Search

In silico mechanistic modeling approaches have been designed by various stakeholders with the goal of supporting development and approval of generic orally inhaled drug products in the United States. This review summarizes the presentations and panel discussion that comprised a workshop session concentrated on the use of in silico models to predict various outcomes following orally inhaled drug product administration, including the status of such models and how model credibility may be effectively established.

Herein, we present the US Food and Drug Administration (FDA) Office of Research and Standards' current thinking, challenges, and opportunities for comparative clinical endpoint bioequivalence (BE) studies of orally inhaled drug products (OIDPs). Given the product-associated complexities of OIDPs, the FDA currently uses an aggregate weight-of-evidence approach to demonstrate that a generic OIDP is bioequivalent to its reference listed drug. The approach utilizes comparative clinical endpoint BE or pharmacodynamic BE studies, pharmacokinetic BE studies, and in vitro BE studies to demonstrate equivalence, in addition to formulation sameness and device similarity. For the comparative clinical endpoint BE studies, metrics based on forced expiratory volume in the first second (FEV

Background In the USA, drug costs associated with the inhaled corticosteroid (ICS) and long acting β agonist (LABA) combination products have been increasing since 2001. In January 2019, the first generic ICS/LABA drug product was approved by the U.S. Food and Drug Administration. Methods We investigated retrospectively the effects of the first approved generic ICS/LABA drug from 2019 to 2020 on the wholesale cost-savings and prescription dispensing using the IQVIA data system in the USA. Results The marketing of the first generic for fluticasone propionate and salmeterol xinafoate dry powder inhaler was associated with $941 million in drug cost-savings during the first year for this class of medications. Although the brand-name drug manufacturer concurrently introduced its authorized generic, these cost-savings were driven by the averaged unit cost of the approved generic at $115, compared to $169 for the authorized generic and $334 for the branded product. Generic initiation and substitution with the first generic were, respectively, higher compared to those with authorized generics; however, overall dispensing of the first generic was lower than that of its branded product. As in the case of budesonide and formoterol fumarate dry powder inhaler, marketing of authorized generics alone was not associated with any noticeable change in sales or prescription cost-saving. Conclusion We estimated that more than 20% of prescription cost-saving was achieved for the ICS/LABA dry powder inhalers in the first year following the introduction of the first approved generic, even though generic utilization remained lower than that of the branded counterpart.

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.

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.

Dr. Gavril Pasternak, M.D., Ph.D. was an inspiration to many of his students, including myself. It was with great sadness that I learned about the passing of Dr. Gavril Pasternak in February 2019 after his brief battle with pancreatic cancer. I worked with Dr. Pasternak while I was an undergraduate chemistry student and as one of his technicians, collaborating with Dr. Charles Inturrisi and Dr. Eliot F. Hahn on opiate agonists and antagonists for opioid receptor subtypes. Dr. Pasternak inspired me and set me on the road to a career in pharmacology and encouraged me to pursue the fruitful paradigm of moving therapeutics from bench to bedside.