At the beginning of Lionberger’s talk, titled, “New Tools for Generic Orally Inhaled Drug Products to Maximize Prospects of Food and Drug Administration Approval,” he specifically thanked Rob Price and Jag Shur of the University of Bath and Nanopharm who, he said, “Really helped us to understand how difficult it is to develop these products.”
Lionberger, who has been the Director of the Office of Research and Standards in the Office of Generic Drugs since 2014 says that he understands the difficulty for developers of generic OINDPs, quipping that “Generic companies don’t have to hit the target, they have to hit your bullet.”
He explained that the OGD is trying to enlist physics to help them understand the complexities of inhalation products and discussed three tools that the FDA has explored for assistance in establishing bioequivalence: CFD, dissolution testing, and realistic mouth-throat models. Research priorities for 2018 that he mentioned include physiologically based pharmacokinetic (PBPK) modeling and alternatives to clinical endpoints. The goal, he said, is to get more generic competition faster.
In the first of three talks on analytical techniques in the session, Sandell discussed a multi-batch approach to PK bio-equivalence studies designed to deal with a reference product that has high batch-to-batch variability, saying that the approach “ensures that the BE results apply to the products rather than to the batches.”
In December 2017, Mylan filed a citizen petition challenging the use of multi-batch PK BE studies to support an ANDA for a generic version of Advair Diskus, targeting an ANDA submitted by Sandoz.
Price described determination of Q3 structural equivalence (same components in same concentration with the same microstructure) for DPI formulations) with morphologically-directed raman spectroscopy (MDRS) and dissolution testing using Nanopharm’s UniDose collection system.
Stein presented recommendations for best practices for cascade impactor testing for passive DPIs, particularly emphasizing the need to distinguish between quality control methods of cascade impaction and clinically relevant methods.
