Scientific and regulatory activities initiated by the U.S. Food and drug administration to foster approvals of generic dry powder inhalers: Bioequivalence perspective.

Regulatory science for generic dry powder inhalers (DPIs) in the United States (U.S.) has evolved over the last decade. In 2013, the U.S. Food and Drug Administration (FDA) published the draft product-specific guidance (PSG) for fluticasone propionate and salmeterol xinafoate inhalation powder. This was the first PSG for a DPI available in the U.S., which provided details on a weight-of-evidence approach for establishing bioequivalence (BE). A variety of research activities including in vivo and in vitro studies were used to support these recommendations, which have led to the first approval of a generic DPI in the U.S. for fluticasone propionate and salmeterol xinafoate inhalation powder in January of 2019. This review describes the scientific and regulatory activities that have been initiated by FDA to support the current BE recommendations for DPIs that led to the first generic DPI approvals, as well as research with novel in vitro and in silico methods that may potentially facilitate generic DPI development and approval.

Scientific and regulatory activities initiated by the U.S. food and drug administration to foster approvals of generic dry powder inhalers: Quality perspective.

Regulatory science for generic dry powder inhalation products worldwide has evolved over the last decade. The revised draft guidance Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Products - Quality Considerations [1] (Revision 1, April 2018) that FDA issued summarizes product considerations and potential critical quality attributes (CQAs). This guidance emphasizes the need to apply the principles of quality by design (QbD) and elements of pharmaceutical development discussed in the International Conference for Harmonisation of (ICH) guidelines. Research studies related to quality were used to support guidance recommendations, which preceded the first approval of a generic DPI product in the U.S. This review outlines scientific and regulatory hurdles that need to be surmounted to successfully bring a generic DPI to the market. The goal of this review focuses on relevant issues and various challenges pertaining to CMC topics of the generic DPI quality attributes. Furthermore, this review provides recommendations to abbreviated new drug application (ANDA) applicants to expedite generic approvals.

The social mission of medical education: ranking the schools.

BACKGROUND: The basic purpose of medical schools is to educate physicians to care for the national population. Fulfilling this goal requires an adequate number of primary care physicians, adequate distribution of physicians to underserved areas, and a sufficient number of minority physicians in the workforce. OBJECTIVE: To develop a metric called the social mission score to evaluate medical school output in these 3 dimensions. DESIGN: Secondary analysis of data from the American Medical Association (AMA) Physician Masterfile and of data on race and ethnicity in medical schools from the Association of American Medical Colleges and the Association of American Colleges of Osteopathic Medicine. SETTING: U.S. medical schools. PARTICIPANTS: 60 043 physicians in active practice who graduated from medical school between 1999 and 2001. MEASUREMENTS: The percentage of graduates who practice primary care, work in health professional shortage areas, and are underrepresented minorities, combined into a composite social mission score. RESULTS: The contribution of medical schools to the social mission of medical education varied substantially. Three historically black colleges had the highest social mission rankings. Public and community-based medical schools had higher social mission scores than private and non-community-based schools. National Institutes of Health funding was inversely associated with social mission scores. Medical schools in the northeastern United States and in more urban areas were less likely to produce primary care physicians and physicians who practice in underserved areas. LIMITATIONS: The AMA Physician Masterfile has limitations, including specialty self-designation by physicians, inconsistencies in reporting work addresses, and delays in information updates. The public good provided by medical schools may include contributions not reflected in the social mission score. The study was not designed to evaluate quality of care provided by medical school graduates. CONCLUSION: Medical schools vary substantially in their contribution to the social mission of medical education. School rankings based on the social mission score differ from those that use research funding and subjective assessments of school reputation. These findings suggest that initiatives at the medical school level could increase the proportion of physicians who practice primary care, work in underserved areas, and are underrepresented minorities.

Extraction of alternative fuels from fire debris samples*.

Alternative fuels, specifically biodiesel, biodiesel blends, and E85 fuel, have been gaining a market share over the past few years. With the emergence of these fuels, fire debris analysts should be able to recognize their characteristics since these fuels may be encountered in casework. In this study, pure biodiesel (B100) and a 20% blend of pure biodiesel with petroleum diesel (B20) are examined as liquids and are extracted from debris samples using both passive headspace concentration and solvent extraction. Typical fire debris instrumental conditions are used to analyze these samples. Components of B100 and B20 may be observed in debris samples extracted using the passive headspace concentration method, but the chromatographic patterns are different from the pure liquid samples. When solvent extraction is used as a secondary extraction method on debris samples, the resulting patterns are consistent with the pure liquids of B100 and B20. E85 fuel, a blend of 85% ethanol and 15% gasoline, can be extracted using a typical fire debris extraction technique but requires slight modifications to typical fire debris instrumental conditions. E85 is shown at various stages of evaporation to demonstrate the resiliency of the ethanol. Additionally, samples of E85 were placed on carpet, burned and extinguished to demonstrate the effects of the suppression medium on the retention of ethanol.