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By Sai Chamarthy, Philip Kuehl, and Jayne Hastedt

Sai Chamarthy-finalPhilip Kuehl-finalJayne Hastedt-finalSince 2000, developers of immediate-release oral drugs have been able to request waivers of in vivo bioequivalence studies based on the Food and Drug Administration’s (FDA’s) Biopharmaceutics Classification System (BCS). Based on the work of University of Michigan professor Gordon Amidon, the BCS has allowed more efficient development and regulatory review of immediate release oral drug products based on in vitro data. The oral BCS was originally published in 1995 and has been revisited several times by Amidon and his team(s): Dahan et al and Amidon et al. For oral products, the BCS approach has provided an effective means to develop high-throughput screening paradigms in early discovery, prioritizing development resources in early development and increasing market access due to generics through the waivers of in vivo bioequivalence studies.

Over the past 10 years, there has been an increased interest in dissolution testing of pulmonary drug products. In 2003, a position paper containing guidelines for dissolution testing of novel/special dosage forms was published. The authors proposed “first choice” test methods using existing apparatus for these novel/special dosage forms. A workshop conducted in 2008 was held on the in vitro drug release from special dosage forms. This workshop was the first to specifically discuss the role of dissolution for intranasal and inhalation products. In 2009, another workshop was held to review the latest advances in dissolution testing for novel dosage forms and resulted in an update to the 2003 publication on this topic. In this publication, the authors indicated that there might be value in understanding the drug release from inhaled particles and droplets deposited in the lung.

Obviously formulators are looking for science-based approaches to help speed the development and regulatory review of inhalation drug products. Is a BCS-like classification system the answer we are looking for? Developing such a classification system for inhaled drugs could lead to a better understanding of the key in vitro attributes impacting product bioperformance by “class” of drug and thus lead to similar streamlined development and regulatory benefits as achieved for immediate release oral products. The importance of a clear path for development of inhaled drugs was highlighted by the FDA issuing a Guidance (currently in draft format) specifically for a generic formulation of Fluticasone Propionate; Salmeterol Xinafoate (Advair).

An AAPS workshop sponsored by the AAPS Inhalation and Nasal Technology Focus Group, the United States Pharmacopeia (USP), and the FDA will explore this possibility. Inhalation Biopharmaceutical Product Classification System Development: Challenges and Opportunities will convene with leading orally inhaled drug product specialists to consider the biorelevance of in vitro parameters, particularly dissolution, permeability, and deposition.

Amidon will give the workshop’s keynote presentation and set the stage by discussing the history of the BCS for oral drug products. He will introduce the classification system, discuss its relevance to IVIVC and biowaivers, and review its limitations.

The program also will include a number of speakers from industry and academia who will discuss various factors critical to developing an inhalation BCS (iBCS) for orally inhaled drugs. The speakers will discuss lung physiology, PK/PD modeling for pulmonary delivery, dissolution testing for inhaled products, along with a few case studies of well characterized orally inhaled drugs.

The workshop will also integrate an interactive segment, beginning with a roundtable discussion of considerations for a small molecule classification system and followed by a trio of breakout sessions to discuss dose number, absorption number, and dissolution number in relation to a possible iBCS. Through the roundtable and breakout sessions, attendees will have the opportunity to provide input and feedback and thus influence the development of an iBCS.

The organizers will utilize the presentation materials and the roundtable discussions to prepare a series of white papers summarizing the findings from the workshop. The white papers will include scientific approaches that can be used to identify the critical in vitro product attributes and drug physical chemical properties to categorize pulmonary drugs and thus form the framework for and iBCS for immediate release orally inhaled products.

Inhalation Biopharmaceutical Product Classification System Development: Challenges and Opportunities will take place in Baltimore, March 16–17, 2015.

Sai Chamarthy, Ph.D., is an associate director at Merck, in Pharmaceutical Sciences & Clinical Supply, where he leads a group specializing in formulations, process development, and manufacturing of inhaled and nasal drug products.
Philip Kuehl, Ph.D., is a scientist within the Applied Science Department and is the director of the Scientific Core Laboratories at Lovelace Respiratory Research Institute.
Jayne Hastedt, Ph.D., is the managing director of JDP Pharma Consulting, LLC. She provides CMC support for pulmonary and other drug delivery platforms.