maintenance. Over time this led to inconsistent, ambiguous, and duplicative concepts being added to the code set on an ad-hoc basis. Recognizing the limitation of its coding system the FDA set out to update the system to improve its usefulness within FDA and as a basis of a global standard to identify important patient and device outcomes throughout the medical community. In 2004, FDA and the National Cancer Institute (NCI) signed a Memorandum of Understanding (MOU) whereby NCI agreed to provide terminology development and maintenance services to all FDA Centers. Under this MOU, CDRH's Office of Surveillance and Biometrics (OSB) convened a cross-Center workgroup and collaborated with staff at NCI Enterprise Vocabulary Service (EVS) to streamline the Patient and Device Problem Codes and integrate them into the NCI Thesaurus and Meta-Thesaurus. This initiative included many enhancements to the Event Problem Codes aimed at improving code selection as well as improving adverse event report analysis. LIMITATIONS & RECOMMENDATIONS: Staff resources, database concerns, and limited collaboration with external groups in the initial phases of the project are discussed. Adverse events associated with medical device use can be better understood when they are reported using a consistent and well-defined code set. This FDA initiative was an attempt to improve the structure and add control mechanisms to an existing code set, improve analysis tools that will better identify device safety trends, and improve the ability to prevent or mitigate effects of adverse events associated with medical device use.

We really need to talk: adapting FDA processes to rapid change.

PubMed

Lykken, Sara

2013-01-01

The rapidly evolving realm of modern commerce strains traditional regulatory paradigms. This paper traces the historical evolution of FDA crisis-response regulation and provides examples of ways in which the definitions and procedures resulting from that past continue to be challenged by new products as market entrants, some in good faith and others not, take actions that create disconnects between actual product and marketing controls and those that consumers might expect. The paper then explores some of the techniques used by other federal agencies that have faced similar challenges in environments characterized by rapid innovation, and draws from this analysis suggestions for improvement of the FDA's warning letter system.

Communicating Tobacco Product Information to the Public.

PubMed

Berman, Micah L; Byron, M Justin; Hemmerich, Natalie; Lindblom, Eric N; Lazard, Allison J; Peters, Ellen; Brewer, Noel T

2017-01-01

The 2009 Family Smoking Prevention and Tobacco Control Act (TCA) requires tobacco companies to disclose information about the harmful chemicals in their products to the U.S. Food and Drug Administration (FDA). The law requires the FDA, in turn, to communicate this information to the public "in a format that is understandable and not misleading to a lay person." But how should the FDA comply with this requirement? What does it mean for information about complex chemicals to be "understandable and not misleading to a lay person"? These questions are not easy ones to answer. Disclosures about the amount of harmful chemicals (constituents) in different tobacco products may help to inform consumers, but may also conversely prompt consumers to reach incorrect or unsupported conclusions about products' relative health risks. This paper first analyzes the FDA's legal obligation to publish tobacco constituent information so that it is "understandable and not misleading to a layperson." Second, it discusses how that legal analysis has guided scientific research examining how members of the public interpret messages regarding tobacco constituents. Lastly, this paper concludes with policy recommendations for the FDA as it considers how to comply with the law's constituent disclosure requirement while still furthering its overall objective of promoting public health.

Fluorescein diacetate for determination of cell viability in 3D fibroblast-collagen-GAG constructs.

PubMed

Powell, Heather M; Armour, Alexis D; Boyce, Steven T

2011-01-01

Quantification of cell viability and distribution within engineered tissues currently relies on representative histology, phenotypic assays, and destructive assays of viability. To evaluate uniformity of cell density throughout 3D collagen scaffolds prior to in vivo use, a nondestructive, field assessment of cell viability is advantageous. Here, we describe a field measure of cell viability in lyophilized collagen-glycosaminoglycan (C-GAG) scaffolds in vitro using fluorescein diacetate (FdA). Fibroblast-C-GAG constructs are stained 1 day after cellular inoculation using 0.04 mg/ml FdA followed by exposure to 366 nm UV light. Construct fluorescence quantified using Metamorph image analysis is correlated with inoculation density, MTT values, and histology of corresponding biopsies. Construct fluorescence correlates significantly with inoculation density (p  <  0.001) and MTT values (p  <  0.001) of biopsies collected immediately after FdA staining. No toxicity is detected in the constructs, as measured by MTT assay before and after the FdA assay at different time points; normal in vitro histology is demonstrated for the FdA-exposed constructs. In conclusion, measurement of intracellular fluorescence with FdA allows for the early, comprehensive measurement of cellular distributions and viability in engineered tissue.

Improving mental task classification by adding high frequency band information.

PubMed

Zhang, Li; He, Wei; He, Chuanhong; Wang, Ping

2010-02-01

Features extracted from delta, theta, alpha, beta and gamma bands spanning low frequency range are commonly used to classify scalp-recorded electroencephalogram (EEG) for designing brain-computer interface (BCI) and higher frequencies are often neglected as noise. In this paper, we implemented an experimental validation to demonstrate that high frequency components could provide helpful information for improving the performance of the mental task based BCI. Electromyography (EMG) and electrooculography (EOG) artifacts were removed by using blind source separation (BSS) techniques. Frequency band powers and asymmetry ratios from the high frequency band (40-100 Hz) together with those from the lower frequency bands were used to represent EEG features. Finally, Fisher discriminant analysis (FDA) combining with Mahalanobis distance were used as the classifier. In this study, four types of classifications were performed using EEG signals recorded from four subjects during five mental tasks. We obtained significantly higher classification accuracy by adding the high frequency band features compared to using the low frequency bands alone, which demonstrated that the information in high frequency components from scalp-recorded EEG is valuable for the mental task based BCI.

Disproportionality analysis of buprenorphine transdermal system and cardiac arrhythmia using FDA and WHO postmarketing reporting system data.

PubMed

Sessler, Nelson E; Walker, Ekaterina; Chickballapur, Harsha; Kacholakalayil, James; Coplan, Paul M

2017-01-01

Positive-controlled clinical studies have shown a dose dependent effect of buprenorphine transdermal system on QTc interval prolongation. This study provides assessment of the buprenorphine transdermal system and cardiac arrhythmia using US FDA and WHO postmarketing reporting databases. Disproportionality analysis of spontaneously reported adverse events to assess whether the reporting rate of cardiac arrhythmia events was disproportionately elevated relative to expected rates of reporting in both FDA and WHO databases. Cardiac arrhythmia events were identified using the standardized Medical Dictionary for Regulatory Activities query for torsade de pointes and/or QT prolongation (TdP/QTP). The threshold for a signal of disproportionate adverse event reporting was defined as the lower 90% confidence limit ≥ 2 of the Empiric Bayes geometric mean in FDA database and as the lower 95% confidence limit of the Informational Component >0 in WHO database. There were 124 (<1%) and 77 (2%) cardiac arrhythmia event cases associated with buprenorphine transdermal as compared to 3206 (12%) and 2913 (14%) involving methadone in the FDA and WHO databases, respectively. In the FDA database methadone was associated with a signal of disproportionate reporting for TdP/QTP (EB05 3.26); however, buprenorphine transdermal was not (EB05 0.33). In the WHO database methadone was associated with a signal of disproportionate reporting for TdP/QTP (IC025 2.66); however, buprenorphine transdermal was not (IC025 -0.88). Similar trends were observed in sensitivity analyses by age, gender, and specific terms related to ventricular arrhythmia. The signal identified in the transdermal buprenorphine thorough QTc study, which led to a dose limitation in its US label, does not translate into a signal of increased risk for cardiac arrhythmia in real world use, as assessed by this method of analyzing post-market surveillance data.

Fixed-dose combination and single active ingredient drugs: a comparative cost analysis.

PubMed

Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

2016-01-01

Fixed-dose combination (FDC) drugs are formulations of two or more active ingredients. To assess the pricing structure and price difference of all US FDA-approved FDCs and single drugs included in the combination. Data were collected from the FDA Orange Book and Drugs@FDA. Average Wholesale Price (AWP) unit price data were derived from The Red Book. The FDA approved 117 FDC. The average AWP difference percentage between the FDC and the sum of the single drugs in the FDC is 84.9 ± 26.2%, and varied by therapeutic class (p < 0.001). The FDC AWP averaged 83.3 ± 23.4% of the single drug AWP sum when there are no generics, and 95.1 ± 42.3% (p < 0.01) when there are two generic single active ingredients in the FDC. The price difference between FDC and single active ingredients in the combination is correlated with the therapeutic class, the year of FDC approval, and the number of single ingredients in the combination that have generics.

76 FR 20588 - FDA Food Safety Modernization Act: Focus on Preventive Controls for Facilities; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

.... FDA-2011-N-0251] FDA Food Safety Modernization Act: Focus on Preventive Controls for Facilities... comment. SUMMARY: The Food and Drug Administration (FDA) is announcing a public meeting entitled ``FDA... controls for facilities provisions of the recently enacted FDA Food Safety Modernization Act (FSMA). FDA is...

[Guidance of FDA risk evaluation and mitigation strategy and enlightenment to drug risk management of post-marketing Chinese medicine].

PubMed

Li, Yuanyuan; Xie, Yanming

2011-10-01

The FDA risk evaluation and mitigation strategy (REMS) aims to drugs or biological products known or potential serious risk management. Analysis with the example of the content of the Onsolis REMS named FOCOS. Our country can be reference for the analysis of relevant experience and establish a scientific evaluation mechanism, strengthen the drug risk consciousness, promote the rational drug use, organic combined with the before-marketing and post-marketing evaluation of traditional Chinese medicine, and promote the evaluation of risk management of the drug development and improvement.

Analysis of US Food and Drug Administration Warning Letters: False Promotional Claims Relating to Prescription and Over-the-Counter Medications.

PubMed

Salas, Maribel; Martin, Michelle; Pisu, Maria; McCall, Erin; Zuluaga, Alvaro; Glasser, Stephen P

2008-03-01

Recent studies have suggested that there has been an increase in the number of 'warning letters' issued by the US Food and Drug Administration (FDA) despite the publication of the FDA advertising guidelines. However, limited information is available on the description of warning letters. The objective of this study was to analyse the frequency and content of FDA warning letters in relation to promotional claims and discuss the influence of regulatory and industry constraints on promotion. All warning letters published by the FDA between 5 May 1995 and 11 June 2007 were reviewed. Warning letters related to promotional issues were included and analysed. Information related to the identification number, date of the warning letter, FDA division that issued the letter, drug name, manufacturer, specific warning problem, type of promotional material and requested action was extracted. Two independent investigators reviewed and classified each PDF file, any differences were discussed until a consensus was reached. Between May 1995 and June 2007 a total of 8692 warning letters were issued, of which 25% were related to drugs. Of these, 206 warning letters focused on drug promotion and were included in this study: 23% were issued in 2005, 15% in 2004 and 14% in 1998. In total, 47% of the warning letters were issued because of false or misleading unapproved doses and uses, 27% failed to disclose risks, 15% cited misleading promotion, 8% related to misleading labelling and 3% promoted false effectiveness claims. There is an important variation in the number of warning letters issued in the last decade, probably because of the increasing number of drugs approved by the FDA, drug withdrawal scandals, and the publication of the FDA and the Pharmaceutical Research and Manufacturers of America (PhRMA) guidelines. We found that benefit-related claims, such as unapproved uses or doses of drugs, and failure to disclose risks, are the main causes of FDA issued warning letters for promotional claims related to medications.

Impact of the FDA warning of potential ceftriaxone and calcium interactions on drug use policy in clinical practice.

PubMed

Esterly, John S; Steadman, Emily; Scheetz, Marc H

2011-06-01

In September 2007, the FDA issued an alert recommending that ceftriaxone and calcium-containing solutions should not be administered to any patient within 48 h of each other. Due to the widespread use of ceftriaxone, significant concern was expressed by the greater healthcare community about the warning, which the FDA eventually retracted in April of 2009. We sought to quantify the impact of the warning on healthcare institutions. A survey was administered to the membership of the Society of Infectious Diseases Pharmacists to quantify perceived changes in ceftriaxone use among healthcare institutions across the United States. A survey of Infectious Diseases experts was conducted. Participants were queried for hospital policies/drug use statistics during two times: immediately after the FDA warning and approximately 13 months post warning (preceding the FDA retraction). Related changes in formulary, drug-use policy, and the number of employee hours that were devoted to addressing the FDA warning were assessed. Ninety-four surveys representing 94 hospital systems were included in the analysis. Approximately half (n = 49, 52%) of respondent institutions enacted at least one drug-use policy change based on the warning; one institution removed ceftriaxone from a clinical protocol. Institutions' final interpretations of the warning differed slightly from initial understanding of the warning, and there was an overall minor decrease in the perceived use of ceftriaxone. The majority of those surveyed (n = 70, 74%) estimated that their respective institutions devoted between 1 and 49 employee hours to address the warning. Hospitals with ID pharmacists had minimal changes to ceftriaxone use after the 2007 FDA warning. Specialized pharmacists may be uniquely situated to help hospitals interpret global recommendations locally.

Drugs@FDA: FDA Approved Drug Products

MedlinePlus

... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

Changes in FDA enforcement activities following changes in federal administration: the case of regulatory letters released to pharmaceutical companies.

PubMed

Nguyen, Diane; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Montagne, Michael

2013-01-22

The United States (US) Food and Drug Administration (FDA) is responsible for the protection of the public health by assuring the safety, effectiveness and security of human drugs and biological products through the enforcement of the Federal Food, Drug and Cosmetic Act (FDCA) and related regulations. These enforcement activities include regulatory letters (i.e. warning letters and notice of violation) to pharmaceutical companies. A regulatory letter represents the FDA's first official notification to a pharmaceutical company that the FDA has discovered a product or activity in violation of the FDCA.This study analyzed trends in the pharmaceutical-related regulatory letters released by the FDA during the period 1997-2011 and assessed differences in the average number and type of regulatory letters released during the last four federal administrations. Data derived from the FDA webpage. Information about the FDA office releasing the letter, date, company, and drug-related violation was collected. Regulatory letters were classified by federal administration. Descriptive statistics were performed for the analysis. Between 1997 and 2011 the FDA released 2,467 regulatory letters related to pharmaceuticals. FDA headquarters offices released 50.6% and district offices 49.4% of the regulatory letters. The Office of Prescription Drug Promotion released the largest number of regulatory letters (850; 34.5% of the total), followed by the Office of Scientific Investigations (131; 5.3%), and the Office of Compliance (105; 4.3%). During the 2nd Clinton Administration (1997-2000) the average number of regulatory letters per year was 242.8 ± 45.6, during the Bush Administration (2001-2008) it was 120.4 ± 33.7, and during the first three years of the Obama administration (2009-2011) it was 177.7.0 ± 17.0. The average number of regulatory letters released by the Office of Prescription Drug Promotion also varied by administration: Clinton (122.3 ± 36.4), Bush (29.5 ± 16.2) and Obama (41.7 ± 11.1). Most regulatory letters released by FDA headquarters were related to marketing and advertising activities of pharmaceutical companies. The number of regulatory letters was highest during the second Clinton administration, diminished during the Bush administrations, and increased again during the Obama administration. A further assessment of the impact of changes in federal administration on the enforcement activities of the FDA is required.

Analysis of the discriminative inhibition of mammalian digestive lipases by 3-phenyl substituted 1,3,4-oxadiazol-2(3H)-ones.

PubMed

Point, Vanessa; Pavan Kumar, K V P; Marc, Sylvain; Delorme, Vincent; Parsiegla, Goetz; Amara, Sawsan; Carrière, Frédéric; Buono, Gérard; Fotiadu, Frédéric; Canaan, Stéphane; Leclaire, Julien; Cavalier, Jean-François

2012-12-01

We report here the reactivity and selectivity of three 5-Methoxy-N-3-Phenyl substituted-1,3,4-Oxadiazol-2(3H)-ones (MPOX, as well as meta and para-PhenoxyPhenyl derivatives, i.e.MmPPOX and MpPPOX) with respect to the inhibition of mammalian digestive lipases: dog gastric lipase (DGL), human (HPL) and porcine (PPL) pancreatic lipases, human (HPLRP2) and guinea pig (GPLRP2) pancreatic lipase-related proteins 2, human pancreatic carboxyl ester hydrolase (hCEH), and porcine pancreatic extracts (PPE). All three oxadiazolones displayed similar inhibitory activities on DGL, PLRP2s and hCEH than the FDA-approved anti-obesity drug Orlistat towards the same enzymes. These compounds appeared however to be discriminative of HPL (poorly inhibited) and PPL (fully inhibited). The inhibitory activities obtained experimentally in vitro were further rationalized using in silico molecular docking. In the case of DGL, we demonstrated that the phenoxy group plays a key role in specific molecular interactions within the lipase's active site. The absence of this group in the case of MPOX, as well as its connectivity to the neighbouring aromatic ring in the case of MmPPOX and MpPPOX, strongly impacts the inhibitory efficiency of these oxadiazolones and leads to a significant gain in selectivity towards the lipases tested. The powerful inhibition of PPL, DGL, PLRP2s, hCEH and to a lesser extend HPL, suggests that oxadiazolone derivatives could also provide useful leads for the development of novel and more discriminative inhibitors of digestive lipases. These inhibitors could be used for a better understanding of individual lipase function as well as for drug development aiming at the regulation of the whole gastrointestinal lipolysis process. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

The rise (and decline?) of biotechnology.

PubMed

Kinch, Michael S

2014-11-01

Since the 1970s, biotechnology has been a key innovator in drug development. An analysis of FDA-approved therapeutics demonstrates pharmaceutical companies outpace biotechs in terms of new approvals but biotechnology companies are now responsible for earlier-stage activities (patents, INDs or clinical development). The number of biotechnology organizations that contributed to an FDA approval began declining in the 2000s and is at a level not seen since the 1980s. Whereas early biotechnology companies had a decade from first approval until acquisition, the average acquisition of a biotechnology company now occurs months before their first FDA approval. The number of hybrid organizations that arise when pharmaceutical companies acquire biotechnology is likewise declining, raising questions about the sustainability of biotechnology. Copyright © 2014 Elsevier Ltd. All rights reserved.

2-Furaldehyde diethyl acetal from tender coconut water (Cocos nucifera) attenuates biofilm formation and quorum sensing-mediated virulence of Chromobacterium violaceum and Pseudomonas aeruginosa.

PubMed

Sethupathy, Sivasamy; Nithya, Chari; Pandian, Shunmugiah Karutha

2015-01-01

The aim of this study was to evaluate the anti-biofilm and quorum sensing inhibitory (QSI) potential of tender coconut water (TCW) against Chromobacterium violaceum and Pseudomonas aeruginosa. TCW significantly inhibited the QS regulated violacein, virulence factors and biofilm production without affecting their growth. qRT-PCR analysis revealed the down-regulation of autoinducer synthase, transcriptional regulator and virulence genes. Mass-spectrometric analysis of a petroleum ether extract of the TCW hydrolyte revealed that 2-furaldehyde diethyl acetal (2FDA) and palmitic acid (PA) are the major compounds. In vitro bioassays confirmed the ability of 2FDA to inhibit the biofilm formation and virulence factors. In addition, the combination of PA with 2FDA resulted in potent inhibition of biofilm formation and virulence factors. The results obtained strongly suggest that TCW can be exploited as a base for designing a novel antipathogenic drug formulation to treat biofilm mediated infections caused by P. aeruginosa.

Iodine in food- and dietary supplement–composition databases123

PubMed Central

Pehrsson, Pamela R; Patterson, Kristine Y; Spungen, Judith H; Wirtz, Mark S; Andrews, Karen W; Dwyer, Johanna T; Swanson, Christine A

2016-01-01

The US Food and Drug Administration (FDA) and the Nutrient Data Laboratory (NDL) of the USDA Agricultural Research Service have worked independently on determining the iodine content of foods and dietary supplements and are now harmonizing their efforts. The objective of the current article is to describe the harmonization plan and the results of initial iodine analyses accomplished under that plan. For many years, the FDA’s Total Diet Study (TDS) has measured iodine concentrations in selected foods collected in 4 regions of the country each year. For more than a decade, the NDL has collected and analyzed foods as part of the National Food and Nutrient Analysis Program; iodine analysis is now being added to the program. The NDL recently qualified a commercial laboratory to conduct iodine analysis of foods by an inductively coupled plasma mass spectrometry (ICP-MS) method. Co-analysis of a set of samples by the commercial laboratory using the ICP-MS method and by the FDA laboratory using its standard colorimetric method yielded comparable results. The FDA recently reviewed historical TDS data for trends in the iodine content of selected foods, and the NDL analyzed samples of a limited subset of those foods for iodine. The FDA and the NDL are working to combine their data on iodine in foods and to produce an online database that can be used for estimating iodine intake from foods in the US population. In addition, the NDL continues to analyze dietary supplements for iodine and, in collaboration with the NIH Office of Dietary Supplements, to publish the data online in the Dietary Supplement Ingredient Database. The goal is to provide, through these 2 harmonized databases and the continuing TDS focus on iodine, improved tools for estimating iodine intake in population studies. PMID:27534627

Laboratory-based testing to evaluate abuse-deterrent formulations and satisfy the Food and Drug Administration's recommendation for Category 1 Testing.

PubMed

Altomare, Christopher; Kinzler, Eric R; Buchhalter, August R; Cone, Edward J; Costantino, Anthony

The US Food and Drug Administration (FDA) considers the development of abuse-deterrent formulations of solid oral dosage forms a public health priority and has outlined a series of premarket studies that should be performed prior to submitting an application to the Agency. Category 1 studies are performed to characterize whether the abuse-deterrent properties of a new formulation can be easily defeated. Study protocols are designed to evaluate common abuse patterns of prescription medications as well as more advanced methods that have been reported on drug abuse websites and forums. Because FDA believes Category 1 testing should fully characterize the abuse-deterrent characteristics of an investigational formulation, Category 1 testing is time consuming and requires specialized laboratory resources as well as advanced knowledge of prescription medication abuse. Recent Advisory Committee meetings at FDA have shown that Category 1 tests play a critical role in FDA's evaluation of an investigational formulation. In this article, we will provide a general overview of the methods of manipulation and routes of administration commonly utilized by prescription drug abusers, how those methods and routes are evaluated in a laboratory setting, and discuss data intake, analysis, and reporting to satisfy FDA's Category 1 testing requirements.

Menthol smokers: metabolomic profiling and smoking behavior

PubMed Central

Hsu, Ping-Ching; Lan, Renny S.; Brasky, Theodore M.; Marian, Catalin; Cheema, Amrita K.; Ressom, Habtom W.; Loffredo, Christopher A.; Pickworth, Wallace B.; Shields, Peter G.

2016-01-01

Background The use of menthol in cigarettes and marketing is under consideration for regulation by the FDA. However, the effects of menthol on smoking behavior and carcinogen exposure have been inconclusive. We previously reported metabolomic profiling for cigarette smokers, and novelly identified a menthol-glucuronide (MG) as the most significant metabolite directly related to smoking. Here, MG is studied in relation to smoking behavior and metabolomic profiles. Methods A cross-sectional study of 105 smokers who smoked two cigarettes in the laboratory one hour apart. Blood nicotine, MG and exhaled carbon monoxide (CO) boosts were determined (the difference before and after smoking). Spearman's correlation, Chi-Square and ANCOVA adjusted for gender, race and cotinine levels for menthol smokers assessed the relationship of MG boost, smoking behavior, and metabolic profiles. Multivariate metabolite characterization using supervised Partial Least Squares-Discriminant Analysis (PLS-DA) was carried out for the classification of metabolomics profiles. Results MG boost was positively correlated with CO boost, nicotine boost, average puff volume, puff duration, and total smoke exposure. Classification using PLS-DA, MG was the top metabolite discriminating metabolome of menthol vs. non-menthol smokers. Among menthol smokers, forty-two metabolites were significantly correlated with MG boost, which linked to cellular functions such as of cell death, survival, and movement. Conclusion Plasma MG boost is a new smoking behavior biomarker that may provides novel information over self-reported use of menthol cigarettes by integrating different smoking measures for understanding smoking behavior and harm of menthol cigarettes. Impacts These results provide insight into the biological effect of menthol smoking. PMID:27628308

Why (not) go east? Comparison of findings from FDA Investigational New Drug study site inspections performed in Central and Eastern Europe with results from the USA, Western Europe, and other parts of the world

PubMed Central

Caldron, Paul H; Gavrilova, Svetlana I; Kropf, Siegfried

2012-01-01

Since the mid-1990s, investigational sites in the countries of Central and Eastern Europe (CEE) have been increasingly utilized by pharmaceutical companies because of their high productivity in terms of patient enrolment into clinical trials. Based on the FDA’s publicly accessible Clinical Investigator Inspection List, we present an analysis of findings and outcome classifications from FDA inspections during Investigational New Drug (IND) studies and compare the results for the CEE region to those from Western European countries and the USA. Data from all 5531 FDA clinical trials inspections that occurred between 1994 (when the FDA first performed inspections in CEE) and the end of 2010 were entered into the database for comparative analysis. Of these, 4865 routine data audit (DA) inspections were analyzed: 401 from clinical trials performed in Western Europe, 230 in CEE, 3858 in the USA, and 376 in other countries. The average number of deficiencies per inspection ranged between 0.99 for CEE and 1.97 in Western Europe. No deficiencies were noted during 16.6%, 39.0%, and 21.5% of the inspections in Western Europe, CEE and USA, respectively. The percentages of inspections after which no follow-up action was indicated were 36.9% for Western Europe, 55.7% for CEE, and 44.3% for US sites. CEE was also the region with the lowest percentage of inspections that required official or voluntary action. On the basis of FDA inspection data, the high productivity of CEE sites appears to be accompanied by regulatory compliance as well as by data quality standards that are not inferior to those in Western regions. PMID:22563236

The Drug Safety and Risk Management Advisory Committee: a case study of meeting frequency, content, and outcomes before and after FDAAA.

PubMed

Morrato, Elaine H; Ling, Sarah B

2012-11-01

The Food and Drug Administration Amendments Act (FDAAA) of 2007 granted FDA-expanded drug safety authority. We hypothesized that meetings involving the FDA Drug Safety and Risk Management (DSaRM) Advisory Committee might serve as a barometer for the impact of FDAAA on drug safety regulatory decision making. We conducted a case study analysis of 42 DSaRM advisory committee meetings held between 2002 and 2011. Publicly available sources (FDA meeting minutes and materials, safety alerts, and drug manufacturer Web sites) were reviewed to describe and compare DSaRM meeting frequency, content and outcomes between the pre-FDAAA (2002-2007) and post-FDAAA (2008-2011) periods. DSaRM meeting frequency increased after FDAAA (from 2.7 to 6.5 meetings per year). DSaRM meetings were more likely to be held jointly with other drug advisory committees after FDAAA (from 68% to 92% of meetings). DSaRM members were invited participants in 35 additional meetings of other drug advisory committees (2007-2011). DSaRM meetings were more likely to review issues of approvability (eg, new drugs, new indications, and new product formulations) after FDAAA. FDA questions to the committee were more likely to request an explicit drug safety assessment after FDAAA (from 31% to 76% of meetings). Content analysis of meeting outcomes and subsequent FDA regulatory decisions did not suggest a more or less risk aversive climate after FDAAA. Increased DSaRM advisory committee activity indicates its advice was being sought more broadly for drug regulatory decision making and at earlier stages of drug development after FDAAA was enacted.

FDA Escherichia coli Identification (FDA-ECID) Microarray: a Pangenome Molecular Toolbox for Serotyping, Virulence Profiling, Molecular Epidemiology, and Phylogeny

PubMed Central

Patel, Isha R.; Gangiredla, Jayanthi; Lacher, David W.; Mammel, Mark K.; Jackson, Scott A.; Lampel, Keith A.

2016-01-01

ABSTRACT Most Escherichia coli strains are nonpathogenic. However, for clinical diagnosis and food safety analysis, current identification methods for pathogenic E. coli either are time-consuming and/or provide limited information. Here, we utilized a custom DNA microarray with informative genetic features extracted from 368 sequence sets for rapid and high-throughput pathogen identification. The FDA Escherichia coli Identification (FDA-ECID) platform contains three sets of molecularly informative features that together stratify strain identification and relatedness. First, 53 known flagellin alleles, 103 alleles of wzx and wzy, and 5 alleles of wzm provide molecular serotyping utility. Second, 41,932 probe sets representing the pan-genome of E. coli provide strain-level gene content information. Third, approximately 125,000 single nucleotide polymorphisms (SNPs) of available whole-genome sequences (WGS) were distilled to 9,984 SNPs capable of recapitulating the E. coli phylogeny. We analyzed 103 diverse E. coli strains with available WGS data, including those associated with past foodborne illnesses, to determine robustness and accuracy. The array was able to accurately identify the molecular O and H serotypes, potentially correcting serological failures and providing better resolution for H-nontypeable/nonmotile phenotypes. In addition, molecular risk assessment was possible with key virulence marker identifications. Epidemiologically, each strain had a unique comparative genomic fingerprint that was extended to an additional 507 food and clinical isolates. Finally, a 99.7% phylogenetic concordance was established between microarray analysis and WGS using SNP-level data for advanced genome typing. Our study demonstrates FDA-ECID as a powerful tool for epidemiology and molecular risk assessment with the capacity to profile the global landscape and diversity of E. coli. IMPORTANCE This study describes a robust, state-of-the-art platform developed from available whole-genome sequences of E. coli and Shigella spp. by distilling useful signatures for epidemiology and molecular risk assessment into one assay. The FDA-ECID microarray contains features that enable comprehensive molecular serotyping and virulence profiling along with genome-scale genotyping and SNP analysis. Hence, it is a molecular toolbox that stratifies strain identification and pathogenic potential in the contexts of epidemiology and phylogeny. We applied this tool to strains from food, environmental, and clinical sources, resulting in significantly greater phylogenetic and strain-specific resolution than previously reported for available typing methods. PMID:27037122

Participation of Women and Sex Analyses in Late-Phase Clinical Trials of New Molecular Entity Drugs and Biologics Approved by the FDA in 2007–2009

PubMed Central

Poon, Rita; Khanijow, Keshav; Umarjee, Sphoorti; Yu, Monica; Zhang, Lei; Parekh, Ameeta

2013-01-01

Abstract Background Biological sex differences may contribute to differential treatment outcomes for therapeutic products. This study tracks women's participation in late-phase clinical trials (LPCTs), where efficacy and safety of drugs and biologics are evaluated, of new molecular entity (NME) drugs and biologics approved by the U.S. Food and Drug Administration (FDA) in 2007–2009. Furthermore, presentations of sex-based analyses were assessed from the FDA reviews. Methods New drug applications (NDAs) and biologics license applications (BLAs) were accessed from the U.S. FDA database and evaluated for women's participation in LPCTs. Sex-based analyses for efficacy and safety contained in FDA reviews were surveyed. Ratios for women's LPCT participation (PROPORTION OF STUDY SUBJECTS) to their proportion in the disease population were calculated for each approved therapeutic product and grouped into therapeutic categories. Results Sex-specific (n=5) and pediatric (n=3) drug applications were excluded. Women's participation in LPCTs was 39%, 48%, and 42% in NDAs (n=50) and 49%, 62%, and 58% in BLAs (n=11) for 2007, 2008, and 2009, respectively. Sixty-four percent of NDAs and 91% of BLAs had participation to proportion ratios of ≥0.80. Seventy-four percent of NDA reviews and 64% of BLA reviews included safety and efficacy sex analysis. Ninety-six percent of NDA reviews and 100% of BLA reviews included efficacy sex analysis. Conclusion Women's participation in LPCTs averaged 43% for NDAs and 57% for BLAs in 2007–2009 and varied widely by indication. As a comparison, the 2001 U.S. Government Accountability Office (GAO) reported 52% of women's participation for drug clinical trials in1998–2000 and an FDA study reported 45% for BLAs approved from 1995 to 1999. This study showed that sex-analysis of both safety and efficacy in NDA has increased to 74% since the GAO report of 72%, while those for BLAs increased to 64% from 37% reported for therapeutic biologics approved in 1995–1999. Knowledge of disease prevalence and participation in clinical trials provides an understanding of recruitment and retention patterns of patients in these trials. PMID:23768021

78 FR 19715 - Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1153] Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish Pilot Projects and...: The Food and Drug Administration (FDA) is extending the comment period for the notice entitled...

Statistical innovations in the medical device world sparked by the FDA.

PubMed

Campbell, Gregory; Yue, Lilly Q

2016-01-01

The world of medical devices while highly diverse is extremely innovative, and this facilitates the adoption of innovative statistical techniques. Statisticians in the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration (FDA) have provided leadership in implementing statistical innovations. The innovations discussed include: the incorporation of Bayesian methods in clinical trials, adaptive designs, the use and development of propensity score methodology in the design and analysis of non-randomized observational studies, the use of tipping-point analysis for missing data, techniques for diagnostic test evaluation, bridging studies for companion diagnostic tests, quantitative benefit-risk decisions, and patient preference studies.

Differences in reproductive toxicology between alopecia drugs: an analysis on adverse events among female and male cases

PubMed Central

Li, Qingfeng

2016-01-01

Alopecia is a dermatological condition with limited therapeutic options. Only two drugs, finasteride and minoxidil, are approved by FDA for alopecia treatment. However, little is known about the differences in adverse effects between these two drugs. We examined the clinical reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2004 to 2014. For both female and males, finasteride was found to be more associated with reproductive toxicity as compared to minoxidil. Among male alopecia cases, finasteride was significantly more concurrent with several forms of sexual dysfunction. Among female alopecia cases, finasteride was significantly more concurrent with harm to fetus and disorder of uterus. In addition, drug-gene network analysis indicated that finasteride could profoundly disturb pathways related to sex hormone signaling and oocyte maturation. These findings could provide clues for subsequent toxicological research. Taken together, this analysis suggested that finasteride could be more liable to various reproductive adverse effects. Some of these adverse effects have yet to be warned in FDA-approved drug label. This information can help improve the treatment regimen of alopecia and post-marketing regulation of drug products. PMID:27738338

Considering the Future of Pharmaceutical Promotions in Social Media

PubMed Central

Carpentier, Francesca Renee Dillman

2016-01-01

This commentary explores the implications of increased social media marketing by drug manufacturers, based on findings in Hyosun Kim’s article of the major themes in recent Food and Drug Administration (FDA) warning letters and notices of violation regarding online direct-to-consumer promotions of pharmaceuticals. Kim’s rigorous analysis of FDA letters over a 10-year span highlights a relative abundance of regulatory action toward marketer-controlled websites and sponsored advertisements, compared to branded and unbranded social media messaging. However, social media marketing efforts are increasing, as is FDA attention to these efforts. This commentary explores recent developments and continuing challenges in the FDA’s attempts to provide guidance and define pharmaceutical company accountability in marketer-controlled and -uncontrolled claims disseminated through social media. PMID:27239874

77 FR 14404 - Guidance for the Public, Food and Drug Administration (FDA) Advisory Committee Members, and FDA...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2002-D-0094; (formerly Docket No. 02D-0049)] Guidance for the Public, Food and Drug Administration (FDA) Advisory... Food and Drug Administration (FDA) is announcing the availability of a guidance for the public, FDA...

78 FR 950 - Medical Devices; Availability of Safety and Effectiveness Summaries for Premarket Approval...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-07

..., FDA- 2012-M-0965, FDA-2012-M-0968, FDA-2012-M-1011, and FDA-2012-M-1013] Medical Devices; Availability...\\ February 16, 2011. Adjustable Gastric Banding System. P100049, FDA-2012-M-0893....... Torax Medical, Inc.... Trabecular Micro- Bypass Stent and Inserter. P110007, FDA-2012-M-0734....... Abbott Medical Healon[supreg...

75 FR 76992 - Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: The Open Public Hearing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-10

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2005-D-0072] (formerly Docket No. 2005D-0042) Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: The Open Public Hearing at FDA Advisory Committee Meetings; Availability AGENCY: Food and Drug...

78 FR 14309 - Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1153] Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish Pilot Projects and... information. SUMMARY: In September 2011, the Food and Drug Administration (FDA or the Agency) asked the...

Detection of colorectal cancer (CRC) by urinary volatile organic compound analysis.

PubMed

Arasaradnam, Ramesh P; McFarlane, Michael J; Ryan-Fisher, Courtenay; Westenbrink, Erik; Hodges, Phoebe; Hodges, Paula; Thomas, Matthew G; Chambers, Samantha; O'Connell, Nicola; Bailey, Catherine; Harmston, Christopher; Nwokolo, Chuka U; Bardhan, Karna D; Covington, James A

2014-01-01

Colorectal cancer (CRC) is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB) testing has largely been superseded by Faecal Immunochemical testing (FIT), but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs) signature(s) for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer). FAIMS is able to identify Inflammatory Bowel disease (IBD) patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK). Data was processed using Fisher Discriminant Analysis (FDA) after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS) with potential as a novel screening tool.

Clinical Evidence Supporting US Food and Drug Administration Premarket Approval of High-Risk Otolaryngologic Devices, 2000-2014.

PubMed

Rathi, Vinay K; Wang, Bo; Ross, Joseph S; Downing, Nicholas S; Kesselheim, Aaron S; Gray, Stacey T

2017-02-01

The US Food and Drug Administration (FDA) approves high-risk medical devices based on premarket pivotal clinical studies demonstrating reasonable assurance of safety and effectiveness and may require postapproval studies (PAS) to further inform benefit-risk assessment. We conducted a cross-sectional analysis using publicly available FDA documents to characterize industry-sponsored pivotal studies and PAS of high-risk devices used in the treatment of otolaryngologic diseases. Between 2000 and 2014, the FDA approved 23 high-risk otolaryngologic devices based on 28 pivotal studies. Median enrollment was 118 patients (interquartile range, 67-181), and median duration of longest primary effectiveness end point follow-up was 26 weeks (interquartile range, 16-96). Fewer than half were randomized (n = 13, 46%), blinded (n = 12, 43%), or controlled (n = 10, 36%). The FDA required 23 PASs for 16 devices (70%): almost two-thirds (n = 15, 65%) monitored long-term performance, and roughly one-third (n = 8, 35%) focused on subgroups. Otolaryngologists should be aware of limitations in the strength of premarket evidence when considering the use of newly approved devices.

Perceptions of the Food and Drug Administration as a Tobacco Regulator

PubMed Central

Jarman, Kristen L.; Ranney, Leah M.; Baker, Hannah M.; Vallejos, Quirina M.; Goldstein, Adam O.

2017-01-01

Objectives The U. S. Food and Drug Administration (FDA) now has regulatory authority over all tobacco products. Little is known about public awareness and perceptions of FDA in their new role as a tobacco regulator. This research utilizes focus groups to examine perceptions of FDA as a tobacco regulator so that FDA can better communicate with the public about this role. Methods We conducted 6 focus groups in 2014 among a diverse sample of smokers and non-smokers. Participants were asked if they had heard of FDA, what they knew about FDA, if they associated FDA with tobacco, and their thoughts about this FDA role. Results A total of 41 individuals participated. Although nearly all participants had heard of FDA, most were not aware of FDA’s regulatory authority over tobacco products, did not associate the role of FDA with tobacco, and some drew comparisons between FDA’s work in tobacco and their work regulating food and drugs. Conclusion Data suggest that although public awareness of FDA regulatory authority over tobacco is low, with proper public education, the public may find FDA to be a trustworthy source of tobacco regulation. PMID:29051917

Research misconduct identified by the US Food and Drug Administration: out of sight, out of mind, out of the peer-reviewed literature.

PubMed

Seife, Charles

2015-04-01

Every year, the US Food and Drug Administration (FDA) inspects several hundred clinical sites performing biomedical research on human participants and occasionally finds evidence of substantial departures from good clinical practice and research misconduct. However, the FDA has no systematic method of communicating these findings to the scientific community, leaving open the possibility that research misconduct detected by a government agency goes unremarked in the peer-reviewed literature. To identify published clinical trials in which an FDA inspection found significant evidence of objectionable conditions or practices, to describe violations, and to determine whether the violations are mentioned in the peer-reviewed literature. Cross-sectional analysis of publicly available documents, dated from January 1, 1998, to September 30, 2013, describing FDA inspections of clinical trial sites in which significant evidence of objectionable conditions or practices was found. For each inspection document that could be linked to a specific published clinical trial, the main measure was a yes/no determination of whether there was mention in the peer-reviewed literature of problems the FDA had identified. Fifty-seven published clinical trials were identified for which an FDA inspection of a trial site had found significant evidence of 1 or more of the following problems: falsification or submission of false information, 22 trials (39%); problems with adverse events reporting, 14 trials (25%); protocol violations, 42 trials (74%); inadequate or inaccurate recordkeeping, 35 trials (61%); failure to protect the safety of patients and/or issues with oversight or informed consent, 30 trials (53%); and violations not otherwise categorized, 20 trials (35%). Only 3 of the 78 publications (4%) that resulted from trials in which the FDA found significant violations mentioned the objectionable conditions or practices found during the inspection. No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published. When the FDA finds significant departures from good clinical practice, those findings are seldom reflected in the peer-reviewed literature, even when there is evidence of data fabrication or other forms of research misconduct.

Impacts analysis regarding partially hydrogenated oils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Ellen D.; Turhollow, Jr., Anthony F.; Zimmerman, Gregory P..

The U.S. Food and Drug Administration (FDA) has the responsibility under the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 United States Code (U.S.C.) 301 et seq.] for assuring that the U.S. food supply is safe, sanitary, wholesome, and honestly labeled. Toward that end, FDA exercised approval authority over substances permitted for use as food additives. Substances that are generally recognized as safe (GRAS) are not subject to regulation as food additives under the FD&C Act.

Neodymium: YAG lasers. An FDA report.

PubMed

Stark, W J; Worthen, D; Holladay, J T; Murray, G

1985-02-01

Analysis of data from four neodymium:YAG laser manufacturers submitted to the Food and Drug Administration (FDA) on over 17,000 cases indicate the procedure is safe and effective for cutting opaque posterior lens capsules. A successful opening in the pupillary membrane was achieved in 98% of the cases, and vision improved in 84% of the cases. Clinically significant risks include: a rise in intraocular pressure two to four hours after treatment, damage to the intraocular lens, and rupture of the anterior hyaloid face.

Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012

PubMed Central

Miller, Jennifer E; Korn, David; Ross, Joseph S

2015-01-01

Objective To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. Design Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. Data sources Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications. Main outcome measures Clinical trial registration and results reporting in ClinicalTrials.gov, publication in the medical literature, and compliance with the 2007 FDA Amendments Acts (FDAAA), analysed on the drug level. Results The FDA approved 15 drugs sponsored by 10 large companies in 2012. We identified 318 relevant trials involving 99 599 research participants. Per drug, a median of 57% (IQR 32–83%) of trials were registered, 20% (IQR 12–28%) reported results in ClinicalTrials.gov, 56% (IQR 41–83%) were published, and 65% (IQR 41–83%) were either published or reported results. Almost half of all reviewed drugs had at least one undisclosed phase II or III trial. Per drug, a median of 17% (IQR 8–20%) of trials supporting FDA approvals were subject to FDAAA mandated public disclosure; of these, a median of 67% (IQR 0–100%) were FDAAA-compliant. 68% of research participants (67 629 of 99 599) participated in FDAAA-subject trials, with 51% (33 405 of 67 629) enrolled in non-compliant trials. Transparency varied widely among companies. Conclusions Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve compliance with legal and ethics standards and the quality of medical knowledge. PMID:26563214

Toward evidence-based medical statistics: a Bayesian analysis of double-blind placebo-controlled antidepressant trials in the treatment of anxiety disorders.

PubMed

Monden, Rei; de Vos, Stijn; Morey, Richard; Wagenmakers, Eric-Jan; de Jonge, Peter; Roest, Annelieke M

2016-12-01

The Food and Drug Administration (FDA) uses a p < 0.05 null-hypothesis significance testing framework to evaluate "substantial evidence" for drug efficacy. This framework only allows dichotomous conclusions and does not quantify the strength of evidence supporting efficacy. The efficacy of FDA-approved antidepressants for the treatment of anxiety disorders was re-evaluated in a Bayesian framework that quantifies the strength of the evidence. Data from 58 double-blind placebo-controlled trials were retrieved from the FDA for the second-generation antidepressants for the treatment of anxiety disorders. Bayes factors (BFs) were calculated for all treatment arms compared to placebo and were compared with the corresponding p-values and the FDA conclusion categories. BFs ranged from 0.07 to 131,400, indicating a range of no support of evidence to strong evidence for the efficacy. Results also indicate a varying strength of evidence between the trials with p < 0.05. In sum, there were large differences in BFs across trials. Among trials providing "substantial evidence" according to the FDA, only 27 out of 59 dose groups obtained strong support for efficacy according to the typically used cutoff of BF ≥ 20. The Bayesian framework can provide valuable information on the strength of the evidence for drug efficacy. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Network Analysis of Drug-target Interactions: A Study on FDA-approved New Molecular Entities Between 2000 to 2015.

PubMed

Lin, Hui-Heng; Zhang, Le-Le; Yan, Ru; Lu, Jin-Jian; Hu, Yuanjia

2017-09-25

The U.S. Food and Drug Administration (FDA) approves new drugs every year. Drug targets are some of the most important interactive molecules for drugs, as they have a significant impact on the therapeutic effects of drugs. In this work, we thoroughly analyzed the data of small molecule drugs approved by the U.S. FDA between 2000 and 2015. Specifically, we focused on seven classes of new molecular entity (NME) classified by the anatomic therapeutic chemical (ATC) classification system. They were NMEs and their corresponding targets for the cardiovascular system, respiratory system, nerve system, general anti-infective systemic, genito-urinary system and sex hormones, alimentary tract and metabolisms, and antineoplastic and immunomodulating agents. To study the drug-target interaction on the systems level, we employed network topological analysis and multipartite network projections. As a result, the drug-target relations of different kinds of drugs were comprehensively characterized and global pictures of drug-target, drug-drug, and target-target interactions were visualized and analyzed from the perspective of network models.

FDA's proposed rules on patent listing requirements for new drug and 30-month stays on ANDA approval (proposed Oct. 24, 2002).

PubMed

Hui, Yuk Fung

2003-01-01

In order to close the loophole in the generic drug approval process that allows a brand name drug patent holder to delay or defeat generic drug application merely by technicality, the FDA recently proposed to modify its regulations. Those proposals affect the patent listing requirements of a new drug application, and the duration of time that a generic drug application could be put on hold in the event of a patent infringement suit. With the modified rules, the FDA expects to see an increase in the availability of generic drugs, which eventually will lead to lower drug costs. Ms. Hui discusses the contents of the proposed regulations and provides an analysis of the proposed rule's legal authority, implications on patent rights, and impact on the pharmaceutical industry.

Geographic Variation in Rosiglitazone Use Surrounding FDA Warnings in the Department of Veterans Affairs.

PubMed

Ahuja, Vishal; Sohn, Min-Woong; Birge, John R; Syverson, Chad; Budiman-Mak, Elly; Emanuele, Nicholas; Cooper, Jennifer M; Huang, Elbert S

2015-12-01

Geographic variation in the use of prescription drugs, particularly those deemed harmful by the FDA, may lead to variation in patient exposure to adverse drug events. One such drug is the glucose-lowering drug rosiglitazone, for which the FDA issued a safety alert on May 21, 2007, following the publication of a meta-analysis that suggested a 43% increase in the risk of myocardial infarction with the use of rosiglitazone. This alert was followed by a black box warning on August 14, 2007, that was updated 3 months later. While large declines have been documented in rosiglitazone use in clinical practice, little is known about how the use of rosiglitazone and other glucose-lowering drugs varied within the Department of Veterans Affairs (VA), surrounding the FDA alerts. Understanding this variation within integrated health care systems is essential to formulating policies that enhance patient protection and quality of care. To document variation in the use of rosiglitazone and other glucose- lowering drugs across 21 Veterans Integrated Service Networks (VISNs). We conducted a retrospective analysis of drug use patterns for all major diabetes drugs in a national cohort of 550,550 veterans with diabetes from 2003 to 2008. This included the time periods when rosiglitazone was added to (November 2003) and removed from (October 2007) the VA national formulary (VANF). We employed multivariable logistic regression models to statistically estimate the association between a patient's location and the patient's odds of using rosiglitazone. Aggregate rosiglitazone use increased monotonically from 7.7%, in the quarter it was added to the VANF (November 4, 2003), to a peak of 15.3% in the quarter when the FDA issued the safety alert. Rosiglitazone use decreased sharply afterwards, reaching 3.4% by the end of the study period (September 30, 2008). The use of pioglitazone, another glucose-lowering drug in the same class as rosiglitazone, was low when the FDA issued the safety alert (0.4%) but increased sharply afterwards, reaching 3.6% by the end of the study period. Insulin use increased monotonically; metformin use remained relatively flat; and sulfonylurea use exhibited a general declining trend throughout the study period. Statistically significant geographic variation was observed in rosiglitazone use throughout the study period. The prevalence range, defined as the range of minimum to maximum use across VISNs was 3.7%-12.4% in the first quarter (January 1 to March 31, 2003); 1.0%-5.5% in the last quarter of study period (July 1 to September 30, 2008); and reached a peak of 9.6%-25.5% in the quarter when the FDA safety alert was issued (April 1 to March 31, 2007). In 5 VISNs, peak rosiglitazone use occurred before the FDA issued the safety alert. The odds ratio of using rosiglitazone in a given VISN varied from 0.55 (95% CI = 0.52-0.59; VISN 10) to 1.58 (95% CI = 1.50-1.66; VISN 15), with VISN 1 being the reference region. The variation was higher in the periods after the FDA issued the safety alert. Much less variation was observed in the use of pioglitazone, metformin, sulfonylurea, and insulin. Our results show statistically significant variation in the way VISNs within the VA responded to the FDA alerts, suggesting a need for mechanisms that disseminate information and guidelines for drug use in a consistent and reliable manner. Further study of regions that adopted ideal practices earlier may provide lessons for regional leadership and practice culture within integrated health care systems.

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

FDA Kids' Home Page

MedlinePlus

... and Drug Administration A to Z Index Follow FDA En Español Search FDA Submit search Popular Content Home Food Drugs Medical ... 日本語 | فارسی | English FDA Accessibility Careers FDA Basics FOIA No FEAR Act ...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

36 CFR 13.980 - Other FDA closures and restrictions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Other FDA closures and... Preserve Frontcountry Developed Area (fda) § 13.980 Other FDA closures and restrictions. The Superintendent may prohibit or otherwise restrict activities in the FDA to protect public health, safety, or park...

21 CFR 314.102 - Communications between FDA and applicants.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Communications between FDA and applicants. 314.102... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.102 Communications between FDA and applicants. (a) General...

78 FR 18233 - Medical Devices; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... the right column: Section Remove Add 814.20 http://www.fda.gov/ http://www.fda.gov/ cdrh/devadvice.../ PremarketApproval PMA/default.htm. 822.7 http://www.fda.gov/ http://www.fda.gov/ cdrh/ombudsman/ AboutFDA/ dispute.html. CentersOffices/ OfficeofMedicalPr oductsandTobacco/ CDRH/ CDRHOmbudsman/ default.htm. 822.15...

Contrasting clinical evidence for market authorisation of cardio-vascular devices in Europe and the USA: a systematic analysis of 10 devices based on Austrian pre-reimbursement assessments.

PubMed

Wild, Claudia; Erdös, Judit; Zechmeister, Ingrid

2014-11-04

European medical device regulation is under scrutiny and will be re-regulated with stricter rules concerning requirements for clinical evidence for high-risk medical devices. It is the aim of this study to analyse the differences between Europe and USA in dealing with risks and benefits of new cardio-vascular devices. Since no information is available on clinical data used by the Notified Body for CE-marking, data from Austrian pre-reimbursement assessments close to European market approval were used as proxy and compared with clinical data available at time of market approval by FDA in the USA. 10 cardio-vascular interventions with 27 newly CE approved medical devices were analysed. The time lag between market authorisation in Europe and in the USA is 3 to 7 years. Only 7 CE-marked devices also hold a FDA market approval, 7 further devices are in FDA approved ongoing efficacy trials. For 4 of the CE-marked devices the FDA market application or the approval-trial was either suspended due to efficacy or safety concerns or the approval was denied. Evidence available at time of CE-marking are most often case-series or small feasibility RCTs, while large RCTs and only in rare cases prospective cohort studies are the basis of FDA approvals. Additionally, the FDA often requires post-approval studies for high-risk devices. Market authorisation based on mature clinical data deriving from larger RCTs and longer follow-ups do not only change the perspective on the risk-benefit ratio, but also secures real patient benefit and safety and assures payers of investing only in truly innovative devices.

Estimation from PET data of transient changes in dopamine concentration induced by alcohol: support for a non-parametric signal estimation method

NASA Astrophysics Data System (ADS)

Constantinescu, C. C.; Yoder, K. K.; Kareken, D. A.; Bouman, C. A.; O'Connor, S. J.; Normandin, M. D.; Morris, E. D.

2008-03-01

We previously developed a model-independent technique (non-parametric ntPET) for extracting the transient changes in neurotransmitter concentration from paired (rest & activation) PET studies with a receptor ligand. To provide support for our method, we introduced three hypotheses of validation based on work by Endres and Carson (1998 J. Cereb. Blood Flow Metab. 18 1196-210) and Yoder et al (2004 J. Nucl. Med. 45 903-11), and tested them on experimental data. All three hypotheses describe relationships between the estimated free (synaptic) dopamine curves (FDA(t)) and the change in binding potential (ΔBP). The veracity of the FDA(t) curves recovered by nonparametric ntPET is supported when the data adhere to the following hypothesized behaviors: (1) ΔBP should decline with increasing DA peak time, (2) ΔBP should increase as the strength of the temporal correlation between FDA(t) and the free raclopride (FRAC(t)) curve increases, (3) ΔBP should decline linearly with the effective weighted availability of the receptor sites. We analyzed regional brain data from 8 healthy subjects who received two [11C]raclopride scans: one at rest, and one during which unanticipated IV alcohol was administered to stimulate dopamine release. For several striatal regions, nonparametric ntPET was applied to recover FDA(t), and binding potential values were determined. Kendall rank-correlation analysis confirmed that the FDA(t) data followed the expected trends for all three validation hypotheses. Our findings lend credence to our model-independent estimates of FDA(t). Application of nonparametric ntPET may yield important insights into how alterations in timing of dopaminergic neurotransmission are involved in the pathologies of addiction and other psychiatric disorders.

Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

PubMed

Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

2015-01-01

Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

Trends in internet search activity, media coverage, and patient-centered health information after the FDA safety communications on surgical mesh for pelvic organ prolapse.

PubMed

Stone, Benjamin V; Forde, James C; Levit, Valerie B; Lee, Richard K; Te, Alexis E; Chughtai, Bilal

2016-11-01

In July 2011, the US Food and Drug Administration (FDA) issued a safety communication regarding serious complications associated with surgical mesh for pelvic organ prolapse, prompting increased media and public attention. This study sought to analyze internet search activity and news article volume after this FDA warning and to evaluate the quality of websites providing patient-centered information. Google Trends™ was utilized to evaluate search engine trends for the term "pelvic organ prolapse" and associated terms between 1 January 2004 and 31 December 2014. Google News™ was utilized to quantify the number of news articles annually under the term "pelvic organ prolapse." The search results for the term "pelvic organ prolapse" were assessed for quality using the Health On the Net Foundation (HON) certification. There was a significant increase in search activity from 37.42 in 2010 to 57.75 in 2011, at the time of the FDA communication (p = 0.021). No other annual interval had a statistically significant increase in search activity. The single highest monthly search activity, given the value of 100, was August 2011, immediately following the July 2011 notification, with the next highest value being 98 in July 2011. Linear regression analysis of news articles per year since the FDA communication revealed r 2  = 0.88, with a coefficient of 186. Quality assessment demonstrated that 42 % of websites were HON-certified, with .gov sites providing the highest quality information. Although the 2011 FDA safety communication on surgical mesh was associated with increased public and media attention, the quality of relevant health information on the internet remains of poor quality. Future quality assurance measures may be critical in enabling patients to play active roles in their own healthcare.

Development of fog detection algorithm using Himawari-8/AHI data at daytime

NASA Astrophysics Data System (ADS)

Han, Ji-Hye; Kim, So-Hyeong; suh, Myoung-Seok

2017-04-01

Fog is defined that small cloud water drops or ice particles float in the air and visibility is less than 1 km. In general, fog affects ecological system, radiation budget and human activities such as airplane, ship, and car. In this study, we developed a fog detection algorithm (FDA) consisted of four threshold tests of optical and textual properties of fog using satellite and ground observation data at daytime. For the detection of fog, we used satellite data (Himawari-8/AHI data) and other ancillary data such as air temperature from NWP data (over land), SST from OSTIA (over sea). And for validation, ground observed visibility data from KMA. The optical and textual properties of fog are normalized albedo (NAlb) and normalized local standard deviation (NLSD), respectively. In addition, differences between air temperature (SST) and fog top temperature (FTa(S)) are applied to discriminate the fog from low clouds. And post-processing is performed to detect the fog edge based on spatial continuity of fog. Threshold values for each test are determined by optimization processes based on the ROC analysis for the selected fog cases. Fog detection is performed according to solar zenith angle (SZA) because of the difference of available satellite data. In this study, we defined daytime when SZA is less than 85˚ . Result of FDA is presented by probability (0 ˜ 100 %) of fog through the weighted sum of each test result. The validation results with ground observed visibility data showed that POD and FAR are 0.63 ˜ 0.89 and 0.29 ˜ 0.46 according to the fog intensity and type, respectively. In general, the detection skills are better in the cases of intense and without high clouds than localized and weak fog. We are plan to transfer this algorithm to the National Meteorological Satellite Center of KMA for the operational detection of fog using GK-2A/AMI data which will be launched in 2018.

21 CFR 1.280 - How must you submit prior notice?

Code of Federal Regulations, 2010 CFR

2010-04-01

... to FDA. You must submit all prior notice information in the English language, except that an... Commercial System (ABI/ACS); or (2) The FDA PNSI at http://www.access.fda.gov. You must submit prior notice through the FDA Prior Notice System Interface (FDA PNSI) for articles of food imported or offered for...

78 FR 65329 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... Safety Testing of Sunlamp Products'' Form FDA 3632 ``Guide for Preparing Product Reports on Lasers and Products Containing Lasers'' Form FDA 3633''General Variance Request'' Form FDA 3634 ``Television Products Annual Report'' Form FDA 3635 ``Laser Light Show Notification'' Form FDA 3636 ``Guide for Preparing...

78 FR 35279 - Agency Information Collection Activities; Proposed Collection; Comment Request; Electronic Products

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-12

... Lasers and Products Containing Lasers'' FDA Form 3633 ``General Variance Request'' FDA Form 3634 ``Television Products Annual Report'' FDA Form 3635 ``Laser Light Show Notification'' FDA Form 3636 ``Guide for Preparing Annual Reports on Radiation Safety Testing of Laser and Laser Light Show Products'' FDA Form 3637...

75 FR 26964 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-13

... of Sunlamps and Sunlamp Products'' FDA Form 3632 ``Guide for Preparing Product Reports on Lasers and Products Containing Lasers'' FDA Form 3633 ``General Variance Request'' FDA Form 3634 ``Television Products Annual Report'' FDA Form 3635 ``Laser Light Show Notification'' FDA Form 3636 ``Guide for Preparing...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2012 CFR

2012-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2013 CFR

2013-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 2 2014-10-01 2014-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2010 CFR

2010-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 2 2013-10-01 2013-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2011 CFR

2011-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

21 CFR 314.106 - Foreign data.

Code of Federal Regulations, 2014 CFR

2014-04-01

... USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... without the need for an on-site inspection by FDA or, if FDA considers such an inspection to be necessary, FDA is able to validate the data through an on-site inspection or other appropriate means. Failure of...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

42 CFR 405.203 - FDA categorization of investigational devices.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 2 2012-10-01 2012-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational devices. (a) The FDA assigns a device with an FDA-approved IDE to one of two categories: (1) Experimental...

76 FR 30175 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-1999-D-0792] (Formerly FDA-1999-D-0792) Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial.... SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft guidance...

21 CFR 830.100 - FDA accreditation of an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA accreditation of an issuing agency. 830.100... (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA Accreditation of an Issuing Agency § 830.100 FDA... issuing agency. (b) Accreditation criteria. FDA may accredit an organization as an issuing agency, if the...

Heuristics to Facilitate Understanding of Discriminant Analysis.

ERIC Educational Resources Information Center

Van Epps, Pamela D.

This paper discusses the principles underlying discriminant analysis and constructs a simulated data set to illustrate its methods. Discriminant analysis is a multivariate technique for identifying the best combination of variables to maximally discriminate between groups. Discriminant functions are established on existing groups and used to…

Analysis of the Risks and Benefits of New Chemical Entities Approved by the US Food and Drug Administration (FDA) and Subsequently Withdrawn From the US Market.

PubMed

Patriarca, Peter A; Van Auken, R Michael; Kebschull, Scott A

2018-01-01

Benefit-risk evaluations of drugs have been conducted since the introduction of modern regulatory systems more than 50 years ago. Such judgments are typically made on the basis of qualitative or semiquantitative approaches, often without the aid of quantitative assessment methods, the latter having often been applied asymmetrically to place emphasis on benefit more so than harm. In an effort to preliminarily evaluate the utility of lives lost or saved, or quality-adjusted life-years (QALY) lost and gained as a means of quantitatively assessing the potential benefits and risks of a new chemical entity, we focused our attention on the unique scenario in which a drug was initially approved based on one set of data, but later withdrawn from the market based on a second set of data. In this analysis, a dimensionless risk to benefit ratio was calculated in each instance, based on the risk and benefit quantified in similar units. The results indicated that FDA decisions to approve the drug corresponded to risk to benefit ratios less than or equal to 0.136, and that decisions to withdraw the drug from the US market corresponded to risk to benefit ratios greater than or equal to 0.092. The probability of FDA approval was then estimated using logistic regression analysis. The results of this analysis indicated that there was a 50% probability of FDA approval if the risk to benefit ratio was 0.121, and that the probability approaches 100% for values much less than 0.121, and the probability approaches 0% for values much greater than 0.121. The large uncertainty in these estimates due to the small sample size and overlapping data may be addressed in the future by applying the methodology to other drugs.

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

77 FR 52036 - Privacy Act of 1974; Report of a New System of Records; FDA Records Related to Research...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0253] Privacy Act of 1974; Report of a New System of Records; FDA Records Related to Research Misconduct... Drug Administration's (FDA's) regulations for the protection of privacy, FDA is publishing notice of a...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 14.15 - Committees working under a contract with FDA.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Committees working under a contract with FDA. 14... under a contract with FDA. (a) FDA may enter into contracts with independent scientific or technical... contract initially executed with FDA after July 1, 1975, but which is determined not to be an advisory...

21 CFR 830.220 - Termination of FDA service as an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Termination of FDA service as an issuing agency... SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA as an Issuing Agency § 830.220 Termination of FDA service as an issuing agency. (a) FDA may end our services as an issuing agency if we...

21 CFR 60.34 - FDA action on petitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FDA action on petitions. 60.34 Section 60.34 Food... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... during the regulatory review period. FDA will publish its due diligence determination in the Federal...

How do the EMA and FDA decide which anticancer drugs make it to the market? A comparative qualitative study on decision makers' views.

PubMed

Tafuri, G; Stolk, P; Trotta, F; Putzeist, M; Leufkens, H G; Laing, R O; De Allegri, M

2014-01-01

The process leading to a regulatory outcome is guided by factors both related and unrelated to the data package, defined in this analysis as 'formal and informal factors', respectively. The aim of this qualitative study was to analyse which formal and informal factors drive the decision-making process of the European Medicines Agency (EMA) and Food and Drug Administration (FDA) regulators with regard to anticancer drugs, using in-depth semi-structured interviews with regulators of the two agencies. In line with the theory and practice of qualitative research, no set sample size was defined a priori. Respondent enrolment continued until saturation and redundancy were reached. Data were collected through means of in-depth semi-structured interviews conducted either in a face-to-face setting or via Skype(®) with each regulator. The interviews were audio-recorded and verbatim transcribed. The analysis was manually carried out on the transcribed text. Data were independently coded and categorized by two researchers. Interpretation of the findings emerged through a process of triangulation between the two. Seven EMA and six FDA regulators, who had extensive experience with making decisions about anticancer medicines, were interviewed between April and June 2012. There is an open dialogue between the FDA and EMA, with the two moving closer and exchanging information, not opinions. Differences in decision-making between the agencies may be due to a different evaluation of end points. Different interaction modalities with industry and patients represent an additional source of divergence with a potential impact on decision-making. The key message of our respondents was that the agencies manage uncertainty in a different way: unlike the EMA, the FDA has a prevailing attitude to take risks in order to guarantee quicker access to new treatments. Although formal factors are the main drivers for regulatory decisions, the influence of informal factors plays an important role in the drug evaluation process.

IDAAPM: integrated database of ADMET and adverse effects of predictive modeling based on FDA approved drug data.

PubMed

Legehar, Ashenafi; Xhaard, Henri; Ghemtio, Leo

2016-01-01

The disposition of a pharmaceutical compound within an organism, i.e. its Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) properties and adverse effects, critically affects late stage failure of drug candidates and has led to the withdrawal of approved drugs. Computational methods are effective approaches to reduce the number of safety issues by analyzing possible links between chemical structures and ADMET or adverse effects, but this is limited by the size, quality, and heterogeneity of the data available from individual sources. Thus, large, clean and integrated databases of approved drug data, associated with fast and efficient predictive tools are desirable early in the drug discovery process. We have built a relational database (IDAAPM) to integrate available approved drug data such as drug approval information, ADMET and adverse effects, chemical structures and molecular descriptors, targets, bioactivity and related references. The database has been coupled with a searchable web interface and modern data analytics platform (KNIME) to allow data access, data transformation, initial analysis and further predictive modeling. Data were extracted from FDA resources and supplemented from other publicly available databases. Currently, the database contains information regarding about 19,226 FDA approval applications for 31,815 products (small molecules and biologics) with their approval history, 2505 active ingredients, together with as many ADMET properties, 1629 molecular structures, 2.5 million adverse effects and 36,963 experimental drug-target bioactivity data. IDAAPM is a unique resource that, in a single relational database, provides detailed information on FDA approved drugs including their ADMET properties and adverse effects, the corresponding targets with bioactivity data, coupled with a data analytics platform. It can be used to perform basic to complex drug-target ADMET or adverse effects analysis and predictive modeling. IDAAPM is freely accessible at http://idaapm.helsinki.fi and can be exploited through a KNIME workflow connected to the database.Graphical abstractFDA approved drug data integration for predictive modeling.

What do providers want to know about opioid prescribing? A qualitative analysis of their questions.

PubMed

Cushman, Phoebe A; Liebschutz, Jane M; Hodgkin, Joseph G; Shanahan, Christopher W; White, Julie L; Hardesty, Ilana; Alford, Daniel P

2017-01-01

In 2012, the US Food and Drug Administration (FDA) responded to the opioid crisis with a Risk Evaluation and Mitigation Strategy, requiring manufacturers of extended-release/long-acting opioids to fund continuing medical education based on the "FDA Blueprint for Prescriber Education." Topics in the Blueprint are "Assessing Patients for Treatment," "Initiating Therapy, Modifying Dosing, and Discontinuing Use," "Managing Therapy," "Counseling Patients and Caregivers about Safe Use," "General Drug Information," and "Specific Drug Information." Based on the FDA Blueprint, Boston University School of Medicine's "Safe and Competent Opioid Prescribing Education" (SCOPE of Pain) offers live trainings for physicians and other prescribers. During trainings, participants submit written questions about the curriculum and/or their clinical experiences. The objective was to compare themes that arose from questions asked by SCOPE of Pain participants with content of the FDA Blueprint in order to evaluate how well the Blueprint answers prescribers' concerns. The authors conducted qualitative analyses of all 1309 questions submitted by participants in 29 trainings across 16 states from May 2013 to May 2015, using conventional content analysis to code the questions. Themes that emerged from participants' questions were then compared with the Blueprint. Most themes fell into the topic categories of the Blueprint. Five main themes diverged: Participants sought information on (1) safe alternatives to opioids, (2) overcoming barriers to safe opioid prescribing, (3) government regulations of opioid prescribing, (4) the role of marijuana in opioid prescribing, and (5) maintaining a positive provider-patient relationship while prescribing opioids. In addition to learning the mechanics of safe opioid prescribing, providers want to understand government regulations and effective patient communication skills. Aware of the limitations of opioids in managing chronic pain, providers seek advice on alternatives therapies. Future updates to the FDA Blueprint and other educational guidelines on opioid prescribing should address providers' additional questions.

Public Awareness of Uterine Power Morcellation Through US Food and Drug Administration Communications: Analysis of Google Trends Search Term Patterns

PubMed Central

Jamnagerwalla, Juzar; Markowitz, Melissa A; Thum, D Joseph; McCarty, Philip; Medendorp, Andrew R; Raz, Shlomo; Kim, Ja-Hong

2018-01-01

Background Uterine power morcellation, where the uterus is shred into smaller pieces, is a widely used technique for removal of uterine specimens in patients undergoing minimally invasive abdominal hysterectomy or myomectomy. Complications related to power morcellation of uterine specimens led to US Food and Drug Administration (FDA) communications in 2014 ultimately recommending against the use of power morcellation for women undergoing minimally invasive hysterectomy. Subsequently, practitioners drastically decreased the use of morcellation. Objective We aimed to determine the effect of increased patient awareness on the decrease in use of the morcellator. Google Trends is a public tool that provides data on temporal patterns of search terms, and we correlated this data with the timing of the FDA communication. Methods Weekly relative search volume (RSV) was obtained from Google Trends using the term “morcellation.” Higher RSV corresponds to increases in weekly search volume. Search volumes were divided into 3 groups: the 2 years prior to the FDA communication, a 1-year period following, and thereafter, with the distribution of the weekly RSV over the 3 periods tested using 1-way analysis of variance. Additionally, we analyzed the total number of websites containing the term “morcellation” over this time. Results The mean RSV prior to the FDA communication was 12.0 (SD 15.8), with the RSV being 60.3 (SD 24.7) in the 1-year after and 19.3 (SD 5.2) thereafter (P<.001). The mean number of webpages containing the term “morcellation” in 2011 was 10,800, rising to 18,800 during 2014 and 36,200 in 2017. Conclusions Google search activity about morcellation of uterine specimens increased significantly after the FDA communications. This trend indicates an increased public awareness regarding morcellation and its complications. More extensive preoperative counseling and alteration of surgical technique and clinician practice may be necessary. PMID:29699965

FDA Warns About Stem Cell Therapies

MedlinePlus

... For Consumers Consumer Updates FDA Warns About Stem Cell Therapies Share Tweet Linkedin Pin it More sharing ... the boxed section below for more advice. Stem Cell Uses and FDA Regulation The FDA has the ...

Federal Protection for Human Research Subjects: An Analysis of the Common Rule and Its Interactions with FDA Regulations and the HIPAA Privacy Rule

DTIC Science & Technology

2005-06-02

the interaction of the Privacy Rule and FDA regulations with the Common Rule. Appendix B CRS-12 20 Phocomelia Syndrome is a birth defect that may...linked to the birth defect phocomelia .20 ! Congress enacts the Drug Amendments of 1962 (P.L. 87-781), requiring researchers to obtain subjects...information about Phocomelia Syndrome, see [http://my.webmd.com/hw/health_guide_atoz/nord780.asp], visited Apr. 11, 2005. 178 Section 505(i) of the Food

The Conundrum of Online Prescription Drug Promotion Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

PubMed

Wanasika, Isaac

2016-03-26

This commentary discusses pertinent issues from Hyosun Kim's paper on online prescription drug promotion. The study is well-designed and the findings highlight some of the consequences of the Food and Drug Administration's (FDA's) decision to deregulate online advertising of prescription drugs. While Kim's findings confirm some of the early concerns, they also provide a perspective of implementation challenges in the ever-changing technological environment. © 2016 by Kerman University of Medical Sciences.

Methods for scalar-on-function regression.

PubMed

Reiss, Philip T; Goldsmith, Jeff; Shang, Han Lin; Ogden, R Todd

2017-08-01

Recent years have seen an explosion of activity in the field of functional data analysis (FDA), in which curves, spectra, images, etc. are considered as basic functional data units. A central problem in FDA is how to fit regression models with scalar responses and functional data points as predictors. We review some of the main approaches to this problem, categorizing the basic model types as linear, nonlinear and nonparametric. We discuss publicly available software packages, and illustrate some of the procedures by application to a functional magnetic resonance imaging dataset.

A Critical Analysis of Anti-Discrimination Law and Microaggressions in Academia

ERIC Educational Resources Information Center

Lukes, Robin; Bangs, Joann

2014-01-01

This article provides a critical analysis of microaggressions and anti-discrimination law in academia. There are many challenges for faculty claiming discrimination under current civil rights laws. Examples of microaggressions that fall outside of anti-discrimination law will be provided. Traditional legal analysis of discrimination will not end…

Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse.

PubMed

Swedberg, Michael D B

2016-01-01

Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit clear discriminative effects when tested against classical drugs of abuse in drug discrimination studies, and were not self-administered by rats. However, these compounds did cause salient discriminative effects of their own in animals trained to discriminate them from no drug. Therefore, from a safety pharmacology perspective, novel compounds that do not cause discriminative effects similar to classical drugs of abuse, may still cause psychoactive effects in humans and carry the potential to maintain drug abuse, suggesting that proactive investigation of drug abuse potential is warranted (Swedberg, 2013). These and other findings will be discussed, and the application of drug discrimination procedures beyond the typical standard application of testing novel compounds against known and well characterized reference drugs will be addressed. Copyright © 2016 Elsevier Inc. All rights reserved.

THPdb: Database of FDA-approved peptide and protein therapeutics.

PubMed

Usmani, Salman Sadullah; Bedi, Gursimran; Samuel, Jesse S; Singh, Sandeep; Kalra, Sourav; Kumar, Pawan; Ahuja, Anjuman Arora; Sharma, Meenu; Gautam, Ankur; Raghava, Gajendra P S

2017-01-01

THPdb (http://crdd.osdd.net/raghava/thpdb/) is a manually curated repository of Food and Drug Administration (FDA) approved therapeutic peptides and proteins. The information in THPdb has been compiled from 985 research publications, 70 patents and other resources like DrugBank. The current version of the database holds a total of 852 entries, providing comprehensive information on 239 US-FDA approved therapeutic peptides and proteins and their 380 drug variants. The information on each peptide and protein includes their sequences, chemical properties, composition, disease area, mode of activity, physical appearance, category or pharmacological class, pharmacodynamics, route of administration, toxicity, target of activity, etc. In addition, we have annotated the structure of most of the protein and peptides. A number of user-friendly tools have been integrated to facilitate easy browsing and data analysis. To assist scientific community, a web interface and mobile App have also been developed.

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare Department... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

21 CFR 830.210 - Eligibility for use of FDA as an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Eligibility for use of FDA as an issuing agency... SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA as an Issuing Agency § 830.210 Eligibility for use of FDA as an issuing agency. When FDA acts as an issuing agency, any labeler will be...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare DEPARTMENT... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false What expedited procedures apply when FDA initiates... procedures apply when FDA initiates a seizure action against a detained perishable food? If FDA initiates a... under this subpart, FDA will send the seizure recommendation to the Department of Justice (DOJ) within 4...

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare DEPARTMENT... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare DEPARTMENT... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

45 CFR 73a.735-201 - Control activity employees formerly associated with organizations subject to FDA regulation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... with organizations subject to FDA regulation. 73a.735-201 Section 73a.735-201 Public Welfare DEPARTMENT... with organizations subject to FDA regulation. (a) For a period of 1 year after FDA appointment, or... employed in a regulated organization within 1 year before FDA employment shall not participate in any...

21 CFR 1.393 - What information must FDA include in the detention order?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false What information must FDA include in the detention... Consumption How Does Fda Order A Detention? § 1.393 What information must FDA include in the detention order? (a) FDA must issue the detention order in writing, in the form of a detention notice, signed and...

Non-Ionizing Radiation Used in Microwave Ovens

MedlinePlus

... Human Services (HHS), U.S. Food and Drug Administration (FDA) FDA's Center for Devices and Radiological Health (CDRH) sets ... public health. These standards can be viewed on FDA's Code of Federal Regulations on Microwave Ovens . FDA ...

Hand-portable gas chromatography-ion mobility spectrometer for the determination of the freshness of fish

NASA Technical Reports Server (NTRS)

Snyder, A. Peter; Harden, Charles S.; Davis, Dennis M.; Shoff, Donald B.; Maswadeh, Waleed M.

1995-01-01

A hand-held, portable gas chromatography-ion mobility spectrometer (GC-IMS) device was used to detect the presence of volatile amine compounds in the headspace of decomposing fish. The Food and Drug Administration (FDA) largely relies on olfactory discrimination with respect to fresh and spoiled, frozen and unfrozen fish. The fish are delivered at ship docks on pallets, and each pallet of fish can range from 30-40 thousand dollars in value. Fresh fish were placed in a teflon bag and the direct headspace was interrogated. In the first three days, only low molecular weight volatile amines were detected. On the fourth day, a number of spectral signatures were observed which indicated the presence of 1,5-diaminopentane, cadaverine. Analyses typically took from 0.5-1 minute.

Incremental Revisions across the Life Span of Ophthalmic Devices after Initial Food and Drug Administration Premarket Approval, 1979-2015.

PubMed

Gopal, Anand D; Rathi, Vinay K; Teng, Christopher C; Del Priore, Lucian; Ross, Joseph S

2017-08-01

To characterize the frequency, nature, and regulatory mechanisms by which ophthalmic devices are iteratively modified after initial Food and Drug Administration (FDA) Premarket Approval (PMA). Retrospective cross-sectional analysis using publicly available FDA data. Ophthalmic devices initially approved via the FDA's PMA pathway between January 1, 1979 and December 31, 2015. We used the FDA's PMA Database to identify and characterize initial approvals and subsequent postmarket modifications to Class III ophthalmic devices. The FDA Recalls Database was used to identify associated safety events. Median iterated life span (timespan across which modifications occurred after initial PMA) and median number of supplements approved per device, by device type, and overall, stratified by regulatory pathway and modification type. Between 1979 and 2015, the FDA approved 168 original ophthalmic devices via the PMA pathway and 2813 subsequent modifications. More than one third (n = 64; 38%) of original approvals were intraocular lenses. Overall, devices underwent a median of 11 postmarket modifications (interquartile range [IQR], 3-24.8) across a median 10.0-year iterated life span (IQR, 4.1-16.7). The majority of devices (n = 144; 86%) underwent more than 1 postapproval modification, including more than 1 design modification (n = 84; 50%). The median number of changes altering device design or labeling was 3.5 (IQR, 1-9). Although manufacturing alterations (n = 834 of 2813; 30%) were the most frequent type of revision, changes involving device design (n = 667; 24%) and labeling (n = 417; 15%) were common. Recalled devices underwent more frequent postapproval modifications per year (median, 1.4; IQR, 0.7-2.3; mean, 1.5; 95% confidence interval, 1.1-1.9) in the period preceding recall than did nonrecalled devices (median, 0.5; IQR, 0.2-1.1; mean, 0.8; 95% confidence interval, 0.7-1.0) across their market approval period (P < 0.001). Most ophthalmic devices approved via the FDA's PMA pathway have undergone extensive revisions, including serial design and labeling changes, since their initial approvals, often without supporting clinical data. Ophthalmologists should take into consideration that cumulative revisions may render the clinical evidence that supported an original FDA approval less relevant to newer device models. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

OpenFDA: an innovative platform providing access to a wealth of FDA's publicly available data.

PubMed

Kass-Hout, Taha A; Xu, Zhiheng; Mohebbi, Matthew; Nelsen, Hans; Baker, Adam; Levine, Jonathan; Johanson, Elaine; Bright, Roselie A

2016-05-01

The objective of openFDA is to facilitate access and use of big important Food and Drug Administration public datasets by developers, researchers, and the public through harmonization of data across disparate FDA datasets provided via application programming interfaces (APIs). Using cutting-edge technologies deployed on FDA's new public cloud computing infrastructure, openFDA provides open data for easier, faster (over 300 requests per second per process), and better access to FDA datasets; open source code and documentation shared on GitHub for open community contributions of examples, apps and ideas; and infrastructure that can be adopted for other public health big data challenges. Since its launch on June 2, 2014, openFDA has developed four APIs for drug and device adverse events, recall information for all FDA-regulated products, and drug labeling. There have been more than 20 million API calls (more than half from outside the United States), 6000 registered users, 20,000 connected Internet Protocol addresses, and dozens of new software (mobile or web) apps developed. A case study demonstrates a use of openFDA data to understand an apparent association of a drug with an adverse event. With easier and faster access to these datasets, consumers worldwide can learn more about FDA-regulated products. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved.

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2013 CFR

2013-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

FDA Issues Final Guidance Clarifying FDA and EPA Jurisdiction over Mosquito-Related Products

EPA Pesticide Factsheets

FDA finalized guidance to provide information on FDA and EPA jurisdiction over the regulation of mosquito-related products intended to function as pesticides, including those products intended to function as pesticides

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2011 CFR

2011-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2010 CFR

2010-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

21 CFR 1.391 - Who approves a detention order?

Code of Federal Regulations, 2012 CFR

2012-04-01

... Fda Order A Detention? § 1.391 Who approves a detention order? An authorized FDA representative, i.e., the FDA District Director in whose district the article of food involved is located or an FDA official...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

21 CFR 1.379 - How long may FDA detain an article of food?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false How long may FDA detain an article of food? 1.379... Provisions § 1.379 How long may FDA detain an article of food? (a) FDA may detain an article of food for a... institute a seizure or injunction action. The authorized FDA representative may approve the additional 10...

The Food and Drug Administration advisory committees and panels: how they are applied to the drug regulatory process.

PubMed

Ciociola, Arthur A; Karlstadt, Robyn G; Pambianco, Daniel J; Woods, Karen L; Ehrenpreis, Eli D

2014-10-01

Food and Drug Administration (FDA) advisory panels and committees play a critical role in advising the FDA on the safety and efficacy of medical devices and drugs marketed in the US. Advisory panel recommendations are used by the FDA to make decisions regarding medical products. Currently, the FDA utilizes over 50 advisory panels that serve the three major FDA centers, including the Centers for Biologics, Drugs and Device Products. Members of an advisory panel typically include academicians, clinicians, consumers, patients, and industry representatives. The FDA establishes the schedules for advisory panel meetings on an annual basis and a panel usually meets several times a year for two consecutive days in Washington, DC. Typically, the advisory panel discusses issues highlighted by the FDA and is then asked to vote a response to the questions posed in advance by the FDA. Advisory panel recommendations have a strong influence on FDA's decision to approve a product, as evidenced by the 214 Advisory Panels FDA convened between January 2008 to November 2012, during which advisory panel members voted to approve the product (or use of the product) ∼74% of the time, with FDA ultimately approving the medical product (or use of the product) ∼79% of the time. The ACG membership are encouraged to consider serving the public's interest by participating in an FDA advisory panel utilizing their expertise for the evaluation of a new drug or medical device, and providing advice about whether the product should be sold in the US.

Fluorescein Diacetate Microplate Assay in Cell Viability Detection.

PubMed

Chen, Xi; Yang, Xiu-Ying; Fang, Lian-Hua; DU, Guan-Hua

2016-12-20

Objective To investigate the application of the fluorescein diacetate (FDA) microplate assay in cell viability detection. Methods Cells were seeded in a 96-well culture plate until detection. After incubated with FDA,the plate was detected by fluorescence microplate analyzer. The effects of FDA incubation duration,concentration,and other factors on the assay's accuracy and stability were assessed. We also compared the results of FDA with methyl thiazolyl(MTT) in terms of cell numbers and H 2 O 2 injury. Results Within 0-30 minutes,the fluorescence-cell number coefficient of FDA assay increased with duration and reached 0.99 in 27-30 minutes. The optimum concentration of final FDA in this study was 10-30 μg/ml. On cell viability detection,the result of FDA method was equivalent to MTT method. As to H 2 O 2 injury assay,the sensitivity of FDA method was superior to MTT on the higher concentration H 2 O 2 treatment due to a relative shorter duration for detection. Conclusion As a stable and reliable method,FDA is feasible for cell variability detection under varied conditions.

A Retrospective Evaluation of the Use of Mass Spectrometry in FDA Biologics License Applications

NASA Astrophysics Data System (ADS)

Rogstad, Sarah; Faustino, Anneliese; Ruth, Ashley; Keire, David; Boyne, Michael; Park, Jun

2017-05-01

The characterization sections of biologics license applications (BLAs) approved by the United States Food and Drug Administration (FDA) between 2000 and 2015 were investigated to examine the extent of the use of mass spectrometry. Mass spectrometry was found to be integral to the characterization of these biotherapeutics. Of the 80 electronically submitted monoclonal antibody and protein biotherapeutic BLAs included in this study, 79 were found to use mass spectrometric workflows for protein or impurity characterization. To further examine how MS is being used in successful BLAs, the applications were filtered based on the type and number of quality attributes characterized, the mass spectrometric workflows used (peptide mapping, intact mass analysis, and cleaved glycan analysis), the methods used to introduce the proteins into the gas phase (ESI, MALDI, or LC-ESI), and the specific types of instrumentation used. Analyses were conducted over a time course based on the FDA BLA approval to determine if any trends in utilization could be observed over time. Additionally, the different classes of protein-based biotherapeutics among the approved BLAs were clustered to determine if any trends could be attributed to the specific type of biotherapeutic.

Repositioning FDA Drugs as Potential Cruzain Inhibitors from Trypanosoma cruzi: Virtual Screening, In Vitro and In Vivo Studies.

PubMed

Palos, Isidro; Lara-Ramirez, Edgar E; Lopez-Cedillo, Julio Cesar; Garcia-Perez, Carlos; Kashif, Muhammad; Bocanegra-Garcia, Virgilio; Nogueda-Torres, Benjamin; Rivera, Gildardo

2017-06-18

Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi , which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. A computer-guided drug repositioning method was applied to identify potential FDA drugs (approved and withdrawn) as cruzain (Cz) inhibitors and trypanocidal effects were confirmed by in vitro and in vivo studies. 3180 FDA drugs were virtually screened using a structure-based approach. From a first molecular docking analysis, a set of 33 compounds with the best binding energies were selected. Subsequent consensus affinity binding, ligand amino acid contact clustering analysis, and ranked position were used to choose four known pharmacological compounds to be tested in vitro. Mouse blood samples infected with trypomastigotes from INC-5 and NINOA strains were used to test the trypanocidal effect of four selected compounds. Among these drugs, one fibrate antilipemic (etofyllin clofibrate) and three β-lactam antibiotics (piperacillin, cefoperazone, and flucloxacillin) showed better trypanocidal effects (LC 50 range 15.8-26.1 μg/mL) in comparison with benznidazole and nifurtimox (LC 50 range 33.1-46.7 μg/mL). A short-term in vivo evaluation of these compounds showed a reduction of parasitemia in infected mice (range 90-60%) at 6 h, but this was low compared to benznidazole (50%). This work suggests that four known FDA drugs could be used to design and obtain new trypanocidal agents.

An Assessment of Concerns Regarding New Regulatory Guidance for Combination Products: A Review of the Submissions Made to the FDA Regarding Their Proposed Draft New Guidance on Human Factors Studies for a Combination Product in an Abbreviated New Drug Application.

PubMed

Lance, Philip T; Greenaway, Ruth V; Edwards, Brian

2018-01-01

The US Food and Drug Administration (FDA) put out a call for comments on new draft guidance for industry "Comparative Analyses and Related Comparative Use Human Factors Studies for a Drug-Device Combination Product Submitted in an ANDA." This call for comments elicited 7 submissions from various organizations in the field of health care products. This article reports on a review conducted on these 7 submissions. The purpose of this review was to identify any commonalities across the different submissions and determine if there was consensus on any point or aspect of the draft guidance. To identify any commonalities, a heat map plotting the lines of the draft guidance that had raised a comment/suggestion was produced. Also, a thematic analysis was conducted on the comments/suggestions. In total the 7 submissions produced 137 suggestions. The heat map revealed that these suggestions did not focus on any single part of the guidance but were spread throughout the guidance. The thematic analysis conducted on the suggestions found a number of distinct trends. These trends were grouped into 10 primary themes, each with a number of subthemes. It was concluded that guidance from the FDA on this matter is warranted and would be appreciated. However, it was also concluded that based on the distinct trends identified in the suggestions, there are issues that the FDA may wish to consider before publishing their final guidance.

76 FR 1180 - FDA Transparency Initiative: Improving Transparency to Regulated Industry

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

...] FDA Transparency Initiative: Improving Transparency to Regulated Industry AGENCY: Food and Drug... the Transparency Initiative, the Food and Drug Administration (FDA) is announcing the availability of a report entitled ``FDA Transparency Initiative: Improving Transparency to Regulated Industry.'' The...

77 FR 70955 - FDA Actions Related to Nicotine Replacement Therapies and Smoking-Cessation Products; Report to...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-28

.... FDA-2012-N-1148] FDA Actions Related to Nicotine Replacement Therapies and Smoking-Cessation Products... comments. SUMMARY: The Food and Drug Administration (FDA) is announcing a 1-day public hearing to obtain...

Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

DTIC Science & Technology

2016-10-01

consensus meeting, with input from investigators in the Prostate Cancer Clinical Trials Consortium, FDA Office of Oncology Drug Products, FDA Study...Cancer Clinical Trials Consortium, FDA Office of Oncology Drug Products, FDA Study Endpoint and Label Development Team, and FDA Division of...Abstract. American Society of Clinical Oncology . Chicago IL, June 1-5, 2013. INVENTIONS, PATENTS AND LICENSES None 11 REPORTABLE OUTCOMES

Price analysis of multiple sclerosis disease-modifying therapies marketed in the United States.

PubMed

Bin Sawad, Aseel; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Turkistani, Fatema

2016-11-01

This study assessed trends in the average wholesale price (AWP) at the market entry of disease-modifying therapies (DMTs) approved by Food and Drug Administration (FDA) in the period 1987-2014. DMT regulatory information was derived from the FDA website. The AWPs per unit at market entry data were derived from the Red Book (Truven Health Analytics Inc.). The AWP history for each DMT was collected from its date of approval to 31 December 2014. The FDA approved label defined daily dose (DDD) for adult patients was obtained from FDA approved labels. The AWP per DDD and the AWP/DDD per year of therapy were computed. Descriptive statistics, Wilcoxon tests, t-test, and multiple linear regression were performed. The statistical significance level was set at 0.05. The FDA approved 12 multiple sclerosis (MS) DMTs, including five new drug applications (NDAs) and seven biologic license applications (BLAs) as of 31 December 2014. The FDA granted orphan designation to five DMTs. There was one DMT approved by the FDA in the 1980s, three in the 1990s, three in 2000s, and five in the period 2010-2014. The market entry inflation-adjusted AWP per DDD was $10.23 for the first DMT (mitoxantrone hydrochloride) that was approved in the 1980s. The median market entry inflation-adjusted AWP per DDD was $12.41 (interquartile range [IQR] = 4.51) for DMTs approved in the 1990s, $71.26 (IQR = 58.35) in the 2000s, and $172.56 (IQR = 84.97) in the period 2010-2014. The median AWP per DDD was statistically significantly different (p = 0.011) for orphan (median = $41.82, IQR = 56.077) compared to non-orphan drugs (median = $171.32, IQR = 199.29). Year of market entry was positively associated with DMT prices at US market entry (p = 0.01). The AWP per DDD for DMTs at market entry increased substantially over time. The increase in DMTs prices exceeded the general consumer price index.

A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Non-Small Cell Lung Cancer.

PubMed

Raju, G K; Gurumurthi, K; Domike, R; Kazandjian, D; Blumenthal, G; Pazdur, R; Woodcock, J

2016-12-01

Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analyses. There is much interest in quantifying regulatory approaches to benefit and risk. In this work the use of a quantitative benefit-risk analysis was applied to regulatory decision-making about new drugs to treat advanced non-small cell lung cancer (NSCLC). Benefits and risks associated with 20 US Food and Drug Administration (FDA) decisions associated with a set of candidate treatments submitted between 2003 and 2015 were analyzed. For benefit analysis, the median overall survival (OS) was used where available. When not available, OS was estimated based on overall response rate (ORR) or progression-free survival (PFS). Risks were analyzed based on magnitude (or severity) of harm and likelihood of occurrence. Additionally, a sensitivity analysis was explored to demonstrate analysis of systematic uncertainty. FDA approval decision outcomes considered were found to be consistent with the benefit-risk logic. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Pharmacotherapeutics of Intranasal Scopolamine: FDA Regulations and Procedures for Clinical Applications

NASA Technical Reports Server (NTRS)

Das, H.; Daniels, V. R.; Vaksman, Z.; Boyd, J. L.; Buckey, J. C.; Locke, J. P.; Putcha, L.

2007-01-01

Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during the early flight days of a space mission. Bioavailability of oral (PO) SMS medications is often low and highly variable; additionally, physiological changes in a microgravity environment exacerbate variability and decrease bioavailability. These factors prompted NASA to develop an intranasal dosage form of scopolamine (INSCOP) suitable for the treatment of SMS. However, to assure safety and efficacy of treatment in space, NASA physicians prescribe commercially available pharmaceutical products only. Development of a pharmaceutical preparation for clinical use must follow distinct clinical phases of testing, phase I through IV to be exact, before it can be approved by the FDA for approval for clinical use. After a physician sponsored Investigative New Drug (IND) application was approved by the FDA, a phase I clinical trial of INSCOP formulation was completed in normal human subjects and results published. The current project includes three phase II clinical protocols for the assessment of pharmacokinetics and pharmacodynamics (PK/PD), efficacy, and safety of INSCOP. Three clinical protocols that were submitted to FDA to accomplish the project objectives: 1) 002-A, a FDA Phase II dose ranging study with four dose levels between 0.1 and 0.4 mg in 12 subjects to assess PK/PD, 2) 002-B, a phase II clinical efficacy study in eighteen healthy subjects to compare efficacy of 0.2 (low dose) and 0.4 mg (high dose) INSCOP for prophylactic treatment of motion-induces (off-axis vertical rotation) symptoms, and (3) 002-C, a phase II clinical study with twelve subjects to determine bioavailability and pharmacodynamics of two doses (0.2 and 0.4 mg) of INSCOP in simulated microgravity, antiorthostatic bedrest. All regulatory procedures were competed that include certification for Good laboratory Procedures by Theradex , clinical documentation, personnel training, selection of clinical research operations contractor, data capturing and management, and annual reporting of results to FDA were successfully completed. Protocol 002-A was completed and sample and data analysis is currently in progress. Protocol 002-B is currently in progress at Dartmouth Hitchcock Medical Center and Protocol 002-C has been submitted to the FDA and will be implemented at the same contractor site as 002-A. An annual report was filed as required by FDA on the results of Protocol 002-A. Once all the three Phase II protocols are completed, a New Drug Administration application will be filed with FDA for Phase III clinical assessment and approval for marketing of the formulation. A commercial vendor will be identified for this phase. This is critical for making this available for treatment of SMS in astronauts and military personnel on duty. Once approved by FDA, INSCOP can be also used by civilian population for motion sickness associated with recreational travel and other ailments that require treatment with anticholinergic drugs.

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

21 CFR 314.103 - Dispute resolution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.103 Dispute resolution. (a) General. FDA is committed to resolving differences between applicants and FDA reviewing divisions with respect to technical requirements for applications or abbreviated...

Reflections on the US FDA's Warning on Direct-to-Consumer Genetic Testing.

PubMed

Yim, Seon-Hee; Chung, Yeun-Jun

2014-12-01

In November 2013, the US Food and Drug Administration (FDA) sent a warning letter to 23andMe, Inc. and ordered the company to discontinue marketing of the 23andMe Personal Genome Service (PGS) until it receives FDA marketing authorization for the device. The FDA considers the PGS as an unclassified medical device, which requires premarket approval or de novo classification. Opponents of the FDA's action expressed their concerns, saying that the FDA is overcautious and paternalistic, which violates consumers' rights and might stifle the consumer genomics field itself, and insisted that the agency should not restrict direct-to-consumer (DTC) genomic testing without empirical evidence of harm. Proponents support the agency's action as protection of consumers from potentially invalid and almost useless information. This action was also significant, since it reflected the FDA's attitude towards medical application of next-generation sequencing techniques. In this review, we followed up on the FDA-23andMe incident and evaluated the problems and prospects for DTC genetic testing.

Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys.

PubMed

Paule, M G; Li, M; Allen, R R; Liu, F; Zou, X; Hotchkiss, C; Hanig, J P; Patterson, T A; Slikker, W; Wang, C

2011-01-01

Previously our laboratory has shown that ketamine exposure (24h of clinically relevant anesthesia) causes significant increases in neuronal cell death in perinatal rhesus monkeys. Sensitivity to this ketamine-induced neurotoxicity was observed on gestational days 120-123 (in utero exposure via maternal anesthesia) and on postnatal days (PNDs) 5-6, but not on PNDs 35-37. In the present study, six monkeys were exposed on PND 5 or 6 to intravenous ketamine anesthesia to maintain a light surgical plane for 24h and six control animals were unexposed. At 7 months of age all animals were weaned and began training to perform a series of cognitive function tasks as part of the National Center for Toxicological Research (NCTR) Operant Test Battery (OTB). The OTB tasks used here included those for assessing aspects of learning, motivation, color discrimination, and short-term memory. Subjects responded for banana-flavored food pellets by pressing response levers and press-plates during daily (M-F) test sessions (50 min) and were assigned training scores based upon their individual performance. As reported earlier (Paule et al., 2009) beginning around 10 months of age, control animals significantly outperformed (had higher training scores than) ketamine-exposed animals for approximately the next 10 months. For animals now over 3 and one-half years of age, the cognitive impairments continue to manifest in the ketamine-exposed group as poorer performance in the OTB learning and color and position discrimination tasks, as deficits in accuracy of task performance, but also in response speed. There are also apparent differences in the motivation of these animals which may be impacting OTB performance. These observations demonstrate that a single 24-h episode of ketamine anesthesia, occurring during a sensitive period of brain development, results in very long-lasting deficits in brain function in primates and provide proof-of-concept that general anesthesia during critical periods of brain development can result in subsequent functional deficits. Supported by NICHD, CDER/FDA and NCTR/FDA. Published by Elsevier Inc.

Testing consumer perception of nutrient content claims using conjoint analysis.

PubMed

Drewnowski, Adam; Moskowitz, Howard; Reisner, Michele; Krieger, Bert

2010-05-01

The US Food and Drug Administration (FDA) proposes to establish standardized and mandatory criteria upon which front-of-pack (FOP) nutrition labelling must be based. The present study aimed to estimate the relative contribution of declared amounts of different nutrients to the perception of the overall 'healthfulness' of foods by the consumer. Protein, fibre, vitamin A, vitamin C, calcium and iron were nutrients to encourage. Total fat, saturated fat, cholesterol, total and added sugar, and sodium were the nutrients to limit. Two content claims per nutrient used the FDA-approved language. An online consumer panel (n 320) exposed to multiple messages (n 48) rated the healthfulness of each hypothetical food product. Utility functions were constructed using conjoint analysis, based on multiple logistic regression and maximum likelihood estimation. Consumer perception of healthfulness was most strongly driven by the declared presence of protein, fibre, calcium and vitamin C and by the declared total absence of saturated fat and sodium. For this adult panel, total and added sugar had lower utilities and contributed less to the perception of healthfulness. There were major differences between women and men. Conjoint analysis can lead to a better understanding of how consumers process information about the full nutrition profile of a product, and is a powerful tool for the testing of nutrient content claims. Such studies can help the FDA develop science-based criteria for nutrient profiling that underlies FOP and shelf labelling.

Telavancin for Acute Bacterial Skin and Skin Structure Infections, a Post Hoc Analysis of the Phase 3 ATLAS Trials in Light of the 2013 FDA Guidance

PubMed Central

Pushkin, Richard; Barriere, Steven L.; Corey, G. Ralph; Stryjewski, Martin E.

2015-01-01

Two phase 3 ATLAS trials demonstrated noninferiority of telavancin compared with vancomycin for complicated skin and skin structure infections. Data from these trials were retrospectively evaluated according to 2013 U.S. Food and Drug Administration (FDA) guidance on acute bacterial skin and skin structure infections. This post hoc analysis included patients with lesion sizes of ≥75 cm2 and excluded patients with ulcers or burns (updated all-treated population; n = 1,127). Updated day 3 (early) clinical response was defined as a ≥20% reduction in lesion size from baseline and no rescue antibiotic. Updated test-of-cure (TOC) clinical response was defined as a ≥90% reduction in lesion size, no increase in lesion size since day 3, and no requirement for additional antibiotics or significant surgical procedures. Day 3 (early) clinical responses were achieved in 62.6% and 61.0% of patients receiving telavancin and vancomycin, respectively (difference, 1.7%, with a 95% confidence interval [CI] of −4.0% to 7.4%). Updated TOC visit cure rates were similar for telavancin (68.0%) and vancomycin (63.3%), with a difference of 4.8% (95% CI, −0.7% to 10.3%). Adopting current FDA guidance, this analysis corroborates previous noninferiority findings of the ATLAS trials of telavancin compared with vancomycin. PMID:26248356

Current FDA directives for promoting public health

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hayes, A.H. Jr.

1982-03-01

The current directions of the FDA are outlined. The underlying philosophy of the FDA under the Reagan Administration is that both the private sector and the government must address the responsibilities to which they are best suited for the health-care system to work more efficiently. To facilitate this, FDA is conducting comprehensive reviews of FDA regulations and the drug-evaluation process. There are many dimensions to promoting public health, and the FDA alone cannot assure an adequate supply of safe and effective drugs. Innovative science and technology are needed to develop new drugs, followed by maximum potentiation (maximum good and leastmore » harm) after FDA approval. Hospital pharmacists have a role in maximizing the potential benefits of drugs through pharmacy and therapeutics committees. The current status of the pilot program for patient package inserts is described. The response at a recent hearing on the program indicates that the responsibility to protect the public health is shared by the government, health professions, industry, and the public. The FDA's campaign on sodium is based on that shared responsibility. By improving communication and building upon their common objections, both pharmacy and the FDA can do their jobs successfully.« less

Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis.

PubMed

Wallach, Joshua D; Egilman, Alexander C; Dhruva, Sanket S; McCarthy, Margaret E; Miller, Jennifer E; Woloshin, Steven; Schwartz, Lisa M; Ross, Joseph S

2018-05-24

To characterize postmarketing requirements for new drugs and biologics approved by the US Food and Drug Administration (FDA), and to examine rates and timeliness of registration, results reporting, and publication of required prospective cohort studies, registries, and clinical trials. Cross sectional analysis. Postmarketing requirements for all new drugs and biologics approved by the FDA between 1 January 2009 and 31 December 2012, with follow-up up to 15 November 2017. Postmarketing requirements and their characteristics known at the time of FDA approval, including FDA authority, study design, and study characteristics. Rates and timeliness of registration and results reporting on ClinicalTrials.gov and publication in peer reviewed journals of required prospective cohort studies, registries, and clinical trials. Between 2009 and 12, the FDA approved 97 new drugs and biologics for 106 indications with at least one postmarketing requirement at the time of first approval, for a total of 437 postmarketing requirements. Postmarket study descriptions were short (median word count 44 (interquartile range 29-71)) and often lacked information to determine an up to date progress (131 (30%)). 220 (50.3%) postmarketing requirements were for new animal or other studies (including pharmacokinetic studies); 134 (30.7%) were for prospective cohort studies, registries, and clinical trials; and 83 (19.0%) were for secondary analyses or follow-up studies. Of 110 clinical trials, 38 (34.5%), 44 (40.0%), 62 (56.4%), 66 (60.0%), and 98 (89.1%) did not report enough information to establish use of randomization, comparator type, allocation, outcome, and number of patients to be enrolled, respectively. Of 134 required prospective cohort studies, registries, and clinical trials, 102 (76.1%) were registered on ClinicalTrials.gov; of 50 registered and completed studies, 36 (72.0%) had reported results on ClinicalTrials.gov. Among 65 completed studies, 47 (72.3%) had either reported results or were published a median of 47 months (interquartile range 32-67) after FDA approval. 32 (68.1%) of these 47 studies did not report results publicly by the time of their original FDA report submission deadline. Postmarketing requirements for new drugs and biologics were often briefly described and did not contain enough information to characterize study designs. Approximately three quarters of postmarketing requirements for prospective cohort studies, registries, and clinical trials were registered on ClinicalTrials.gov, and nearly three quarters of completed studies reported results or were published, suggesting that at least a quarter of these required studies are not being publicly disseminated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

76 FR 38184 - Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Recall...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0439] Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Recall Regulations AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA...

The Effectiveness of Endoscopic Gastroplasty for Obesity Treatment According to FDA Thresholds: Systematic Review and Meta-Analysis Based on Randomized Controlled Trials.

PubMed

Madruga-Neto, Antonio Coutinho; Bernardo, Wanderley Marques; de Moura, Diogo Turiani Hourneaux; Brunaldi, Vitor Ottoboni; Martins, Rafael Krieger; Josino, Iatagan Rocha; de Moura, Eduardo Turiani Hourneaux; de Souza, Thiago Ferreira; Santo, Marco Aurélio; de Moura, Eduardo Guimarães Hourneaux

2018-06-16

Endoscopic bariatric therapies (EBTs) are promising alternatives to conventional surgery for obesity. The aim of this study is to compare efficacy and safety through a systematic review and meta-analysis of the endoscopic gastroplasty techniques versus conservative treatment. We searched MEDLINE, EMBASE, Cochrane CENTRAL, Lilacs/Bireme. Randomized controlled trials (RCTs) enrolling obese patients comparing endoscopic gastroplasty to sham or diet/exercise were considered eligible. Among 6014 records, three RCTs were selected for meta-analysis. The total sample was 459 patients (312 EBTs vs 147 control). Mean total body weight loss in the intervention group (IG) was 4.8% higher than the control group (CG) at 12 months (p = 0.01). The IG responder rate was 44.31% at 12 months. Therefore, the endoscopic gastroplasty is more effective than conservative therapies but do not achieve FDA thresholds.

Phase 2 Clinical Trial of AC105 (Mg/PEG) for Treatment of Acute Spinal Cord Injury (SCI)

DTIC Science & Technology

2015-12-01

initiation of 10 centers in the first 6 months, and an additional 10 centers over the next 6 months, the subject recruitment phase would have...Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10 Q11 Q12 FDA Approval, Planning & Rolling Initiation of Sites Active phase of study: 6 & 12 month follow-ups Data...analysis Reports The Proposed Milestones for the project were: 1. Month 3 – FDA approval of clinical protocol 2. Month 6 – First site initiation and IRB

Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: Teaching Drug Marketers How to Inform Better or Spin Better?

PubMed Central

Doran, Evan

2016-01-01

Hyosun Kim’s report "Trouble Spots in Online Direct to Consumer Prescription Drug Promotion: A content Analysis of FDA Warning Letters" aims to teach marketers how to avoid breaching current Food and Drug Administration (FDA) guidelines in their online drug promotion. While Kim hopes to minimise the potential for online promotion to misinform consumers and the study is carefully conducted, teaching drug marketers how to avoid the common mistakes in online drug promotion is more likely to make marketers more adept at spinning information than appropriately balancing it PMID:27239884

FDA actions against misleading or unsubstantiated economic and quality-of-life promotional claims: an analysis of warning letters and notices of violation.

PubMed

Stewart, Kate A; Neumann, Peter J

2002-01-01

The objective of this study was to understand the types of economic and quality-of-life promotional claims the FDA considers false or misleading. Publicly available FDA letters (n = 569) sent to pharmaceutical companies from 1997 through 2001 for inappropriate promotional claims were reviewed. A standard data collection form was developed, including six categories for economic violations and three for QOL violations. For QOL, only letters with explicit violations for false or misleading claims using the words "quality of life" or patient "well-being" were considered. Other information collected included type of regulatory letter and media in which violations were found. Twenty-eight (4.9%) letters cited false and/or misleading economic claims. The most common economic violation was "unsupported comparative claim of effectiveness, safety, or interchangeability" (n = 14). Twenty-eight (4.9%) letters cited QOL violations, of which four contained both economic and QOL violations. The most common QOL violation was "lack of substantial evidence for QOL claims" (n = 15). None of the FDA letters used the term "patient reported outcomes." Violations were found most frequently in brochure and Web site-based promotions. The body of evidence that is emerging illustrates how the FDA is regulating promotional material containing misleading or unsubstantiated economic and QOL claims. However, knowing what constitutes an appropriate claim remains challenging because there are no formal guidelines describing what constitutes a violation, nor what level of substantiating evidence is required. More guidance may be needed to ensure appropriate use of these claims in drug promotions.

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

76 FR 61709 - Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Form 3728...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0708] Agency Information Collection Activities; Proposed Collection; Comment Request; FDA Form 3728, Animal...: The Food and Drug Administration (FDA) is announcing an opportunity for public comment on the proposed...

21 CFR 830.120 - Responsibilities of an FDA-accredited issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Responsibilities of an FDA-accredited issuing... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA Accreditation of an Issuing Agency § 830.120 Responsibilities of an FDA-accredited issuing agency. To maintain its accreditation, an...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 314.108 - New drug product exclusivity.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and... investigation means that before or during the investigation, the applicant was named in Form FDA-1571 filed with FDA as the sponsor of the investigational new drug application under which the investigation was...

77 FR 51949 - Privacy Act, Exempt Record System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-28

.... FDA-2011-N-0252] Office of the Secretary 45 CFR Part 5b Privacy Act, Exempt Record System AGENCY... Drug Administration (FDA) of the Department of Health and Human Services (HHS) will be implementing a new system of records, 09-10-0020, ``FDA Records Related to Research Misconduct Proceedings, HHS/FDA...

21 CFR 314.96 - Amendments to an unapproved abbreviated application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... applicant on the same drug product formulation, unless the information has previously been submitted to FDA... and FDA determines that there may be bioequivalence issues or concerns with the product, FDA may...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

Internet Database Review: The FDA BBS.

ERIC Educational Resources Information Center

Tomaiuolo, Nicholas G.

1993-01-01

Describes the electronic bulletin board system (BBS) of the Food and Drug Administration (FDA) that is accessible through the Internet. Highlights include how to gain access; the menu-driven software; other electronic sources of FDA information; and adding value. Examples of the FDA BBS menu and the help screen are included. (LRW)

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

77 FR 14401 - Draft Guidance on Drug Safety Information-FDA's Communication to the Public; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2005-D-0339] Draft Guidance on Drug Safety Information--FDA's Communication to the Public; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2013 CFR

2013-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

78 FR 36194 - Draft Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-D-0490] Draft Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

10 CFR 35.7 - FDA, other Federal, and State requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false FDA, other Federal, and State requirements. 35.7 Section....7 FDA, other Federal, and State requirements. Nothing in this part relieves the licensee from complying with applicable FDA, other Federal, and State requirements governing radioactive drugs or devices. ...

21 CFR 812.30 - FDA action on applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA action on applications. 812.30 Section 812.30...) MEDICAL DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Application and Administrative Action § 812.30 FDA action on applications. (a) Approval or disapproval. FDA will notify the sponsor in writing of the date...

21 CFR 314.96 - Amendments to an unapproved abbreviated application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Abbreviated... applicant on the same drug product formulation, unless the information has previously been submitted to FDA... and FDA determines that there may be bioequivalence issues or concerns with the product, FDA may...

Pharmacokinetics of pediatric lopinavir/ritonavir tablets in children when administered twice daily according to FDA weight bands.

PubMed

Bastiaans, Diane E T; Forcat, Silvia; Lyall, Hermione; Cressey, Tim R; Hansudewechakul, Rawiwan; Kanjanavanit, Suparat; Noguera-Julian, Antoni; Königs, Christoph; Inshaw, Jamie R J; Chalermpantmetagul, Suwalai; Saïdi, Yacine; Compagnucci, Alexandra; Harper, Lynda M; Giaquinto, Carlo; Colbers, Angela P H; Burger, David M

2014-03-01

Lopinavir/ritonavir (LPV/r) pediatric tablets (100/25 mg) are approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) as part of combination antiretroviral therapy. Dosing is based on body weight bands or body surface area under FDA approval and only body surface area by the EMA. This can lead to a different recommended dose. In addition, weight band-based dosing has not been formally studied in the target population. We evaluated the pharmacokinetics (PK) of LPV/r in children, administered twice daily according to the FDA weight bands, using pediatric tablets. Fifty-three HIV-infected children were included in the PK substudy of the Paediatric European Network for the Treatment of AIDS 18 trial (KONCERT). In this study, children were randomized to receive LPV/r twice or once daily, according to FDA weight bands. A PK assessment was performed in 17, 16 and 20 children in the 15-25 kg, ≥ 25-35 kg and >35 kg weight band, respectively, while children took the tablets twice daily. Rich sampling was performed, and PK parameters were calculated by noncompartmental analysis. Given the high percentage of Asian children, it was also tested whether there was a difference in PK parameters between Asian and non-Asian children. For the total group, LPV geometric mean AUC0-12, Cmax and C12 were 106.9 h × mg/L, 12.0 mg/L and 4.9 mg/L, respectively. There were no significant differences in LPV PK parameters between the weight bands. In addition, weight was not found to be associated with variability in Cmax, C12 or AUC0-12 for the LPV PK parameters. FDA weight band-based dosing recommendations provide adequate exposure to LPV when using LPV/r pediatric tablets.

Change in Surgical Practice for Women With Leiomyomas After the U.S. Food and Drug Administration Morcellator Safety Communication.

PubMed

Clark, Nina M; Schembri, Michael; Jacoby, Vanessa L

2017-11-01

To evaluate the association between the U.S. Food and Drug Administration (FDA) communication discouraging use of power morcellators on changes in surgical practice for women with uterine leiomyomas. This is a cross-sectional study using data from 2013 to 2014 in the Healthcare Cost and Utilization Project State Inpatient and State Ambulatory Surgical Databases from Arizona, Florida, Kentucky, and New Jersey. Women with a diagnosis of leiomyomas who underwent hysterectomy or myomectomy were included in the analysis. Multivariable models were used to assess changes in the proportion of hysterectomies performed laparoscopically, vaginally, or by laparotomy in the 15 months before the FDA safety communication in April 2013 (January 2013 to March 2014) to the 9 months after the FDA communication (April to December 2014). Changes in the proportion of women who underwent myomectomy compared with hysterectomy were also evaluated during this time period. There were 77,637 hysterectomy and myomectomy cases analyzed from states with both inpatient and ambulatory surgery data; 59% of patients were outpatients. Overall, there was a 4% (95% CI 3.2-4.8%) decrease in the use of laparoscopic hysterectomy for treatment of uterine leiomyomas from 62% of all hysterectomies before the FDA communication on morcellation to 58% afterward. Changes in surgical practice were more pronounced in the inpatient compared with outpatient setting; inpatient laparoscopic hysterectomy decreased by 7% (95% CI 6.1-7.9%) from 24% to 17% of all hysterectomies with an accompanying increase in abdominal hysterectomy of 8% (95% CI 6.7-8.6%) from 71% to 79%. There were no significant changes in the proportion of women with leiomyomas who underwent myomectomy compared with hysterectomy. The FDA communication discouraging the use of power morcellators was associated with a decline in laparoscopy to perform hysterectomy, particularly in the inpatient setting. There was no change in the selection of myomectomy compared with hysterectomy for leiomyoma treatment after the FDA communication.

US Food and Drug Administration Clearance of Moderate-Risk Otolaryngologic Devices via the 510(k) Process, 1997-2016.

PubMed

Rathi, Vinay K; Gadkaree, Shekhar K; Ross, Joseph S; Kozin, Elliott D; Sethi, Rosh K; Naunheim, Matthew R; Puram, Sidharth V; Gray, Stacey T

2017-10-01

Objective The US Food and Drug Administration (FDA) clears moderate-risk devices via the 510(k) process based on substantial equivalence to previously cleared devices; evidence of safety and effectiveness is not required. We characterized the premarket evidence supporting FDA clearance of otolaryngologic devices. Study Design Retrospective cross-sectional analysis. Setting Publicly available FDA documents. Subjects and Methods Recently cleared (1997-2016) moderate-risk otolaryngologic devices were categorized by type (diagnostic/therapeutic), subspecialty, implantable designation (yes/no), and recall history (yes/no). Supporting evidence was categorized by type (clinical/nonclinical/none; nonclinical and clinical mutually inclusive) and public availability of nonclinical and clinical performance data (available/not provided/not applicable). Results Between 1997 and 2016, the FDA cleared 377 moderate-risk otolaryngologic devices. The majority were therapeutic (n = 240/377 [63.7%]) and otologic (n = 311/377 [82.5%]); roughly one-third (n = 121/377 [32.1%]) were implantable. Few (n = 10/377 [2.7%]) devices were subject to recall. FDA documents summarizing premarket evidence were accessible for two-thirds (n = 247/377 [65.5%]) of devices. Among these devices, one-quarter (n = 66/247 [26.7%]) were supported by clinical evidence. The majority (n = 177/247 [71.7%]) were supported by nonclinical evidence, although nearly one-quarter (n = 58/247 [23.5%]) were cleared without supporting evidence. Therapeutic devices were more often cleared without supporting evidence (therapeutic: n = 53/170 [31.2%]; diagnostic: n = 5/77 [6.5%]; P < .0001). Nonclinical and clinical performance data were rarely available (nonclinical: n = 49/247 [19.8%]; clinical: n = 32/247 [13.0%]) within public summaries. Conclusion The FDA cleared most moderate-risk otolaryngologic devices for marketing via the 510(k) process without clinical evidence of safety and effectiveness. Otolaryngologists should be aware of limitations in premarket evidence when considering the adoption of new devices into clinical practice.

Analysis of legal and scientific issues in court challenges to graphic tobacco warnings.

PubMed

Kraemer, John D; Baig, Sabeeh A

2013-09-01

Smoking is the leading preventable cause of death in the U.S., yet cigarette health warnings in the U.S. are among the weakest in the world. In 2011, the FDA issued regulations mandating that graphic warnings be displayed on every cigarette pack sold in the U.S. Almost immediately, the tobacco industry challenged the warnings on First Amendment grounds. In March 2013, the FDA withdrew the graphic warning mandate, choosing instead to pursue additional research and then issue requirements for a new set of warnings. These warnings almost certainly will be challenged by the tobacco industry. The current paper describes the legal standards that will be used to assess the warnings, and the empirical questions that must be answered in order to determine whether each standard has been met. The paper also identifies errors the FDA could make in choosing images to be evaluated that would cause the images to be unable to meet the standards, regardless of the scientific evidence the FDA can establish. To be on safest ground, the FDA should adopt images that depict factual health consequences of smoking and should avoid images that could be interpreted as opinions. The FDA will have a high likelihood of prevailing in legal challenges to the warnings if there is evidence demonstrating that graphic warnings are necessary to counter past industry deception or that graphic warnings affect smoking behavior better than textual warnings. Even without evidence of the impact of graphic warnings on behavior, strong evidence that they affect behavioral intent, and that intent predicts behavior, should be sufficient for the warnings to be upheld. Alternatively, evidence that graphic warnings lead to more accurate consumer assessment of smoking risks should also be sufficient. Copyright © 2013 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Oncologic Drugs Advisory Committee Recommendations and Approval of Cancer Drugs by the US Food and Drug Administration.

PubMed

Tibau, Ariadna; Ocana, Alberto; Anguera, Geòrgia; Seruga, Bostjan; Templeton, Arnoud J; Barnadas, Agustí; Amir, Eitan

2016-06-01

The US Food and Drug Administration (FDA) advisory committees influence decisions relating to the regulatory approval of drugs in the United States. Outside of the field of oncology, prosponsor voting bias has been observed among members with financial conflicts of interest (FCOIs). To explore factors associated with Oncologic Drugs Advisory Committee (ODAC) recommendations and the influence ODAC members' FCOIs on the drug approval process. Retrospective analysis of 82 ODAC meeting transcripts between January 2000 and December 2014. Analysis was restricted to meetings at which votes were cast relating to oncologic drugs. The influence of methodology of trials supporting approval and frequency and type of self-reported FCOIs of voting members was explored using logistic regression. ODAC recommendation for drug approval and subsequent FDA approval. Eighty-two transcripts of ODAC meetings between January 2000 and December 2014 were available for analysis. During the time period analyzed, ODAC members voted on 68 applications in 79 meetings (the remaining 3 meetings included voting questions regarding postmarketing safety or trial design). There was agreement between ODAC recommendations and final FDA approval; FDA approval was received for all 41 drugs that ODAC recommended approval. Additionally, the FDA approved 7 out of 41 agents that were not recommended for approval by ODAC (κ = 0.83). In 51 of 79 meetings, more than 1 trial was available to support the indication of a particular drug, and favorable ODAC recommendations were more likely when this was the case (odds ratio [OR], 1.82; 95% CI, 1.19-2.78; P = .01). Availability of randomized data did not appear to be important with selected single-arm phase 2 trials leading to recommendations for approval, especially in rare diseases. There has been a significant reduction in FCOIs over time (31 of 77 voting members [40%] in 2000 vs 0 of 20 voting members in 2014 [0%]; P < .001). Recommendations for approval were made in 28 of 47 meetings with members reporting FCOIs while among meetings with no reported FCOIs, recommendations for approval were made in 13 of 35 meetings (OR, 1.19; 95% CI, 0.97-1.46; P = .10). No significant association between ODAC recommendations and FDA approval was observed for members with FCOIs with the sponsor (OR, 1.79; 95% CI, 0.97-1.46; P = .19 and OR, 3.48; 95% CI, 0.84-14.35; P = .09, respectively) compared with members with FCOIs with competitors (OR, 1.06; 95% CI, 0.78-1.44; P = .72 and OR, 0.94; 95% CI, 0.69-1.28; P = .69, respectively). Availability of multiple trials is associated with higher odds of ODAC recommendation and drug approval. Availability of randomized data appears less important. Declaration of FCOIs among ODAC members was frequent during the time period of interest but has decreased significantly over time. There is no apparent association between FCOIs and ODAC recommendations and subsequent FDA approval.

Agenda: EDRN FDA Education Workshop — EDRN Public Portal

Cancer.gov

The purpose of this workshop was to open dialogue between FDA staff that provide oversight for review of in vitro diagnostic applications and EDRN scientists currently performing clinical validation studies on cancer biomarkers. Issues related to FDA review of diagnostic tests were presented by FDA personnel. Representatives from EDRN provided details on supporting data of their validation studies and the resources developed within EDRN to facilitate such research for FDA compliance. The agenda provided here provides links to the presentations by each speaker.

The debate on FDA reform: a view from the U.S. Senate. Food and Drug Administration.

PubMed

Baker, R

1995-09-01

The recently released concept paper on Food and Drug Administration (FDA) reform from Republican Senator, Nancy Kassebaum, is reviewed. Senator Kassebaum chairs the Senate Committee on Labor and Human Resources that will influence the Senate's action on FDA reform. The paper outlines the Senator's priorities for Congressional legislation on FDA reform in the following areas: the FDA mission and its accountability; creation of a Performance Review Panel and Industry Advisory Council; approval and access of products for seriously ill patients; the FDA's responsibility for good manufacturing practices; establishment of an Ombudsman Office for resolving disputes; dissemination of information on unapproved uses of approved products; and approval standards for new drugs.

Use of data mining at the Food and Drug Administration.

PubMed

Duggirala, Hesha J; Tonning, Joseph M; Smith, Ella; Bright, Roselie A; Baker, John D; Ball, Robert; Bell, Carlos; Bright-Ponte, Susan J; Botsis, Taxiarchis; Bouri, Khaled; Boyer, Marc; Burkhart, Keith; Condrey, G Steven; Chen, James J; Chirtel, Stuart; Filice, Ross W; Francis, Henry; Jiang, Hongying; Levine, Jonathan; Martin, David; Oladipo, Taiye; O'Neill, Rene; Palmer, Lee Anne M; Paredes, Antonio; Rochester, George; Sholtes, Deborah; Szarfman, Ana; Wong, Hui-Lee; Xu, Zhiheng; Kass-Hout, Taha

2016-03-01

This article summarizes past and current data mining activities at the United States Food and Drug Administration (FDA). We address data miners in all sectors, anyone interested in the safety of products regulated by the FDA (predominantly medical products, food, veterinary products and nutrition, and tobacco products), and those interested in FDA activities. Topics include routine and developmental data mining activities, short descriptions of mined FDA data, advantages and challenges of data mining at the FDA, and future directions of data mining at the FDA. Published by Oxford University Press on behalf of the American Medical Informatics Association 2015. This work is written by US Government employees and is in the public domain in the US.

A review of the FDA draft guidance document for software validation: guidance for industry.

PubMed

Keatley, K L

1999-01-01

A Draft Guidance Document (Version 1.1) was issued by the United States Food and Drug Administration (FDA) to address the software validation requirement of the Quality System Regulation, 21 CFR Part 820, effective June 1, 1997. The guidance document outlines validation considerations that the FDA regards as applicable to both medical device software and software used to "design, develop or manufacture" medical devices. The Draft Guidance is available at the FDA web site http:@www.fda.gov/cdrh/comps/swareval++ +.html. Presented here is a review of the main features of the FDA document for Quality System Regulation (QSR), and some guidance for its implementation in industry.

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

76 FR 31615 - Draft Guidance for Industry and FDA Staff: Commercially Distributed In Vitro Diagnostic Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0305] Draft Guidance for Industry and FDA Staff: Commercially Distributed In Vitro Diagnostic Products Labeled...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

77 FR 11553 - Draft Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0080... Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled ``FDA... that address nearly all aspects of the FDA approval and surveillance processes, including application...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 830.110 - Application for accreditation as an issuing agency.

Code of Federal Regulations, 2014 CFR

2014-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES UNIQUE DEVICE IDENTIFICATION FDA Accreditation of an Issuing Agency.... (1) An applicant seeking initial FDA accreditation as an issuing agency shall notify FDA of its desire to be accredited by sending a notification by email to [email protected]fda.hhs.gov, or by correspondence to...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

29 CFR 1987.108 - Role of Federal agencies.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) PROCEDURES FOR HANDLING RETALIATION COMPLAINTS UNDER SECTION 402 OF THE FDA FOOD SAFETY...) The FDA, if interested in a proceeding, may participate as amicus curiae at any time in the proceeding, at the FDA's discretion. At the request of the FDA, copies of all documents in a case must be sent to...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

76 FR 32367 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-1999-D-0742 (formerly Docket No. 1999D-4396)] Draft Guidance for Clinical Investigators, Industry, and FDA Staff...: Notice; correction. SUMMARY: The Food and Drug Administration (FDA) is correcting a notice that appeared...

78 FR 29141 - Center for Devices and Radiological Health Appeals Processes; Guidance for Industry and FDA Staff...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0893] Center for Devices and Radiological Health Appeals Processes; Guidance for Industry and FDA Staff... Administration (FDA) is announcing the availability of the guidance entitled ``Center for Devices and...

21 CFR 60.20 - FDA action on regulatory review period determinations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FDA action on regulatory review period... SERVICES GENERAL PATENT TERM RESTORATION Regulatory Review Period Determinations § 60.20 FDA action on regulatory review period determinations. (a) FDA will consult its records and experts to verify the dates...

21 CFR 801.57 - Discontinuation of legacy FDA identification numbers assigned to devices.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Discontinuation of legacy FDA identification... Device Identification § 801.57 Discontinuation of legacy FDA identification numbers assigned to devices... been assigned an FDA labeler code to facilitate use of NHRIC or NDC numbers may continue to use that...

78 FR 19492 - Draft Guidance for Industry on Formal Meetings Between FDA and Biosimilar Biological Product...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0286] Draft Guidance for Industry on Formal Meetings Between FDA and Biosimilar Biological Product Sponsors or... Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

75 FR 11893 - Food and Drug Administration Transparency Task Force; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247... Administration, HHS. ACTION: Notice; request for comments. SUMMARY: The Food and Drug Administration (FDA) is soliciting comments from interested persons on ways in which FDA can increase transparency between FDA and...

77 FR 71803 - Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0080... and Drug Administration (FDA) is announcing the availability of a guidance entitled ``FDA Oversight of... nearly all aspects of the FDA approval and surveillance processes, including application submission...

21 CFR 314.110 - Complete response letter to the applicant.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... response letter. FDA will send the applicant a complete response letter if the agency determines that we...) Complete review of data. A complete response letter reflects FDA's complete review of the data submitted in...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 812.42 - FDA and IRB approval.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA and IRB approval. 812.42 Section 812.42 Food... DEVICES INVESTIGATIONAL DEVICE EXEMPTIONS Responsibilities of Sponsors § 812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both...

21 CFR 314.125 - Refusal to approve an application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications... the application under section 505(d) of the act, if: (1) FDA sends the applicant a complete response... question of whether the application is approvable; and (3) FDA finds that any of the reasons given in...

21 CFR 807.100 - FDA action on a premarket notification.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA action on a premarket notification. 807.100... IMPORTERS OF DEVICES Premarket Notification Procedures § 807.100 FDA action on a premarket notification. (a) After review of a premarket notification, FDA will: (1) Issue an order declaring the device to be...

21 CFR 60.10 - FDA assistance on eligibility.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FDA assistance on eligibility. 60.10 Section 60.10... TERM RESTORATION Eligibility Assistance § 60.10 FDA assistance on eligibility. (a) Upon written request from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in...

76 FR 41506 - Draft Guidance for Industry and FDA Staff on In Vitro Companion Diagnostic Devices; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0215] Draft Guidance for Industry and FDA Staff on In Vitro Companion Diagnostic Devices; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is...

76 FR 56205 - Request for Notification From Industry Organizations Interested in Participating in the Selection...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

... Products Scientific Advisory Committee, notify FDA in writing. FDA is also requesting nominations for... letters stating interest in participating in the selection process to FDA by October 12, 2011 (see... candidates should be sent to FDA by October 12, 2011. ADDRESSES: All letters of interest and nominations...

Regulating (for the benefit of) future persons: a different perspective on the FDA's jurisdiction to regulate human reproductive cloning.

PubMed

Javitt, Gail H; Hudson, Kathy

2003-01-01

The Food and Drug Administration (FDA) has taken the position that human reproductive cloning falls within its regulatory jurisdiction. This position has been subject to criticism on both procedural and substantive grounds. Some have contended that the FDA has failed to follow administrative law principles in asserting its jurisdiction, while others claim the FDA is ill suited to the task of addressing the ethical and social implications of human cloning. This Article argues, that, notwithstanding these criticisms, the FDA could plausibly assert jurisdiction over human cloning as a form of human gene therapy, an area in which the FDA is already regarded as having primary regulatory authority. Such an assertion would require that the FDA's jurisdiction extend to products affecting future persons, i.e., those not yet born. This Article demonstrates, for the first time, that such jurisdiction was implicit in the enactment of the 1962 Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act and that the FDA has historically relied on such authority in promulgating regulations for drugs and devices.

EBOLA and FDA: reviewing the response to the 2014 outbreak, to find lessons for the future

PubMed Central

Largent, Emily A.

2016-01-01

Abstract In 2014, West Africa confronted the most severe outbreak of Ebola virus disease (EVD) in history. At the onset of the outbreak—as now—there were no therapies approved by the U.S. Food and Drug Administration (FDA) for prevention of, post-exposure prophylaxis against, or treatment of EVD. As a result, the outbreak spurred interest in developing novel treatments, sparked calls to use experimental interventions in the field, and highlighted challenges to the standard approach to FDA approval of new drugs. Although the outbreak was geographically centered in West Africa, it showcased FDA's global role in drug development, approval, and access. FDA's response to EVD highlights the panoply of agency powers and demonstrates the flexibility of FDA's regulatory framework. This paper evaluates the strengths and weaknesses of FDA's response and makes policy recommendations regarding how FDA should respond to new and re-emerging public health threats. In particular, it argues that greater emphasis should be placed on drug development in interoutbreak periods and on assuring access to approved products. The current pandemic of Zika virus infection is but one example of an emerging health threat that will require FDA involvement in order to achieve a successful response. PMID:28852537

A Critical Review of Methods to Evaluate the Impact of FDA Regulatory Actions

PubMed Central

Briesacher, Becky A.; Soumerai, Stephen B.; Zhang, Fang; Toh, Sengwee; Andrade, Susan E.; Wagner, Joann L.; Shoaibi, Azadeh; Gurwitz, Jerry H.

2013-01-01

Purpose To conduct a synthesis of the literature on methods to evaluate the impacts of FDA regulatory actions, and identify best practices for future evaluations. Methods We searched MEDLINE for manuscripts published between January 1948 and August 2011 that included terms related to FDA, regulatory actions, and empirical evaluation; the review additionally included FDA-identified literature. We used a modified Delphi method to identify preferred methodologies. We included studies with explicit methods to address threats to validity, and identified designs and analytic methods with strong internal validity that have been applied to other policy evaluations. Results We included 18 studies out of 243 abstracts and papers screened. Overall, analytic rigor in prior evaluations of FDA regulatory actions varied considerably; less than a quarter of studies (22%) included control groups. Only 56% assessed changes in the use of substitute products/services, and 11% examined patient health outcomes. Among studies meeting minimal criteria of rigor, 50% found no impact or weak/modest impacts of FDA actions and 33% detected unintended consequences. Among those studies finding significant intended effects of FDA actions, all cited the importance of intensive communication efforts. There are preferred methods with strong internal validity that have yet to be applied to evaluations of FDA regulatory actions. Conclusions Rigorous evaluations of the impact of FDA regulatory actions have been limited and infrequent. Several methods with strong internal validity are available to improve trustworthiness of future evaluations of FDA policies. PMID:23847020

Association of the FDA Amendment Act with trial registration, publication, and outcome reporting.

PubMed

Phillips, Adam T; Desai, Nihar R; Krumholz, Harlan M; Zou, Constance X; Miller, Jennifer E; Ross, Joseph S

2017-07-18

Selective clinical trial publication and outcome reporting has the potential to bias the medical literature. The 2007 Food and Drug Administration (FDA) Amendment Act (FDAAA) mandated clinical trial registration and outcome reporting on ClinicalTrials.gov, a publicly accessible trial registry. Using publicly available data from ClinicalTrials.gov, FDA documents, and PubMed, we determined registration, publication, and reporting of findings for all efficacy trials supporting FDA approval of new drugs for cardiovascular disease and diabetes between 2005 and 2014, before and after the FDAAA. For published trials, we compared the published interpretation of the findings (positive, equivocal, or negative) with the FDA reviewer's interpretation. Between 2005 and 2014, the FDA approved 30 drugs for 32 indications of cardiovascular disease (n = 17) and diabetes (n = 15) on the basis of 183 trials (median per indication 5.7 (IQR, 3-8)). Compared with pre FDAAA, post-FDAAA studies were more likely to be registered (78 of 78 (100%) vs 73 of 105 (70%); p < 0.001), to be published (76 of 78 (97%) vs 93 of 105 (89%); p = 0.03), and to present findings concordant with the FDA reviewer's interpretation (74 of 76 (97%) vs 78 of 93 (84%); p = 0.004). Pre FDAAA, the FDA reviewer interpreted 80 (76%) trials as positive and 91 (98%) were published as positive. Post FDAAA, the FDA reviewer interpreted 71 (91%) trials as positive and 71 (93%) were published as positive. FDAAA was associated with increased registration, publication, and FDA-concordant outcome reporting for trials supporting FDA approval of new drugs for cardiovascular disease and diabetes.

Spin in RCTs of anxiety medication with a positive primary outcome: a comparison of concerns expressed by the US FDA and in the published literature.

PubMed

Beijers, Lian; Jeronimus, Bertus F; Turner, Erick H; de Jonge, Peter; Roest, Annelieke M

2017-03-29

This study aimed to determine the presence of spin in papers on positive randomised clinical trials (RCTs) of antidepressant medication for anxiety disorders by comparing concerns expressed in the Food and Drug Administration (FDA) reviews with those expressed in the published paper. For every positive anxiety medication trial with a matching publication (n=41), two independent reviewers identified the concerns raised in the US FDA reviews and those in the published literature. Spin was identified when concerns or limitations were expressed by the FDA (about the efficacy of the study drug) but not in the corresponding published paper. Concerns mentioned in the papers but not by the FDA were scored as 'non-FDA' concerns. Only six out of 35 (17%) of the FDA concerns pertaining to drug efficacy were reported in the papers. Two papers mentioned a concern that fit the FDA categories, but was not mentioned in the corresponding FDA review. Eighty-seven non-FDA concerns were counted, which often reflected general concerns or concerns related to the study design. Results indicate the presence of substantial spin in the clinical trial literature on drugs for anxiety disorders. In papers describing RCTs on anxiety medication, the concerns raised by the authors differed from those raised by the FDA. Published papers mentioned a large number of generic concerns about RCTs, such as a lack of long-term research and limited generalisability, while they mentioned few concerns about drug efficacy. These results warrant the promotion of independent statistical review, reporting of patient-level data, more study of spin, and an increased expectation that authors report FDA concerns. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Enhancing the incorporation of the patient's voice in drug development and evaluation.

PubMed

Chalasani, Meghana; Vaidya, Pujita; Mullin, Theresa

2018-01-01

People living with a condition are uniquely positioned to inform the understanding of the therapeutic context for drug development and evaluation. In 2012, the U.S. Food and Drug Administration (FDA) established the Patient-Focused Drug Development (PFDD) initiative to more systematically obtain the patient perspective on specific diseases and their currently available treatments. PFDD meetings are unique among FDA public meetings, with a format designed to engage patients and elicit their perspectives on two topic areas: (1) the most significant symptoms of their condition and the impact of the condition on daily life; and, (2) their current approaches to treatment. FDA has conducted 24 disease-specific PFDD meetings to date. The lessons learned from PFDD meetings range from experiences common across rare diseases to more disease specific experiences that matter most to patients. FDA recognizes that FDA-led PFDD meetings alone cannot address the gaps in information on the patient perspective. Patient-focused drug development is an ongoing effort and FDA looks forward to the next steps in advancing the science and the utilization of patient input throughout drug development and evaluation. The U.S. Food and Drug Administration (FDA) has multiple mechanisms for its regulators and staff to interact with patients -- but none quite like its novel Patient-Focused Drug Development (PFDD) initiative. FDA established the PFDD initiative to more systematically obtain the patient perspective on specific diseases and their currently available treatments. Since the initiative's inception in 2012, FDA has held 24 PFDD meetings, covering a range of disease areas and hearing directly from thousands of patients and caregivers. FDA's PFDD meetings have also provided key stakeholders, including patient advocates, researchers, drug developers, healthcare providers, and other government officials, an opportunity to hear the patient's voice. The lessons learned include but are not limited to specific experiences that matter most to patients, patient perspectives on meaningful treatment benefits and how patients want to be engaged in the drug development process. FDA recognizes that FDA-led PFDD meetings alone cannot address the gaps in information on the patient perspective. Further enhancing the incorporation of the patient's voice in drug development and evaluation continues to be a priority for FDA.

Association of Attorney Advertising and FDA Action with Prescription Claims: A Time Series Segmented Regression Analysis.

PubMed

Tippett, Elizabeth C; Chen, Brian K

2015-12-01

Attorneys sponsor television advertisements that include repeated warnings about adverse drug events to solicit consumers for lawsuits against drug manufacturers. The relationship between such advertising, safety actions by the US Food and Drug Administration (FDA), and healthcare use is unknown. To investigate the relationship between attorney advertising, FDA actions, and prescription drug claims. The study examined total users per month and prescription rates for seven drugs with substantial attorney advertising volume and FDA or other safety interventions during 2009. Segmented regression analysis was used to detect pre-intervention trends, post-intervention level changes, and changes in post-intervention trends relative to the pre-intervention trends in the use of these seven drugs, using advertising volume, media hits, and the number of Medicare enrollees as covariates. Data for these variables were obtained from the Center for Medicare and Medicaid Services, Kantar Media, and LexisNexis. Several types of safety actions were associated with reductions in drug users and/or prescription rates, particularly for fentanyl, varenicline, and paroxetine. In most cases, attorney advertising volume rose in conjunction with major safety actions. Attorney advertising volume was positively correlated with prescription rates in five of seven drugs, likely because advertising volume began rising before safety actions, when prescription rates were still increasing. On the other hand, attorney advertising had mixed associations with the number of users per month. Regulatory and safety actions likely reduced the number of users and/or prescription rates for some drugs. Attorneys may have strategically chosen to begin advertising adverse drug events prior to major safety actions, but we found little evidence that attorney advertising reduced drug use. Further research is needed to better understand how consumers and physicians respond to attorney advertising.

FDA-Required Tobacco Product Inserts & Onserts–and the First Amendment.

PubMed

Lindblom, Eric N; Berman, Micah L; Thrasher, James F

In 2012, a federal court of appeals struck down an FDA rule requiring graphic health warnings on cigarettes as violating First Amendment commercial speech protections. Tobacco product inserts and onserts can more readily avoid First Amendment constraints while delivering more extensive information to tobacco users, and can work effectively to support and encourage smoking cessation. This paper examines FDA’s authority to require effective inserts and onserts and shows how FDA could design and support them to avoid First Amendment problems. Through this process, the paper offers helpful insights regarding how key Tobacco Control Act provisions can and should be interpreted and applied to follow and promote the statute’s purposes and objectives. The paper’s rigorous analysis of existing First Amendment case law relating to compelled commercial speech also provides useful guidance for any government efforts either to compel product disclosures or to require government messaging in or on commercial products or their advertising, whether done for remedial, purely informational, or behavior modification purposes.

Data Sets Representative of the Structures and Experimental Properties of FDA-Approved Drugs.

PubMed

Douguet, Dominique

2018-03-08

Presented here are several data sets that gather information collected from the labels of the FDA approved drugs: their molecular structures and those of the described active metabolites, their associated pharmacokinetics and pharmacodynamics data, and the history of their marketing authorization by the FDA. To date, 1852 chemical structures have been identified with a molecular weight less than 2000 of which 492 are or have active metabolites. To promote the sharing of data, the original web server was upgraded for browsing the database and downloading the data sets (http://chemoinfo.ipmc.cnrs.fr/edrug3d). It is believed that the multidimensional chemistry-oriented collections are an essential resource for a thorough analysis of the current drug chemical space. The data sets are envisioned as being used in a wide range of endeavors that include drug repurposing, drug design, privileged structures analyses, structure-activity relationship studies, and improving of absorption, distribution, metabolism, and elimination predictive models.

Evaluating oversight of human drugs and medical devices: a case study of the FDA and implications for nanobiotechnology.

PubMed

Paradise, Jordan; Tisdale, Alison W; Hall, Ralph F; Kokkoli, Efrosini

2009-01-01

This article evaluates the oversight of drugs and medical devices by the U.S. Food and Drug Administration (FDA) using an integration of public policy, law, and bioethics approaches and employing multiple assessment criteria, including economic, social, safety, and technological. Criteria assessment and expert elicitation are combined with existing literature, case law, and regulations in an integrative historical case studies approach. We then use our findings as a tool to explore possibilities for effective oversight and regulatory mechanisms for nanobiotechnology. Section I describes oversight mechanisms for human drugs and medical devices and presents current nanotechnology products. Section II describes the results of expert elicitation research. Section III highlights key criteria and relates them to the literature and larger debate. We conclude with broad lessons for the oversight of nanobiotechnology informed by Sections I-III in order to provide useful analysis from multiple disciplines and perspectives to guide discussions regarding appropriate FDA oversight.

Demise of Polymerase Chain Reaction/Electrospray Ionization-Mass Spectrometry as an Infectious Diseases Diagnostic Tool.

PubMed

Özenci, Volkan; Patel, Robin; Ullberg, Måns; Strålin, Kristoffer

2018-01-18

Although there are several US Food and Drug Administration (FDA)-approved/cleared molecular microbiology diagnostics for direct analysis of patient samples, all are single target or panel-based tests. There is no FDA-approved/cleared diagnostic for broad microbial detection. Polymerase chain reaction (PCR)/electrospray ionization-mass spectrometry (PCR/ESI-MS), commercialized as the IRIDICA system (Abbott) and formerly PLEX-ID, had been under development for over a decade and had become CE-marked and commercially available in Europe in 2014. Capable of detecting a large number of microorganisms, it was under review at the FDA when, in April 2017, Abbott discontinued it. This turn of events represents not only the loss of a potential diagnostic tool for infectious diseases but may be a harbinger of similar situations with other emerging and expensive microbial diagnostics, especially genomic tests. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Who's guarding what? A poststructural feminist analysis of gardasil discourses.

PubMed

Thompson, Marie

2010-03-01

In May 2006 the Gardasil vaccine was approved for implementation in the United States to prohibit the spread of four strains of the human papillomavirus (HPV) that can lead to cervical cancer. Through a poststructural feminist reading, I critique ideologies at play throughout the Food and Drug Administration (FDA) approval hearing for this vaccine. I explore the conditions that gave rise to the adoption of the Gardasil vaccine as evidenced in the hearing transcript, and probe contradictions between choices the FDA enacted for the feminine body with those recommendations from lead scientists of Merck that urged the inclusion of males in the vaccination process. Along the way, I respond to appeals from scholars to address matters of health policy formation and implementation as critical and underexplored dimensions of health communication. I offer a vision that makes way for proactive engagement of males in reproductive and sexual health, particularly as the FDA delayed vaccine approval for males until 2009.

CDC Vital Signs: Preventing Norovirus Outbreaks

MedlinePlus

... source of norovirus outbreaks using genome sequencing and analysis. State and local governments can Adopt and enforce all provisions of the FDA model Food Code to better safeguard food. Investigate norovirus outbreaks ...

Legitimating Racial Discrimination: Emotions, Not Beliefs, Best Predict Discrimination in a Meta-Analysis

PubMed Central

Talaska, Cara A.; Chaiken, Shelly

2013-01-01

Investigations of racial bias have emphasized stereotypes and other beliefs as central explanatory mechanisms and as legitimating discrimination. In recent theory and research, emotional prejudices have emerged as another, more direct predictor of discrimination. A new comprehensive meta-analysis of 57 racial attitude-discrimination studies finds a moderate relationship between overall attitudes and discrimination. Emotional prejudices are twices as closely related to racial discrimination as stereotypes and beliefs are. Moreover, emotional prejudices are closely related to both observed and self-reported discrimination, whereas stereotypes and beliefs are related only to self-reported discrimination. Implications for justifying discrimination are discussed. PMID:24052687

An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L↑N↑L PR mutant

NASA Astrophysics Data System (ADS)

Sanusi, Zainab K.; Govender, Thavendran; Maguire, Glenn E. M.; Maseko, Sibusiso B.; Lin, Johnson; Kruger, Hendrik G.; Honarparvar, Bahareh

2018-03-01

The aspartate protease of the human immune deficiency type-1 virus (HIV-1) has become a crucial antiviral target in which many useful antiretroviral inhibitors have been developed. However, it seems the emergence of new HIV-1 PR mutations enhances drug resistance, hence, the available FDA approved drugs show less activity towards the protease. A mutation and insertion designated L38L↑N↑L PR was recently reported from subtype of C-SA HIV-1. An integrated two-layered ONIOM (QM:MM) method was employed in this study to examine the binding affinities of the nine HIV PR inhibitors against this mutant. The computed binding free energies as well as experimental data revealed a reduced inhibitory activity towards the L38L↑N↑L PR in comparison with subtype C-SA HIV-1 PR. This observation suggests that the insertion and mutations significantly affect the binding affinities or characteristics of the HIV PIs and/or parent PR. The same trend for the computational binding free energies was observed for eight of the nine inhibitors with respect to the experimental binding free energies. The outcome of this study shows that ONIOM method can be used as a reliable computational approach to rationalize lead compounds against specific targets. The nature of the intermolecular interactions in terms of the host-guest hydrogen bond interactions is discussed using the atoms in molecules (AIM) analysis. Natural bond orbital analysis was also used to determine the extent of charge transfer between the QM region of the L38L↑N↑L PR enzyme and FDA approved drugs. AIM analysis showed that the interaction between the QM region of the L38L↑N↑L PR and FDA approved drugs are electrostatic dominant, the bond stability computed from the NBO analysis supports the results from the AIM application. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to provide information that will aid in the design of much improved HIV-1 PR antiviral drugs.

Public Awareness of Uterine Power Morcellation Through US Food and Drug Administration Communications: Analysis of Google Trends Search Term Patterns.

PubMed

Wood, Lauren N; Jamnagerwalla, Juzar; Markowitz, Melissa A; Thum, D Joseph; McCarty, Philip; Medendorp, Andrew R; Raz, Shlomo; Kim, Ja-Hong

2018-04-26

Uterine power morcellation, where the uterus is shred into smaller pieces, is a widely used technique for removal of uterine specimens in patients undergoing minimally invasive abdominal hysterectomy or myomectomy. Complications related to power morcellation of uterine specimens led to US Food and Drug Administration (FDA) communications in 2014 ultimately recommending against the use of power morcellation for women undergoing minimally invasive hysterectomy. Subsequently, practitioners drastically decreased the use of morcellation. We aimed to determine the effect of increased patient awareness on the decrease in use of the morcellator. Google Trends is a public tool that provides data on temporal patterns of search terms, and we correlated this data with the timing of the FDA communication. Weekly relative search volume (RSV) was obtained from Google Trends using the term “morcellation.” Higher RSV corresponds to increases in weekly search volume. Search volumes were divided into 3 groups: the 2 years prior to the FDA communication, a 1-year period following, and thereafter, with the distribution of the weekly RSV over the 3 periods tested using 1-way analysis of variance. Additionally, we analyzed the total number of websites containing the term “morcellation” over this time. The mean RSV prior to the FDA communication was 12.0 (SD 15.8), with the RSV being 60.3 (SD 24.7) in the 1-year after and 19.3 (SD 5.2) thereafter (P<.001). The mean number of webpages containing the term “morcellation” in 2011 was 10,800, rising to 18,800 during 2014 and 36,200 in 2017. Google search activity about morcellation of uterine specimens increased significantly after the FDA communications. This trend indicates an increased public awareness regarding morcellation and its complications. More extensive preoperative counseling and alteration of surgical technique and clinician practice may be necessary. ©Lauren N Wood, Juzar Jamnagerwalla, Melissa A Markowitz, D Joseph Thum, Philip McCarty, Andrew R Medendorp, Shlomo Raz, Ja-Hong Kim. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 26.04.2018.

75 FR 29561 - Memorandum of Understanding Between the Food and Drug Administration and Drugs.Com

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0004] [FDA 225-09-0012] Memorandum of Understanding Between the Food and Drug Administration and Drugs.Com... Administration (FDA) is providing notice of a memorandum of understanding (MOU) between FDA and Drugs.Com. The...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false The Food and Drug Administration's (FDA's... (CONTINUED) FOOD ADDITIVES Premarket Notifications § 170.105 The Food and Drug Administration's (FDA's... data or other information available to FDA, including data not submitted by the manufacturer or...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

77 FR 55845 - Science Board to the Food and Drug Administration: Request for Nominations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001... Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is requesting nominations to serve on the Science Board to FDA (Science Board). FDA seeks to include the views of women and men...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

76 FR 62073 - Guidance for Industry on Implementation of the Fee Provisions of the FDA Food Safety...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0721] Guidance for Industry on Implementation of the Fee Provisions of the FDA Food Safety Modernization Act... Administration (FDA) is announcing the availability of a guidance for industry entitled ``Implementation of the...

21 CFR 314.105 - Approval of an application and an abbreviated application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA...) FDA will approve an application and issue the applicant an approval letter on the basis of draft... labeling changes exactly as directed, and upon the applicant submitting to FDA a copy of the final printed...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 314.160 - Approval of an application or abbreviated application for which approval was previously refused...

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... of an applicant, FDA may, on the basis of new data, approve an application or abbreviated application which it had previously refused, suspended, or withdrawn approval. FDA will publish a notice in the...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 1271.27 - Will FDA assign me a registration number?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Will FDA assign me a registration number? 1271.27..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA assign me a registration number? (a) FDA will assign each location a permanent registration number. (b...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 170.105 - The Food and Drug Administration's (FDA's) determination that a premarket notification for a food...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false The Food and Drug Administration's (FDA's... and Drug Administration's (FDA's) determination that a premarket notification for a food contact substance (FCN) is no longer effective. (a) If data or other information available to FDA, including data...

21 CFR 516.34 - FDA recognition of exclusive marketing rights.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false FDA recognition of exclusive marketing rights. 516... SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive marketing rights. (a) FDA will send the sponsor (or the permanent-resident U.S. agent, if applicable) timely...

21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... application. (a) FDA will refuse to approve an abbreviated application for a new drug under section 505(j) of... FDA with respect to the active ingredient, route of administration, dosage form, or strength that is...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 314.162 - Removal of a drug product from the list.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.162 Removal of a drug product from the list. (a) FDA will remove a... that the withdrawal from the market has ceased or is not for safety or effectiveness reasons. (b) FDA...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

21 CFR 806.30 - FDA access to records.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false FDA access to records. 806.30 Section 806.30 Food... DEVICES MEDICAL DEVICES; REPORTS OF CORRECTIONS AND REMOVALS Reports and Records § 806.30 FDA access to... designated by FDA and under section 704(e) of the act, permit such officer or employee at all reasonable...

78 FR 5463 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... currently assessing any additional data requirements. In this regard, FDA published an Advance Notice of... report. Here, e-form FDA 3744a and reporting via the Electronic Submission Gateway are provided by FDA... January 17, 2012 (77 FR 2302), FDA published a 60-day notice requesting public comment on the proposed...

Drugs and Alcohol in Civil Aviation Accident Pilot Fatalities from 2004-2008

DTIC Science & Technology

2011-09-01

Quinine 16 0.9 19 1.1 37 2.3 42 3.1 FDA 򒾅 Salicylatesβ 96 5.2 114 6.8 41 2.6 11 0.8 FDA 򒾅 Simethicone 0 0.0 0 0.0 0 0.0 1 0.1 FDA 1996... Simethicone 0 0.0 0 0.0 0 0.0 1 0.1 FDA 1996 Triprolidine 0 0.0 0 0.0 2 0.1 2 0.1 FDA 򒾅 β – Screening Cutoff Increased in 2002 μ - Public Law

Removal of Review and Reclassification Procedures for Biological Products Licensed Prior to July 1, 1972. Final rule.

PubMed

2016-02-12

The Food and Drug Administration (FDA, the Agency, or we) is removing two regulations that prescribe procedures for FDA's review and classification of biological products licensed before July 1, 1972. FDA is taking this action because the two regulations are obsolete and no longer necessary in light of other statutory and regulatory authorities established since 1972, which allow FDA to evaluate and monitor the safety and effectiveness of all biological products. In addition, other statutory and regulatory authorities authorize FDA to revoke a license for biological products because they are not safe and effective, or are misbranded. FDA is taking this action as part of its retrospective review of its regulations to promote improvement and innovation.

Selecting risk factors: a comparison of discriminant analysis, logistic regression and Cox's regression model using data from the Tromsø Heart Study.

PubMed

Brenn, T; Arnesen, E

1985-01-01

For comparative evaluation, discriminant analysis, logistic regression and Cox's model were used to select risk factors for total and coronary deaths among 6595 men aged 20-49 followed for 9 years. Groups with mortality between 5 and 93 per 1000 were considered. Discriminant analysis selected variable sets only marginally different from the logistic and Cox methods which always selected the same sets. A time-saving option, offered for both the logistic and Cox selection, showed no advantage compared with discriminant analysis. Analysing more than 3800 subjects, the logistic and Cox methods consumed, respectively, 80 and 10 times more computer time than discriminant analysis. When including the same set of variables in non-stepwise analyses, all methods estimated coefficients that in most cases were almost identical. In conclusion, discriminant analysis is advocated for preliminary or stepwise analysis, otherwise Cox's method should be used.

The Tip of the Iceberg of Misleading Online Advertising Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

PubMed

Mintzes, Barbara

2016-02-18

Kim's overview of Food and Drug Administration (FDA) regulatory actions from 2005 to 2014 is a comprehensive analysis of the US regulatory experience with online direct-to-consumer advertising (DTCA) of prescription medicines. This experience is of relevance internationally as online DTCA reaches the English-speaking public globally, despite the illegality of DTCA in most countries. The most common violations were omissions or minimizations of risk information, overstatements of efficacy, unsubstantiated claims, and promotion of unapproved ("off-label") use. Nearly one fourth of violations involved cancer drugs, raising additional concerns about patient vulnerability, limited treatment advance, and high costs. Based on content analyses of online DTCA, these cases likely reflect a small proportion of unbalanced and misleading promotional information available on the web. The FDA is only able to review a small proportion of promotional materials submitted to them, due to limited staffing, and the delay between first posting and regulatory action means that many people may be exposed to messages that are found to be inaccurate and misleading. The sheer volume of online DTCA, combined with the ability for content to shift continually, poses unique regulatory challenges. © 2016 by Kerman University of Medical Sciences.

Ocular toxicities associated with targeted anticancer agents: an analysis of clinical data with management suggestions

PubMed Central

Fu, Chen; Gombos, Dan S; Lee, Jared; George, Goldy C; Hess, Kenneth; Whyte, Andrew; Hong, David S

2017-01-01

Ocular toxicities are among the most common adverse events resulting from targeted anticancer agents and are becoming increasingly relevant in the management of patients on these agents. The purpose of this study is to provide a framework for management of these challenging toxicities based on objective data from FDA labels and from analysis of the literature. All oncologic drugs approved by the FDA up to March 14, 2015, were screened for inclusion. A total of 16 drugs (12 small-molecule drugs and 4 monoclonal antibodies) were analyzed for ocular toxicity profiles based on evidence of ocular toxicity. Trials cited by FDA labels were retrieved, and a combination search in Medline, Google Scholar, the Cochrane database, and the NIH Clinical Trials Database was conducted. The majority of ocular toxicities reported were low severity, and the most common were conjunctivitis and “visual disturbances.” However, severe events including incidents of blindness, retinal vascular occlusion, and corneal ulceration occurred. The frequency and severity at which ocular toxicities occur merits a more multidisciplinary approach to managing patients with agents that are known to cause ocular issues. We suggest a standardized methodology for referral and surveillance of patients who are potentially at risk of severe ocular toxicity. PMID:28938590

A single-laboratory validated method for the generation of DNA barcodes for the identification of fish for regulatory compliance.

PubMed

Handy, Sara M; Deeds, Jonathan R; Ivanova, Natalia V; Hebert, Paul D N; Hanner, Robert H; Ormos, Andrea; Weigt, Lee A; Moore, Michelle M; Yancy, Haile F

2011-01-01

The U.S. Food and Drug Administration is responsible for ensuring that the nation's food supply is safe and accurately labeled. This task is particularly challenging in the case of seafood where a large variety of species are marketed, most of this commodity is imported, and processed product is difficult to identify using traditional morphological methods. Reliable species identification is critical for both foodborne illness investigations and for prevention of deceptive practices, such as those where species are intentionally mislabeled to circumvent import restrictions or for resale as species of higher value. New methods that allow accurate and rapid species identifications are needed, but any new methods to be used for regulatory compliance must be both standardized and adequately validated. "DNA barcoding" is a process by which species discriminations are achieved through the use of short, standardized gene fragments. For animals, a fragment (655 base pairs starting near the 5' end) of the cytochrome c oxidase subunit 1 mitochondrial gene has been shown to provide reliable species level discrimination in most cases. We provide here a protocol with single-laboratory validation for the generation of DNA barcodes suitable for the identification of seafood products, specifically fish, in a manner that is suitable for FDA regulatory use.

Science/Society Case Study

ERIC Educational Resources Information Center

Moore, John W., Ed.; Moore, Elizabeth A., Ed.

1977-01-01

Discusses the role of the US Food and Drug Administration (FDA) in protecting the American public from carcinogens. Describes scientific testing methodology, risk-benefit analysis and the Delaney clause with its application to saccharin. (CP)

OpenFDA: an innovative platform providing access to a wealth of FDA’s publicly available data

PubMed Central

Kass-Hout, Taha A; Mohebbi, Matthew; Nelsen, Hans; Baker, Adam; Levine, Jonathan; Johanson, Elaine; Bright, Roselie A

2016-01-01

Objective The objective of openFDA is to facilitate access and use of big important Food and Drug Administration public datasets by developers, researchers, and the public through harmonization of data across disparate FDA datasets provided via application programming interfaces (APIs). Materials and Methods Using cutting-edge technologies deployed on FDA’s new public cloud computing infrastructure, openFDA provides open data for easier, faster (over 300 requests per second per process), and better access to FDA datasets; open source code and documentation shared on GitHub for open community contributions of examples, apps and ideas; and infrastructure that can be adopted for other public health big data challenges. Results Since its launch on June 2, 2014, openFDA has developed four APIs for drug and device adverse events, recall information for all FDA-regulated products, and drug labeling. There have been more than 20 million API calls (more than half from outside the United States), 6000 registered users, 20,000 connected Internet Protocol addresses, and dozens of new software (mobile or web) apps developed. A case study demonstrates a use of openFDA data to understand an apparent association of a drug with an adverse event. Conclusion With easier and faster access to these datasets, consumers worldwide can learn more about FDA-regulated products. PMID:26644398

78 FR 65334 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-31

... information, including certain labeling information, to FDA for approval to market a product in interstate... and in a form that FDA can process, review, and archive. This requirement is in addition to the....12(b) in table 1 of this document. In July 1997, FDA revised Form FDA 356h ``Application to Market a...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... virus, Type 1 (e.g., FDA licensed screening test for anti-HIV-1); (2) Human immunodeficiency virus, Type 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

21 CFR 1.392 - Who receives a copy of the detention order?

Code of Federal Regulations, 2013 CFR

2013-04-01

... Fda Order A Detention? § 1.392 Who receives a copy of the detention order? (a) FDA must issue the... place where the article is detained, FDA must provide a copy of the detention order to the owner of the article of food if the owner's identity can be determined readily. (b) If FDA issues a detention order for...

21 CFR 1.392 - Who receives a copy of the detention order?

Code of Federal Regulations, 2012 CFR

2012-04-01

... Fda Order A Detention? § 1.392 Who receives a copy of the detention order? (a) FDA must issue the... place where the article is detained, FDA must provide a copy of the detention order to the owner of the article of food if the owner's identity can be determined readily. (b) If FDA issues a detention order for...

21 CFR 111.610 - What records must be made available to FDA?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false What records must be made available to FDA? 111... records must be made available to FDA? (a) You must have all records required under this part, or copies of such records, readily available during the retention period for inspection and copying by FDA when...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2014 CFR

2014-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...

21 CFR 1.378 - What criteria does FDA use to order a detention?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false What criteria does FDA use to order a detention? 1... General Provisions § 1.378 What criteria does FDA use to order a detention? An officer or qualified employee of FDA may order the detention of any article of food that is found during an inspection...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 1.392 - Who receives a copy of the detention order?

Code of Federal Regulations, 2011 CFR

2011-04-01

... Fda Order A Detention? § 1.392 Who receives a copy of the detention order? (a) FDA must issue the... place where the article is detained, FDA must provide a copy of the detention order to the owner of the article of food if the owner's identity can be determined readily. (b) If FDA issues a detention order for...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 1.378 - What criteria does FDA use to order a detention?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false What criteria does FDA use to order a detention? 1... General Provisions § 1.378 What criteria does FDA use to order a detention? An officer or qualified employee of FDA may order the detention of any article of food that is found during an inspection...

21 CFR 111.610 - What records must be made available to FDA?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What records must be made available to FDA? 111... records must be made available to FDA? (a) You must have all records required under this part, or copies of such records, readily available during the retention period for inspection and copying by FDA when...

21 CFR 1.378 - What criteria does FDA use to order a detention?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false What criteria does FDA use to order a detention? 1... General Provisions § 1.378 What criteria does FDA use to order a detention? An officer or qualified employee of FDA may order the detention of any article of food that is found during an inspection...

21 CFR 111.610 - What records must be made available to FDA?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false What records must be made available to FDA? 111... records must be made available to FDA? (a) You must have all records required under this part, or copies of such records, readily available during the retention period for inspection and copying by FDA when...

21 CFR 1.378 - What criteria does FDA use to order a detention?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What criteria does FDA use to order a detention? 1... General Provisions § 1.378 What criteria does FDA use to order a detention? An officer or qualified employee of FDA may order the detention of any article of food that is found during an inspection...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false How does FDA define the terms used in this part... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.3 How does FDA..., for an estimated period of time. FDA, we, or us means the Food and Drug Administration. Five-day...

21 CFR 111.610 - What records must be made available to FDA?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 2 2012-04-01 2012-04-01 false What records must be made available to FDA? 111... records must be made available to FDA? (a) You must have all records required under this part, or copies of such records, readily available during the retention period for inspection and copying by FDA when...

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false How does FDA define the terms used in this part... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.3 How does FDA..., for an estimated period of time. FDA, we, or us means the Food and Drug Administration. Five-day...

21 CFR 1.378 - What criteria does FDA use to order a detention?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false What criteria does FDA use to order a detention? 1... General Provisions § 1.378 What criteria does FDA use to order a detention? An officer or qualified employee of FDA may order the detention of any article of food that is found during an inspection...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2011 CFR

2011-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 314.72 - Change in ownership of an application.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.72... required to be kept under § 314.81, or a request for a copy of the application from FDA's files. FDA will provide a copy of the application to the new owner under the fee schedule in § 20.45 of FDA's public...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2012 CFR

2012-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false How does FDA define the terms used in this part... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.3 How does FDA..., for an estimated period of time. FDA, we, or us means the Food and Drug Administration. Five-day...

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false How does FDA define the terms used in this part... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.3 How does FDA..., for an estimated period of time. FDA, we, or us means the Food and Drug Administration. Five-day...

21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

Code of Federal Regulations, 2013 CFR

2013-04-01

... initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... Human Prescription Drugs § 14.171 Utilization of an advisory committee on the initiative of FDA. (a) Any... monitoring of the matter and consultation with FDA on behalf of the committee. The member or consultant may...

21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false How will FDA handle classified information in an... Animal Consumption What Is the Appeal Process for A Detention Order? § 1.406 How will FDA handle... disclosure in the interest of national security (“classified information”), FDA will not provide you with...

21 CFR 111.610 - What records must be made available to FDA?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 2 2013-04-01 2013-04-01 false What records must be made available to FDA? 111... records must be made available to FDA? (a) You must have all records required under this part, or copies of such records, readily available during the retention period for inspection and copying by FDA when...

21 CFR 1.392 - Who receives a copy of the detention order?

Code of Federal Regulations, 2010 CFR

2010-04-01

... Fda Order A Detention? § 1.392 Who receives a copy of the detention order? (a) FDA must issue the... place where the article is detained, FDA must provide a copy of the detention order to the owner of the article of food if the owner's identity can be determined readily. (b) If FDA issues a detention order for...

[Discrimination of Rice Syrup Adulterant of Acacia Honey Based Using Near-Infrared Spectroscopy].

PubMed

Zhang, Yan-nan; Chen, Lan-zhen; Xue, Xiao-feng; Wu, Li-ming; Li, Yi; Yang, Juan

2015-09-01

At present, the rice syrup as a low price of the sweeteners was often adulterated into acacia honey and the adulterated honeys were sold in honey markets, while there is no suitable and fast method to identify honey adulterated with rice syrup. In this study, Near infrared spectroscopy (NIR) combined with chemometric methods were used to discriminate authenticity of honey. 20 unprocessed acacia honey samples from the different honey producing areas, mixed? with different proportion of rice syrup, were prepared of seven different concentration gradient? including 121 samples. The near infrared spectrum (NIR) instrument and spectrum processing software have been applied in the? spectrum? scanning and data conversion on adulterant samples, respectively. Then it was analyzed by Principal component analysis (PCA) and canonical discriminant analysis methods in order to discriminating adulterated honey. The results showed that after principal components analysis, the first two principal components accounted for 97.23% of total variation, but the regionalism of the score plot of the first two PCs was not obvious, so the canonical discriminant analysis was used to make the further discrimination, all samples had been discriminated correctly, the first two discriminant functions accounted for 91.6% among the six canonical discriminant functions, Then the different concentration of adulterant samples can be discriminated correctly, it illustrate that canonical discriminant analysis method combined with NIR spectroscopy is not only feasible but also practical for rapid and effective discriminate of the rice syrup adulterant of acacia honey.

Risk management policy and black-box warnings: a qualitative analysis of US FDA proceedings.

PubMed

Cook, Daniel M; Gurugubelli, Rama K; Bero, Lisa A

2009-01-01

The US FDA increasingly applies risk management to drug safety policy. Little is known about the process by which the FDA approves labelling changes. Although advisory committees can recommend any of the risk management tools, including the use of 'black-box warnings', it is unknown whether they deliberate on these questions or how they apply the principles of risk minimization or management during their considerations of drug licensing. To examine the process by which risk management is considered by the FDA, including the role of FDA advisory committees. We also aimed to identify and describe drug labelling changes and additions, including the prevalence of black-box warnings. We electronically obtained publicly available information regarding drug approvals, drug revisions and advisory committee meetings over 3 years (2004-6) from the FDA. Data in the form of meeting transcripts and full histories of labelling changes were collected on drugs discussed by advisory committees. We then searched and qualitatively analysed the meeting transcripts to identify themes in the discussion. We also created a database of all prescription drug labelling changes for 3 years and examined which drugs have had the most changes. We describe the risk management consideration process and report the frequency and characteristics of labelling changes. Excerpts from the transcripts are selected to illustrate both typical and atypical features of the discussion. A total of 174 black-box changes were made in the 3-year period of our study, of which 77 were new black-box warnings and 97 were revisions in black-box warnings. Of 77 new black-box warning additions, only 11 drugs were discussed by the advisory committees. Of the 17 most frequently revised drug labels in these 3 years, two were discussed in the advisory committee meetings. Advisory meeting discussions revealed confusion about black-box warnings and emphasized potential consequences of the warnings rather than their content. The safety labelling of drugs on the market is changed often. Panels of advisors consider only a few drugs, rarely discuss the labelling requirements, and display confusion about applying black-box warnings. The creation and application of black-box warnings on prescription medications should receive closer attention from the FDA and its advisors.

Impact of the 2011 FDA transvaginal mesh safety update on AUGS members' use of synthetic mesh and biologic grafts in pelvic reconstructive surgery.

PubMed

Clemons, Jeffrey L; Weinstein, Milena; Guess, Marsha K; Alperin, Marianna; Moalli, Pamela; Gregory, William Thomas; Lukacz, Emily S; Sung, Vivian W; Chen, Bertha H; Bradley, Catherine S

2013-01-01

To describe the frequency of use and recent change in use of synthetic mesh and biologic grafts in pelvic organ prolapse (POP) and stress urinary incontinence surgery by American Urogynecology Society (AUGS) members. An electronic survey of AUGS members was conducted between December 2011 and January 2012. Frequency of graft use in POP (overall and by transvaginal and transabdominal approaches) and stress urinary incontinence surgery was queried relative to the timing of the 2011 Food and Drug Administration (FDA) safety update. Rates of materials' use before and after the statement were compared using Wilcoxon signed rank test. Fifty-three percent (507/962) of AUGS members responded and were included in analysis; 79% were urogynecologists. Before the FDA warning, in POP surgery, most (90%) used synthetic mesh and fewer (34%) used biologic grafts; 99% used synthetic mesh slings. After the FDA statement, respondents reported an overall decrease in the percent of POP cases in which they used synthetic mesh (P < 0.001) but no change in biologic graft use for POP (P = 0.37) or synthetic mesh sling use (P = 0.10). Specifically, transvaginal mesh use decreased: 40% reported decreased use and 12% stopped use. However, transvaginal mesh was still used by 61% of respondents in at least some cases. No change (62%) or increased use (12%) of mesh was reported for transabdominal POP procedures. Synthetic mesh use in transvaginal POP surgery decreased after the 2011 FDA safety update, but synthetic mesh use for transabdominal POP repair and sling procedures and overall biologic graft use in POP surgery did not decrease.

Regulatory withdrawal of medicines marketed with uncertain benefits: the bevacizumab case study.

PubMed

Vitry, Agnes; Nguyen, Tuan; Entwistle, Vikky; Roughead, Elizabeth

2015-01-01

Withdrawal of conditional regulatory approval or subsidization of new medicines when subsequent evidence does not confirm early trial results may not be well understood or accepted by the public. We present a case study of the US Food and Drug Administration (FDA)'s decision to withdraw the indication of bevacizumab for the treatment of advanced breast cancer and include an analysis of the reactions of stakeholders with a view to identifying opportunities for improving risk management for new medicines with conditional approval or funding. We drew on a range of information sources, including FDA documents, medical journals and media reports, to describe the evidentiary basis of the FDA decisions. We analysed the reactions and perspectives of the stakeholders. In 2008 bevacizumab was granted conditional approval for treatment of advanced breast cancer by the FDA pending submission of supplementary satisfactory evidence. In 2011 the FDA decision to withdraw the indication was met with a hostile reaction from many clinicians and cancer survivors. There were different interpretations of the therapeutic value of bevacizumab with strong beliefs among cancer survivors that the medicine was effective and potential harm was manageable. High expectations of the public may have been encouraged by overly positive media reports and limited understanding by the public of the complexity of the scientific evaluation of new medicines and of the regulatory processes. Improving understanding and acceptance of approval or coverage schemes conditional to evidence development may require the development of risk management plans by regulatory and funding institutions. They may include a range of strategies such as requirements for formal patient acknowledgment of the conditional availability of the medicine, 'black-triangle' equivalent labels that identify full approval is based on pending evidence, and ongoing communication with the media, public and health professionals.

Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters.

PubMed

Kim, Hyosun

2015-08-25

For the purpose of understanding the Food and Drug Administration's (FDA's) concerns regarding online promotion of prescription drugs advertised directly to consumers, this study examines notices of violations (NOVs) and warning letters issued by the FDA to pharmaceutical manufacturers. The FDA's warning letters and NOVs, which were issued to pharmaceutical companies over a 10-year period (2005 to 2014) regarding online promotional activities, were content-analyzed. Six violation categories were identified: risk information, efficacy information, indication information, product labeling, material information issues, and approval issues. The results reveal that approximately 95% of the alleged violations were found on branded drug websites, in online paid advertisements, and in online videos. Of the total 179 violations, the majority of the alleged violations were concerned with the lack of risk information and/or misrepresentation of efficacy information, suggesting that achieving a fair balance of benefit versus risk information is a major problem with regard to the direct-to-consumer advertising (DTCA) of prescription drugs. In addition, the character space limitations of online platforms, eg, sponsored links on search engines, pose challenges for pharmaceutical marketers with regard to adequately communicating important drug information, such as indication information, risk information, and product labeling. Presenting drug information in a fair and balanced manner remains a major problem. Industry guidance should consider addressing visibility and accessibility of information in the web environment to help pharmaceutical marketers meet the requirements for direct-to-consumer promotion and to protect consumers from misleading drug information. Promotion via social media warrants further attention, as pharmaceutical manufacturers have already begun actively establishing a social media presence, and the FDA has thus begun to keep tabs on social media promotions of prescription drugs. © 2015 by Kerman University of Medical Sciences.

Estimating the extent of reporting to FDA: a case study of statin-associated rhabdomyolysis.

PubMed

McAdams, Mara; Staffa, Judy; Dal Pan, Gerald

2008-03-01

To estimate the extent of reporting to FDA through statin-associated rhabdomyolysis data. Data included incidence rates (IRs) of hospitalized rhabdomyolysis among statin users from a population-based study, and comparable reported AERS cases and national estimates of statin use from an AERS analysis. Using IRs, national estimates of statin use and average days supply per prescription, we estimated the number of US statin-associated cases of hospitalized rhabdomyolysis. We compared this estimate to the observed number of cases reported to FDA to evaluate the extent of reporting. We repeated this method for atorvastatin, cerivastatin, pravastatin, and simvastatin and statin combinations. We performed sensitivity analyses to check for biases such as misclassification of statin use and cohort selection bias. We evaluated potential time-dependent cerivastatin reporting by a "Dear Health Care Provider (DHCP)" letter. The estimated extent of reporting to FDA varied by statin (atorvastatin, 5.0%; cerivastatin, 31.2%; simvastatin, 14.2%; all four combined, 17.7%; and non-cerivastatin statins combined, 9.9%). No pravastatin-associated cohort cases occurred. Across a reasonable value range, sensitivity analyses did not significantly alter the results; overall the cohort was similar to national statin-users. There was a large increase in AERS reports after the cerivastatin DHCP letter and the estimated extent of reporting increased from 14.8 to 35.0%. The extent of reporting of adverse events to FDA varied by statin and may be influenced by publicity. For statins-associated rhabdomyolysis, the estimated extent of reporting appears to range from 5 to 30% but in the absence of stimulated reporting appears to be 5-15%. Copyright 2008 John Wiley & Sons, Ltd.

The Role of Adverse Event Reporting in the FDA Response to a Multistate Outbreak of Liver Disease Associated with a Dietary Supplement

PubMed Central

DeBeck, Heidi J.; LeBlanc, Pamela; Mogen, Kathryn M.; Wolpert, Beverly J.; Sabo, Jonathan L.; Salter, Monique; Seelman, Sharon L.; Lance, Susan E.; Monahan, Caitlin; Steigman, David S.; Gensheimer, Kathleen

2015-01-01

Objective Liver disease is a potential complication from using dietary supplements. This study investigated an outbreak of non-viral liver disease associated with the use of OxyELITE ProTM, a dietary supplement used for weight loss and/or muscle building. Methods Illness details were ascertained from MedWatch reports submitted to the U.S. Food and Drug Administration (FDA) describing consumers who ingested OxyELITE Pro alone or in combination with other dietary supplements. FDA's Forensic Chemistry Center analyzed samples of OxyELITE Pro. Results From February 2012 to February 2014, FDA received 114 reports of adverse events of all kinds involving consumers who ingested OxyELITE Pro. The onset of illness for the first report was December 2010 and for the last report was January 2014. Thirty-three states, two foreign nations, and Puerto Rico submitted reports. Fifty-five of the reports (48%) described liver disease in the absence of viral infection, gallbladder disease, autoimmune disease, or other known causes of liver damage. A total of 33 (60%) of these patients were hospitalized, and three underwent liver transplantation. In early 2013, OxyELITE Pro products entered the market with a formulation distinct from products sold previously. The new formulation replaced 1,3-dimethylamylamine with aegeline. However, the manufacturer failed to submit to FDA a required “new dietary ingredient” notice for the use of aegeline in OxyELITE Pro products. Laboratory analysis identified no drugs, poisons, pharmaceuticals, toxic metals, usnic acid, N-Nitroso-fenfluramine, pyrrolizidine alkaloids, aristocholic acid, or phenethylamines in the products. Conclusions Vigilant surveillance is required for adverse events linked to the use of dietary supplements. PMID:26327730

Clinical Evidence Supporting US Food and Drug Administration Approval of Otolaryngologic Prescription Drug Indications, 2005-2014.

PubMed

Rathi, Vinay K; Wang, Bo; Ross, Joseph S; Downing, Nicholas S; Kesselheim, Aaron S; Gray, Stacey T

2017-04-01

Objective The US Food and Drug Administration (FDA) approves indications for prescription drugs based on premarket pivotal clinical studies designed to demonstrate safety and efficacy. We characterized the pivotal studies supporting FDA approval of otolaryngologic prescription drug indications. Study Design Retrospective cross-sectional analysis. Setting Publicly available FDA documents. Subjects Recently approved (2005-2014) prescription drug indications for conditions treated by otolaryngologists or their multidisciplinary teams. Drugs could be authorized for treatment of otolaryngologic disease upon initial approval (original indications) or thereafter via supplemental applications (supplemental indications). Methods Pivotal studies were categorized by enrollment, randomization, blinding, comparator type, and primary endpoint. Results Between 2005 and 2014, the FDA approved 48 otolaryngologic prescription drug indications based on 64 pivotal studies, including 21 original indications (19 drugs, 31 studies) and 27 supplemental indications (18 drugs, 33 studies). Median enrollment was 299 patients (interquartile range, 198-613) for original indications and 197 patients (interquartile range, 64-442) for supplemental indications. Most indications were supported by ≥1 randomized study (original: 20/21 [95%], supplemental: 21/27 [78%]) and ≥1 double-blinded study (original: 14/21 [67%], supplemental: 17/27 [63%]). About half of original indications (9/21 [43%]) and one-quarter of supplemental indications (7/27 [26%]) were supported by ≥1 active-controlled study. Nearly half (original: 8/21 [38%], supplemental: 14/27 [52%]) of all indications were approved based exclusively on studies using surrogate markers as primary endpoints. Conclusion The quality of clinical evidence supporting FDA approval of otolaryngologic prescription drug indications varied widely. Otolaryngologists should consider limitations in premarket evidence when helping patients make informed treatment decisions about newly approved drugs.

Medicare covers the majority of FDA-approved devices and Part B drugs, but restrictions and discrepancies remain.

PubMed

Chambers, James D; May, Katherine E; Neumann, Peter J

2013-06-01

The Food and Drug Administration (FDA) and Medicare use different standards to determine, first, whether a new drug or medical device can be marketed to the public and, second, if the federal health insurance program will pay for use of the drug or device. This discrepancy creates hurdles and uncertainty for drug and device manufacturers. We analyzed discrepancies between FDA approval and Medicare national coverage determinations for sixty-nine devices and Part B drugs approved during 1999-2011. We found that Medicare covered FDA-approved drugs or devices 80 percent of the time. However, Medicare often added conditions beyond FDA approval, particularly for devices and most often restricting coverage to patients with the most severe disease. In some instances, Medicare was less restrictive than the FDA. Our findings highlight the importance for drug and device makers of anticipating Medicare's needs when conducting clinical studies to support their products. Our findings also provide important insights for the FDA's and Medicare's pilot parallel review program.

Interview with Janet Woodcock: progress on the FDA's critical path initiative.

PubMed

Woodcock, Janet

2009-12-01

Janet Woodcock is the Director of the US FDA's Center for Drug Evaluation and Research. Dr Woodcock has held various positions within the FDA's Office of the Commissioner from October 2003 until 1 April, 2008, as Deputy Commissioner and Chief Medical Officer, Deputy Commissioner for Operations and Chief Operating Officer and Director of the Critical Path Programs. She oversaw scientific and medical regulatory operations for the FDA. Dr Woodcock served as Director of the Center for Drug Evaluation and Research at the FDA from 1994 to 2005. She previously served in other positions at the FDA including Director of the Office of Therapeutics Research and Review and Acting Deputy Director of the Center for Biologics Evaluation and Research. Dr Woodcock received her MD from Northwestern Medical School (IL, USA), and completed further training and held teaching appointments at the Pennsylvania State University (PA, USA)and the University of California in San Francisco (CA, USA). She joined the FDA in 1986.

Primaquine in vivax malaria: an update and review on management issues

PubMed Central

2011-01-01

Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs. PMID:22152065

Primaquine in vivax malaria: an update and review on management issues.

PubMed

Fernando, Deepika; Rodrigo, Chaturaka; Rajapakse, Senaka

2011-12-12

Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs.

8th GCC: consolidated feedback to US FDA on the 2013 draft FDA guidance on bioanalytical method validation.

PubMed

Bower, Joseph; Fast, Douglas; Garofolo, Fabio; Gouty, Dominique; Hayes, Roger; Lowes, Steve; Nicholson, Robert; LeLacheur, Richard; Bravo, Jennifer; Shoup, Ronald; Dumont, Isabelle; Carbone, Mary; Zimmer, Jennifer; Ortuno, Jordi; Caturla, Maria Cruz; Datin, Jim; Lansing, Tim; Fatmi, Saadya; Struwe, Petra; Sheldon, Curtis; Islam, Rafiqul; Yu, Mathilde; Hulse, Jim; Kamerud, John; Lin, John; Doughty, John; Kurylak, Kai; Tang, Daniel; Buonarati, Mike; Blanchette, Alexandre; Levesque, Ann; Gagnon-Carignan, Sofi; Lin, Jenny; Ray, Gene; Liu, Yanseng; Khan, Masood; Xu, Allan; El-Sulayman, Gibran; DiMarco, Chantal; Bouhajib, Mohammed; Tacey, Dick; Jenkins, Rand; der Strate, Barry van; Briscoe, Chad; Karnik, Shane; Rhyne, Paul; Garofolo, Wei; Schultz, Gary; Roberts, Andrew; Redrup, Mike; DuBey, Ira; Conliffe, Phyllis; Pekol, Teri; Hantash, Jamil; Cojocaru, Laura; Allen, Mike; Reuschel, Scott; Watson, Andrea; Farrell, Colin; Groeber, Elizabeth; Malone, Michele; Nowatzke, William; Fang, Xinping

2014-01-01

The 8th GCC Closed Forum for Bioanalysis was held in Baltimore, MD, USA on 5 December 2013, immediately following the 2013 AAPS Workshop (Crystal City V): Quantitative Bioanalytical Methods Validation and Implementation--The 2013 Revised FDA Guidance. This GCC meeting was organized to discuss the contents of the draft revised FDA Guidance on bioanalytical method validation that was published in September 2013 and consolidate the feedback of the GCC members. In attendance were 63 senior-level participants, from seven countries, representing 46 bioanalytical CRO companies/sites. This event represented a unique opportunity for CRO bioanalytical experts to share their opinions and concerns regarding the draft FDA Guidance, and to build unified comments to be provided to the FDA.

Determining the non-inferiority margin for patient reported outcomes.

PubMed

Gerlinger, Christoph; Schmelter, Thomas

2011-01-01

One of the cornerstones of any non-inferiority trial is the choice of the non-inferiority margin delta. This threshold of clinical relevance is very difficult to determine, and in practice, delta is often "negotiated" between the sponsor of the trial and the regulatory agencies. However, for patient reported, or more precisely patient observed outcomes, the patients' minimal clinically important difference (MCID) can be determined empirically by relating the treatment effect, for example, a change on a 100-mm visual analogue scale, to the patient's satisfaction with the change. This MCID can then be used to define delta. We used an anchor-based approach with non-parametric discriminant analysis and ROC analysis and a distribution-based approach with Norman's half standard deviation rule to determine delta in three examples endometriosis-related pelvic pain measured on a 100-mm visual analogue scale, facial acne measured by lesion counts, and hot flush counts. For each of these examples, all three methods yielded quite similar results. In two of the cases, the empirically derived MCIDs were smaller or similar of deltas used before in non-inferiority trials, and in the third case, the empirically derived MCID was used to derive a responder definition that was accepted by the FDA. In conclusion, for patient-observed endpoints, the delta can be derived empirically. In our view, this is a better approach than that of asking the clinician for a "nice round number" for delta, such as 10, 50%, π, e, or i. Copyright © 2011 John Wiley & Sons, Ltd.

75 FR 40839 - Agency Information Collection Activities; Proposed Collection; Comment Request; Hazard Analysis...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-14

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0357] Agency Information Collection Activities; Proposed Collection; Comment Request; Hazard Analysis and Critical Control Point Procedures for the Safe and Sanitary Processing and Importing of Juice AGENCY: Food...

Cost analysis of commercial pasteurization of orange juice by pulsed electric fields

USDA-ARS?s Scientific Manuscript database

The cost of pulsed electric field (PEF) pasteurization of orange juice was estimated. The cost analysis was based on processing conditions that met the US FDA (5 log reduction) requirement for fruit juice pasteurization and that achieved a 2 month microbial shelf-life. PEF-treated samples processed ...

21 CFR 1.279 - When must prior notice be submitted to FDA?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false When must prior notice be submitted to FDA? 1.279... Imported Food § 1.279 When must prior notice be submitted to FDA? (a) Except as provided in paragraph (c) of this section, you must submit the prior notice to FDA and the prior notice submission must be...

21 CFR 1.279 - When must prior notice be submitted to FDA?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false When must prior notice be submitted to FDA? 1.279... Imported Food § 1.279 When must prior notice be submitted to FDA? (a) Except as provided in paragraph (c) of this section, you must submit the prior notice to FDA and the prior notice submission must be...

21 CFR 1.279 - When must prior notice be submitted to FDA?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false When must prior notice be submitted to FDA? 1.279... Imported Food § 1.279 When must prior notice be submitted to FDA? (a) Except as provided in paragraph (c) of this section, you must submit the prior notice to FDA and the prior notice submission must be...

21 CFR 1.279 - When must prior notice be submitted to FDA?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false When must prior notice be submitted to FDA? 1.279... Imported Food § 1.279 When must prior notice be submitted to FDA? (a) Except as provided in paragraph (c) of this section, you must submit the prior notice to FDA and the prior notice submission must be...

21 CFR 1.279 - When must prior notice be submitted to FDA?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false When must prior notice be submitted to FDA? 1.279... Imported Food § 1.279 When must prior notice be submitted to FDA? (a) Except as provided in paragraph (c) of this section, you must submit the prior notice to FDA and the prior notice submission must be...

21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 2 (e.g., FDA licensed screening test for anti-HIV-2); (3) Hepatitis B (e.g., FDA licensed screening test for HBsAg); and (4) Hepatitis C (e.g., FDA licensed screening test for anti-HCV). (b) In the case... been tested and found negative using FDA licensed screening tests for HIV-1, HIV-2, hepatitis B, and...

Accounting for heterogeneous treatment effects in the FDA approval process.

PubMed

Malani, Anup; Bembom, Oliver; van der Laan, Mark

2012-01-01

The FDA employs an average-patient standard when reviewing drugs: it approves a drug only if is safe and effective for the average patient in a clinical trial. It is common, however, for patients to respond differently to a drug. Therefore, the average-patient standard can reject a drug that benefits certain patient subgroups (false negatives) and even approve a drug that harms other patient subgroups (false positives). These errors increase the cost of drug development - and thus health care - by wasting research on unproductive or unapproved drugs. The reason why the FDA sticks with an average patient standard is concern about opportunism by drug companies. With enough data dredging, a drug company can always find some subgroup of patients that appears to benefit from its drug, even if the subgroup truly does not. In this paper we offer alternatives to the average patient standard that reduce the risk of false negatives without increasing false positives from drug company opportunism. These proposals combine changes to institutional design - evaluation of trial data by an independent auditor - with statistical tools to reinforce the new institutional design - specifically, to ensure the auditor is truly independent of drug companies. We illustrate our proposals by applying them to the results of a recent clinical trial of a cancer drug (motexafin gadolinium). Our analysis suggests that the FDA may have made a mistake in rejecting that drug.

The U.S. Food and Drug Administration Risk Assessment on Lead in Women’s and Children’s Vitamins Is Based on Outdated Assumptions

PubMed Central

Miodovnik, Amir; Landrigan, Philip J.

2009-01-01

Background Following a recent report of lead in certain commercial vitamin products, the U.S. Food and Drug Administration (FDA) conducted a nationwide survey to determine the Pb content in 324 multivitamin/mineral products labeled for use by women and children. The FDA compared estimated Pb exposures from each product with safe/tolerable exposure levels, termed provisional total tolerable intake (PTTI) levels, previously developed for at-risk population groups in 1992. Objective We investigated the FDA’s conclusions that Pb concentrations in all vitamin products examined do not pose a hazard to health because they are below the PTTI levels for all groups considered. Discussion For their initial estimations of PTTI levels, the FDA used a blood lead level (BLL) of 10 μg/dL as the threshold for adverse effects in children and in pregnant or lactating women. Studies have repeatedly linked chronic exposure to BLLs < 10 μg/dL with impairments in cognitive function and behavior in young children despite the absence of overt signs of toxicity. The FDA analysis also omitted any consideration of nonfood sources of Pb exposure, which is inconsistent with our current understanding of how most children develop elevated BLLs. Conclusion We feel that based on these oversights, the FDA’s conclusions are unduly reassuring and that reconsideration of their current recommendations appears warranted. PMID:19654907

The Methodology of Clinical Studies Used by the FDA for Approval of High-Risk Orthopaedic Devices.

PubMed

Barker, Jordan P; Simon, Stephen D; Dubin, Jonathan

2017-05-03

The purpose of this investigation was to examine the methodology of clinical trials used by the U.S. Food and Drug Administration (FDA) to determine the safety and effectiveness of high-risk orthopaedic devices approved between 2001 and 2015. Utilizing the FDA's online public database, this systematic review audited study design and methodological variables intended to minimize bias and confounding. An additional analysis of blinding as well as the Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR NPT) was applied to the randomized controlled trials (RCTs). Of the 49 studies, 46 (94%) were prospective and 37 (76%) were randomized. Forty-seven (96%) of the studies were controlled in some form. Of 35 studies that reported it, blinding was utilized in 21 (60%), of which 8 (38%) were reported as single-blinded and 13 (62%) were reported as double-blinded. Of the 37 RCTs, outcome assessors were clearly blinded in 6 (16%), whereas 15 (41%) were deemed impossible to blind as implants could be readily discerned on imaging. When the CLEAR NPT was applied to the 37 RCTs, >70% of studies were deemed "unclear" in describing generation of allocation sequences, treatment allocation concealment, and adequate blinding of participants and outcome assessors. This study manifests the highly variable reporting and strength of clinical research methodology accepted by the FDA to approve high-risk orthopaedic devices.

Study on nondestructive discrimination of genuine and counterfeit wild ginsengs using NIRS

NASA Astrophysics Data System (ADS)

Lu, Q.; Fan, Y.; Peng, Z.; Ding, H.; Gao, H.

2012-07-01

A new approach for the nondestructive discrimination between genuine wild ginsengs and the counterfeit ones by near infrared spectroscopy (NIRS) was developed. Both discriminant analysis and back propagation artificial neural network (BP-ANN) were applied to the model establishment for discrimination. Optimal modeling wavelengths were determined based on the anomalous spectral information of counterfeit samples. Through principal component analysis (PCA) of various wild ginseng samples, genuine and counterfeit, the cumulative percentages of variance of the principal components were obtained, serving as a reference for principal component (PC) factor determination. Discriminant analysis achieved an identification ratio of 88.46%. With sample' truth values as its outputs, a three-layer BP-ANN model was built, which yielded a higher discrimination accuracy of 100%. The overall results sufficiently demonstrate that NIRS combined with BP-ANN classification algorithm performs better on ginseng discrimination than discriminant analysis, and can be used as a rapid and nondestructive method for the detection of counterfeit wild ginsengs in food and pharmaceutical industry.

Impact of fixation artifacts and threshold selection on high resolution melting analysis for KRAS mutation screening.

PubMed

Pérez-Báez, Wendy; García-Latorre, Ethel A; Maldonado-Martínez, Héctor Aquiles; Coronado-Martínez, Iris; Flores-García, Leonardo; Taja-Chayeb, Lucía

2017-10-01

Treatment in metastatic colorectal cancer (mCRC) has expanded with monoclonal antibodies targeting epidermal growth factor receptor, but is restricted to patients with a wild-type (WT) KRAS mutational status. The most sensitive assays for KRAS mutation detection in formalin-fixed paraffin embedded (FFPE) tissues are based on real-time PCR. Among them, high resolution melting analysis (HRMA), is a simple, fast, highly sensitive, specific and cost-effective method, proposed as adjunct for KRAS mutation detection. However the method to categorize WT vs mutant sequences in HRMA is not clearly specified in available studies, besides the impact of FFPE artifacts on HRMA performance hasn't been addressed either. Avowedly adequate samples from 104 consecutive mCRC patients were tested for KRAS mutations by Therascreen™ (FDA Validated test), HRMA, and HRMA with UDG pre-treatment to reverse FFPE fixation artifacts. Comparisons of KRAS status allocation among the three methods were done. Focusing on HRMA as screening test, ROC curve analyses were performed for HRMA and HMRA-UDG against Therascreen™, in order to evaluate their discriminative power and to determine the threshold of profile concordance between WT control and sample for KRAS status determination. Comparing HRMA and HRMA-UDG against Therascreen™ as surrogate gold standard, sensitivity was 1 for both HRMA and HRMA-UDG; and specificity and positive predictive values were respectively 0.838 and 0.939; and 0.777 and 0.913. As evaluated by the McNemar test, HRMA-UDG allocated samples to a WT/mutated genotype in a significatively different way from HRMA (p > 0.001). On the other hand HRMA-UDG did not differ from Therascreen™ (p = 0.125). ROC-curve analysis showed a significant discriminative power for both HRMA and HRMA-UDG against Therascreen™ (respectively, AUC of 0.978, p > 0.0001, CI 95% 0.957-0.999; and AUC of 0.98, p > 0.0001, CI 95% 0.000-1.0). For HRMA as a screening tool, the best threshold (degree of concordance between sample curves and WT control) was attained at 92.14% for HRMA (specificity of 0.887), and at 92.55% for HRMA-UDG (specificity of 0.952). HRMA is a highly sensitive method for KRAS mutation detection, with apparently adequate and statistically significant discriminative power. FFPE sample fixation artifacts have an impact on HRMA results, so for HRMA on FFPE samples pre-treatment with UDG should be strongly suggested. The choice of the threshold for melting curve concordance has also great impact on HRMA performance. A threshold of 93% or greater might be adequate if using HRMA as a screening tool. Further validation of this threshold is required. Copyright © 2017 Elsevier Ltd. All rights reserved.

FDA 101: Regulating Biological Products

MedlinePlus

... Home For Consumers Consumer Updates FDA 101: Regulating Biological Products Share Tweet Linkedin Pin it More sharing ... about this diverse and highly important field. What biological products does FDA regulate? The Center for Biologics ...

Frequency and level of evidence used in recommendations by the National Comprehensive Cancer Network guidelines beyond approvals of the US Food and Drug Administration: retrospective observational study.

PubMed

Wagner, Jeffrey; Marquart, John; Ruby, Julia; Lammers, Austin; Mailankody, Sham; Kaestner, Victoria; Prasad, Vinay

2018-03-07

To determine the differences between recommendations by the National Comprehensive Cancer Network (NCNN) guidelines and Food and Drug Administration approvals of anticancer drugs, and the evidence cited by the NCCN to justify recommendations where differences exist. Retrospective observational study. National Comprehensive Cancer Network and FDA. 47 new molecular entities approved by the FDA between 2011 and 2015. Comparison of all FDA approved indications (new and supplemental) with all NCCN recommendations as of 25 March 2016. When the NCCN made recommendations beyond the FDA's approvals, the recommendation was classified and the cited evidence noted. 47 drugs initially approved by the FDA between 2011 and 2015 for adult hematologic or solid cancers were examined. These 47 drugs were authorized for 69 FDA approved indications, whereas the NCCN recommended these drugs for 113 indications, of which 69 (62%) overlapped with the 69 FDA approved indications and 44 (39%) were additional recommendations. The average number of recommendations beyond the FDA approved indications was 0.92. 23% (n=10) of the additional recommendations were based on evidence from randomized controlled trials, and 16% (n=7) were based on evidence from phase III studies. During 21 months of follow-up, the FDA granted approval to 14% (n=6) of the additional recommendations. The NCCN frequently recommends beyond the FDA approved indications even for newer, branded drugs. The strength of the evidence cited by the NCCN supporting such recommendations is weak. Our findings raise concern that the NCCN justifies the coverage of costly, toxic cancer drugs based on weak evidence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Perceived Discrimination and Health: A Meta-Analytic Review

PubMed Central

Pascoe, Elizabeth A.; Richman, Laura Smart

2009-01-01

Perceived discrimination has been studied with regard to its impact on several types of health effects. This meta-analysis provides a comprehensive account of the relationships between multiple forms of perceived discrimination and both mental and physical health outcomes. In addition, this meta-analysis examines potential mechanisms by which perceiving discrimination may affect health, including through psychological and physiological stress responses and health behaviors. Analysis of 134 samples suggests that when weighting each study’s contribution by sample size, perceived discrimination has a significant negative effect on both mental and physical health. Perceived discrimination also produces significantly heightened stress responses and is related to participation in unhealthy and nonparticipation in healthy behaviors. These findings suggest potential pathways linking perceived discrimination to negative health outcomes. PMID:19586161

21 CFR 814.84 - Reports.

Code of Federal Regulations, 2011 CFR

2011-04-01

... be reported to FDA under § 814.39(b). (2) Contain a summary and bibliography of the following... bibliography, FDA concludes that the agency needs a copy of the unpublished or published reports, FDA will...

36 CFR 13.976 - Fire.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (fda) § 13.976 Fire. Lighting or maintaining a fire is prohibited in the FDA except— (a) In established receptacles within designated campgrounds; (b) From October 1 through April 14 in that portion of the FDA...

36 CFR 13.976 - Fire.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (fda) § 13.976 Fire. Lighting or maintaining a fire is prohibited in the FDA except— (a) In established receptacles within designated campgrounds; (b) From October 1 through April 14 in that portion of the FDA...

36 CFR 13.976 - Fire.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (fda) § 13.976 Fire. Lighting or maintaining a fire is prohibited in the FDA except— (a) In established receptacles within designated campgrounds; (b) From October 1 through April 14 in that portion of the FDA...

Prescription Weight-Loss Drugs: Can They Help You?

MedlinePlus

... term pharmacotherapy for obesity and overweight: Updated meta-analysis. BMJ. 2007;335:1194. Meridia (sibutramine): Market withdrawal due to risk of serious cardiovascular events. U.S. Food and Drug Administration. http://www.fda.gov/Safety/ ...

21 CFR 314.107 - Effective date of approval of a 505(b)(2) application or abbreviated new drug application under...

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... application for a drug product becomes effective on the date FDA issues an approval letter under § 314.105 for... on the date FDA issues an approval letter under § 314.105 if the applicant certifies under § 314.50(i...

21 CFR 314.107 - Effective date of approval of a 505(b)(2) application or abbreviated new drug application under...

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... application for a drug product becomes effective on the date FDA issues an approval letter under § 314.105 for... on the date FDA issues an approval letter under § 314.105 if the applicant certifies under § 314.50(i...

21 CFR 1.405 - When does FDA have to issue a decision on an appeal?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false When does FDA have to issue a decision on an... Consumption What Is the Appeal Process for A Detention Order? § 1.405 When does FDA have to issue a decision... final decision within the 5-calendar day period after the appeal is filed. If FDA either fails to...

21 CFR 803.3 - How does FDA define the terms used in this part?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false How does FDA define the terms used in this part... § 803.3 How does FDA define the terms used in this part? Some of the terms we use in this part are..., repairs, or upgrades, for an estimated period of time. FDA, we, or us means the Food and Drug...

21 CFR 1.405 - When does FDA have to issue a decision on an appeal?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false When does FDA have to issue a decision on an... Consumption What Is the Appeal Process for A Detention Order? § 1.405 When does FDA have to issue a decision... final decision within the 5-calendar day period after the appeal is filed. If FDA either fails to...

21 CFR 314.107 - Effective date of approval of a 505(b)(2) application or abbreviated new drug application under...

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... application for a drug product becomes effective on the date FDA issues an approval letter under § 314.105 for... on the date FDA issues an approval letter under § 314.105 if the applicant certifies under § 314.50(i...

21 CFR 1.405 - When does FDA have to issue a decision on an appeal?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false When does FDA have to issue a decision on an... Consumption What Is the Appeal Process for A Detention Order? § 1.405 When does FDA have to issue a decision... final decision within the 5-calendar day period after the appeal is filed. If FDA either fails to...

21 CFR 314.107 - Effective date of approval of a 505(b)(2) application or abbreviated new drug application under...

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... application for a drug product becomes effective on the date FDA issues an approval letter under § 314.105 for... on the date FDA issues an approval letter under § 314.105 if the applicant certifies under § 314.50(i...

21 CFR 1.405 - When does FDA have to issue a decision on an appeal?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false When does FDA have to issue a decision on an... Consumption What Is the Appeal Process for A Detention Order? § 1.405 When does FDA have to issue a decision... final decision within the 5-calendar day period after the appeal is filed. If FDA either fails to...

21 CFR 1.405 - When does FDA have to issue a decision on an appeal?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false When does FDA have to issue a decision on an... Consumption What Is the Appeal Process for A Detention Order? § 1.405 When does FDA have to issue a decision... final decision within the 5-calendar day period after the appeal is filed. If FDA either fails to...

21 CFR 314.107 - Effective date of approval of a 505(b)(2) application or abbreviated new drug application under...

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated... application for a drug product becomes effective on the date FDA issues an approval letter under § 314.105 for... on the date FDA issues an approval letter under § 314.105 if the applicant certifies under § 314.50(i...

Beyond C, H, O, and N! Analysis of the elemental composition of U.S. FDA approved drug architectures.

PubMed

Smith, Brandon R; Eastman, Candice M; Njardarson, Jon T

2014-12-11

The diversity of elements among U.S. Food and Drug Administration (FDA) approved pharmaceuticals is analyzed and reported, with a focus on atoms other than carbon, hydrogen, oxygen, and nitrogen. Our analysis reveals that sulfur, chlorine, fluorine, and phosphorous represent about 90% of elemental substitutions, with sulfur being the fifth most used element followed closely by chlorine, then fluorine and finally phosphorous in the eighth place. The remaining 10% of substitutions are represented by 16 other elements of which bromine, iodine, and iron occur most frequently. The most detailed parts of our analysis are focused on chlorinated drugs as a function of approval date, disease condition, chlorine attachment, and structure. To better aid our chlorine drug analyses, a new poster showcasing the structures of chlorinated pharmaceuticals was created specifically for this study. Phosphorus, bromine, and iodine containing drugs are analyzed closely as well, followed by a discussion about other elements.

Study on bayes discriminant analysis of EEG data.

PubMed

Shi, Yuan; He, DanDan; Qin, Fang

2014-01-01

In this paper, we have done Bayes Discriminant analysis to EEG data of experiment objects which are recorded impersonally come up with a relatively accurate method used in feature extraction and classification decisions. In accordance with the strength of α wave, the head electrodes are divided into four species. In use of part of 21 electrodes EEG data of 63 people, we have done Bayes Discriminant analysis to EEG data of six objects. Results In use of part of EEG data of 63 people, we have done Bayes Discriminant analysis, the electrode classification accuracy rates is 64.4%. Bayes Discriminant has higher prediction accuracy, EEG features (mainly αwave) extract more accurate. Bayes Discriminant would be better applied to the feature extraction and classification decisions of EEG data.

Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010

PubMed Central

Downing, Nicholas S.; Shah, Nilay D.; Aminawung, Jenerius A.; Pease, Alison M.; Zeitoun, Jean-David; Krumholz, Harlan M.

2017-01-01

Importance Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. Objectives To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. Design and Setting Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. Exposures Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near–regulatory deadline approval, and regulatory review time. Main Outcomes and Measures A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. Results From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval (IRR = 2.20; 95% CI, 1.15-4.21; P = .02), and those with near–regulatory deadline approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02). Conclusions and Relevance Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were affected by a postmarket safety event. Biologics, psychiatric therapeutics, and accelerated and near–regulatory deadline approval were statistically significantly associated with higher rates of events, highlighting the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle. PMID:28492899

Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010.

PubMed

Downing, Nicholas S; Shah, Nilay D; Aminawung, Jenerius A; Pease, Alison M; Zeitoun, Jean-David; Krumholz, Harlan M; Ross, Joseph S

2017-05-09

Postmarket safety events of novel pharmaceuticals and biologics occur when new safety risks are identified after initial regulatory approval of these therapeutics. These safety events can change how novel therapeutics are used in clinical practice and inform patient and clinician decision making. To characterize the frequency of postmarket safety events among novel therapeutics approved by the US Food and Drug Administration (FDA), and to examine whether any novel therapeutic characteristics known at the time of FDA approval were associated with increased risk. Cohort study of all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010, followed up through February 28, 2017. Novel therapeutic characteristics known at the time of FDA approval, including drug class, therapeutic area, priority review, accelerated approval, orphan status, near-regulatory deadline approval, and regulatory review time. A composite of (1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications. From 2001 through 2010, the FDA approved 222 novel therapeutics (183 pharmaceuticals and 39 biologics). There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years (interquartile range [IQR], 8.7-13.8 years), affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years (IQR, 2.5-6.0 years), and the proportion of novel therapeutics affected by a postmarket safety event at 10 years was 30.8% (95% CI, 25.1%-37.5%). In multivariable analysis, postmarket safety events were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93; 95% CI, 1.06-3.52; P = .03), therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval (IRR = 2.20; 95% CI, 1.15-4.21; P = .02), and those with near-regulatory deadline approval (IRR = 1.90; 95% CI, 1.19-3.05; P = .008); events were statistically significantly less frequent among those with regulatory review times less than 200 days (IRR = 0.46; 95% CI, 0.24-0.87; P = .02). Among 222 novel therapeutics approved by the FDA from 2001 through 2010, 32% were affected by a postmarket safety event. Biologics, psychiatric therapeutics, and accelerated and near-regulatory deadline approval were statistically significantly associated with higher rates of events, highlighting the need for continuous monitoring of the safety of novel therapeutics throughout their life cycle.

Safety and Procedural Success of Left Atrial Appendage Exclusion With the Lariat Device: A Systematic Review of Published Reports and Analytic Review of the FDA MAUDE Database.

PubMed

Chatterjee, Saurav; Herrmann, Howard C; Wilensky, Robert L; Hirshfeld, John; McCormick, Daniel; Frankel, David S; Yeh, Robert W; Armstrong, Ehrin J; Kumbhani, Dharam J; Giri, Jay

2015-07-01

The Lariat device has received US Food and Drug Administration (FDA) 510(k) clearance for soft-tissue approximation and is being widely used off-label for left atrial appendage (LAA) exclusion. A comprehensive analysis of safety and effectiveness has not been reported. To perform a systematic review of published literature to assess safety and procedural success, defined as successful closure of the LAA during the index procedure, of the Lariat device. We performed a formal analytic review of the FDA MAUDE (Manufacturer and User Facility Device Experience) database to compile adverse event reports from real-world practice with the Lariat. For the systematic review, PubMed, EMBASE, CINAHL, and the Cochrane Library were searched from January 2007 through August 2014 to identify all studies reporting use of the Lariat device in 3 or more patients. The FDA MAUDE database was queried for adverse events reports related to Lariat use. Data were abstracted in duplicate by 2 physician reviewers. Events from published literature were pooled using a generic inverse variance weighting with a random effects model. Cumulative and individual adverse events were also reported using the FDA MAUDE data set. Procedural adverse events and procedural success. In the systematic review, 5 reports of Lariat device use in 309 participants were identified. Specific complications weighted for inverse of variance of individual studies were urgent need for cardiac surgery (2.3%; 7 of 309 procedures) and death (0.3%; 1 of 309 procedures). Procedural success was 90.3% (279 of 309 procedures). In the FDA MAUDE database, there were 35 unique reports of adverse events with use of the Lariat device. Among these, we identified 5 adverse event reports that noted pericardial effusion and death and an additional 23 reported urgent cardiac surgery without mention of death. This review of published reports and case reports identified risks of adverse events with off-label use of the Lariat device for LAA exclusion. Formal, controlled investigations into the safety and efficacy of the device for this indication are warranted.

Comparative Assessment of Off-label and Unlicensed Drug Prescriptions in Children: FDA Versus ANSM Guidelines.

PubMed

Berdkan, Sandra; Rabbaa, Lara; Hajj, Aline; Eid, Bassam; Jabbour, Hicham; Osta, Nada El; Karam, Latife; Khabbaz, Lydia Rabbaa

2016-08-01

The main objectives of this study were to assess the incidence of off-label (OL) and/or unlicensed (UL) prescriptions in a sample of pediatric Lebanese patients by using US Food and Drug Administration (FDA) and the French Medical Regulatory Authority (ANSM) regulations. The goal was to analyze the divergences between regulations and to identify those drugs most commonly involved in OL-UL utilization. This study was a retrospective analysis (500 pediatric files) conducted in a Lebanese University hospital in 3 pediatric wards (chronic diseases, acute diseases, and the pediatric intensive care unit). The frequency of OL-UL drug use was significantly different between pediatric wards (P < 0.001), with the highest incidence occurring in the intensive care unit. The most frequent OL-UL prescriptions occurred with cancer (oncology) admissions. Age was significantly related to OL-UL frequency (highest incidence in children aged between 0 and 1 year). The number of drugs prescribed per patient ranged between 1 and 20 (mean [SD], 4.13 [2.6]). The incidence of OL-UL prescriptions was significantly higher in patients treated with a greater number of medicines (P < 0.001). Overall, 58.9% of drug prescriptions were authorized according to ANSM and 50.7% according to FDA regulations; 11.1% (ANSM) and 15.8% (FDA) were UL, and 30.2% (ANSM) and 33.5% (FDA), respectively, were OL use (where OL for the indication were the most common). The highest percentage of OL-UL prescriptions was seen with the following groups: blood and blood-forming organs, genitourinary system, and sex hormones. Divergence between FDA and ANSM was mainly observed for OL medicines. UL prescriptions assessed according to both regulations showed similar results. This study highlights the need for prescribers to continuously examine updates to official regulations to avoid using an OL-UL drug whenever possible. It also calls for better harmonization between worldwide official guidelines concerning drugs used in children to reduce risk factors for adverse drug reactions. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Publication Bias in Antipsychotic Trials: An Analysis of Efficacy Comparing the Published Literature to the US Food and Drug Administration Database

PubMed Central

Turner, Erick H.; Knoepflmacher, Daniel; Shapley, Lee

2012-01-01

Background Publication bias compromises the validity of evidence-based medicine, yet a growing body of research shows that this problem is widespread. Efficacy data from drug regulatory agencies, e.g., the US Food and Drug Administration (FDA), can serve as a benchmark or control against which data in journal articles can be checked. Thus one may determine whether publication bias is present and quantify the extent to which it inflates apparent drug efficacy. Methods and Findings FDA Drug Approval Packages for eight second-generation antipsychotics—aripiprazole, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting injection (risperidone LAI), and ziprasidone—were used to identify a cohort of 24 FDA-registered premarketing trials. The results of these trials according to the FDA were compared with the results conveyed in corresponding journal articles. The relationship between study outcome and publication status was examined, and effect sizes derived from the two data sources were compared. Among the 24 FDA-registered trials, four (17%) were unpublished. Of these, three failed to show that the study drug had a statistical advantage over placebo, and one showed the study drug was statistically inferior to the active comparator. Among the 20 published trials, the five that were not positive, according to the FDA, showed some evidence of outcome reporting bias. However, the association between trial outcome and publication status did not reach statistical significance. Further, the apparent increase in the effect size point estimate due to publication bias was modest (8%) and not statistically significant. On the other hand, the effect size for unpublished trials (0.23, 95% confidence interval 0.07 to 0.39) was less than half that for the published trials (0.47, 95% confidence interval 0.40 to 0.54), a difference that was significant. Conclusions The magnitude of publication bias found for antipsychotics was less than that found previously for antidepressants, possibly because antipsychotics demonstrate superiority to placebo more consistently. Without increased access to regulatory agency data, publication bias will continue to blur distinctions between effective and ineffective drugs. Please see later in the article for the Editors' Summary PMID:22448149

Trials of transvaginal mesh devices for pelvic organ prolapse: a systematic database review of the US FDA approval process.

PubMed

Heneghan, Carl J; Goldacre, Ben; Onakpoya, Igho; Aronson, Jeffrey K; Jefferson, Tom; Pluddemann, Annette; Mahtani, Kamal R

2017-12-06

Transvaginal mesh devices are approved in the USA by the Food and Drug Administration (FDA), through the 510(k) system. However, there is uncertainty about the benefit to harm balance of mesh approved for pelvic organ prolapse. We, therefore, assessed the evidence at the time of approval for transvaginal mesh products and the impact of safety studies the FDA mandated in 2012 because of emerging harms. We used FDA databases to determine the evidence for approval of transvaginal mesh. To create a 'family tree' of device equivalence, we used the 510(k) regulatory approval of the 1985 Mersilene Mesh (Ethicon) and the 1996 ProteGen Sling (Boston Scientific), searched for all subsequently related device approvals, and for the first published randomised trial evidence. We assessed compliance with all FDA 522 orders issued in 2012 requiring postmarketing surveillance studies. We found 61 devices whose approval ultimately relied on claimed equivalence to the Mersilene Mesh and the ProteGen Sling. We found no clinical trials evidence for these 61 devices at the time of approval. Publication of randomised clinical trials occurred at a median of 5 years after device approval (range 1-14 years). Analysis of 119 FDA 522 orders revealed that in 79 (66%) the manufacturer ceased market distribution of the device, and in 26 (22%) the manufacturer had changed the indication. Only seven studies (six cohorts and new randomised controlled trial) covering 11 orders were recruiting participants (none had reported outcomes). Transvaginal mesh products for pelvic organ prolapse have been approved on the basis of weak evidence over the last 20 years. Devices have inherited approval status from a few products. A publicly accessible registry of licensed invasive devices, with details of marketing status and linked evidence, should be created and maintained at the time of approval. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.