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We characterized the size of the premarket safety population for 278 small-molecule new molecular entities (NMEs) and 61 new therapeutic biologics (NTBs) approved by the US Food and Drug Administration (FDA) between October 1, 2002, and December 31, 2014, evaluating the relationship of premarket safety population size to regulatory characteristics and postmarket safety outcomes. The median size of the safety population was 1,044, and was lower for NTBs than NMEs (median: 920 vs. 1,138, P = 0.04), orphan products than nonorphan products (393 vs. 1,606, P < 0.001), and for products with fast-track designation (617 vs. 1,455, P < 0.001), priority review (630 vs. 1,735, P < 0.001), and accelerated approval (475 vs. 1,164, P < 0.001), than products without that designation. The median number of postmarket safety label updates and issues added to the label were higher with larger premarket exposure among nonorphan products, but not among orphan products. Products with accelerated approval using a surrogate end point had a higher median number of safety issues added to the label than those with full approval, but this did not vary with the size of the safety population; fast-track and priority review were not associated with the number of safety issues added to the label. A smaller safety population size was associated with a longer time to first safety outcome for nonorphan products but not orphan products. For orphan and nonorphan products combined, smaller premarket safety population size is not associated with the number or timing of postmarket safety outcomes, regardless of expedited program participation., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

We examined the relationship of regulatory and review characteristics to postmarketing safety-related regulatory actions for 61 new therapeutic biologics (NTBs) approved between October 1, 2002 and December 31, 2014. We also compared NTBs with small-molecule new molecular entities (NMEs) on these measures. Postmarketing safety-related regulatory actions were defined as a safety-related withdrawal or a safety-related update to a safety section of the label through June 30, 2018. Four NTBs were withdrawn, two for safety reasons. At least one safety-related update was added to the labels of 54 (88.5%) NTBs. Label updates occurred throughout the follow-up period. Time to the first safety-related regulatory action was shorter for NTBs approved under accelerated approval. The occurrence of safety events was more likely to occur with NTBs than with NMEs. This may be explained in part by the higher proportion of NTBs in the anatomical therapeutic chemical classification categories with higher frequency of safety-related updates. NTBs also had shorter time to safety events than NMEs. These findings underscore the importance of continued development of the life cycle safety surveillance system for both drugs and biologics with consideration for product type and its characteristics, including pharmacologic action., (Published 2020. This article is a US Government work and is in the public domain in the USA.)

Background: We previously estimated that the annual rate of accidental exposure to peanut in 1411 children with peanut allergy, followed for 2227 patient-years, was 11.9% (95% CI, 10.6, 13.5). This cohort has increased to 1941 children, contributing 4589 patient-years, and we determined the annual incidence of accidental exposure, described the severity, management, location, and identified associated factors., Findings: Children with physician-confirmed peanut allergy were recruited from Canadian allergy clinics and allergy advocacy organizations from 2004 to May 2014. Parents completed questionnaires regarding accidental exposure to peanut over the preceding year. Five hundred and sixty-seven accidental exposures occurred in 429 children over 4589 patient-years, yielding an annual incidence rate of 12.4% (95% CI, 11.4, 13.4). Of 377 accidental exposures that were moderate or severe, only 109 (28.9%) sought medical attention and of these 109, only 40 (36.7%) received epinephrine. Of the 181 moderate/severe accidental exposures treated outside a health care facility, only 11.6% received epinephrine. Thirty-seven percent of accidental exposures occurred at home. In multivariate analyses, longer disease duration, recruitment through an allergy advocacy association, and having other food allergies decreased the likelihood of accidental exposures. Age ≥ 13 years at study entry and living with a single parent increased the risk., Conclusion: Despite increased awareness, accidental exposures continue to occur, mainly at home, and most are managed inappropriately by both health care professionals and caregivers. Consequently, more education is required on the importance of strict allergen avoidance and the need for prompt and correct management of anaphylaxis.

A focused microwave-assisted extraction method was developed for the extraction of diosgenin from fenugreek (Trigonella foenum-graecum) seeds, air-dried and fresh leaves and air-dried roots. Several experimental parameters were studied, including extraction time, microwave power applied and percentage of 2-propanol in the extraction mixture as well as their interactions, in order to optimize the extraction efficiency. The two latter parameters were found to be the most important. Response surface modelling was used to predict the extraction yield of diosgenin in selected matrices. The analysis of diosgenin in crude extracts was carried out by capillary gas chromatography-mass spectrometry (GC-MS).

High-performance capillary electrophoresis (HPCE) and micellar electrokinetic capillary chromatography (MECC) were applied to the resolution of racemic nonsteroidal antiaromatase drugs and intermediates. Successful results were obtained in both modes using alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), gamma-cyclodextrin (gamma-CD), or 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CD) as chiral selectors. Depending on the structure of the solute, one of the cyclodextrins was generally better suited for resolution of the racemate. The basic solutes were analyzed under HPCE conditions, whereas the nonionizable compounds such as glutethimide (Doriden) were analyzed in MECC mode. For the azole-type antiaromatase Fadrozole, both HPCE and MECC modes could be used to achieve the separation of the enantiomers. The influence of experimental factors such as pH, the presence of organic modifier, temperature, the micelle concentration, and the concentration of the chiral selector is also discussed on the basis of the results obtained with some chiral barbiturates. The possibility of analyzing the enantiomers directly in plasma samples was also demonstrated.