GMPs for Method Validation in Early Development: An Industry Perspective (Part II)

By Donald Chambers, Gary Guo, Brent Kleintop, Henrik Rasmussen, Steve Deegan, Steven Nowak, Kristin Patterson, John Spicuzza, Michael Szulc, Karla Tombaugh, Mark D. Trone and Zhanna Yuabova.

The International Consortium on Innovation and Quality in Pharmaceutical Development (IQ) was formed in 2010 as an association of over 25 pharmaceutical and biotechnology companies with a mission to advance science-based and scientifically-driven standards and regulations for medicinal products worldwide. In the July 2012 issue of Pharmaceutical Technology Europe , a paper was presented which described an overview of IQs consolidated recommendations from the Good Manufacturing Practices (GMPs) in Early Development working group (WG) (1). The focus of this IQ WG has been to develop recommended approaches on how to apply GMPs in early phase CMC development activities covering Phase I through Phase IIa. A key premise of the GMPs in Early Development WG is that existing GMP guidances for early development are vague and that improved clarity in the definition of GMP expectations would advance innovation in small-molecule pharmaceutical development by improving cycle times and reducing costs, while maintaining appropriate product quality and ensuring patient safety.

A consequence of the absence of clarity surrounding early phase GMP expectations has been varied in interpretation and application of existing GMP guidances across the industry depending on an individual company’s own culture and risk tolerance. Internal debates within a company have frequently resulted in inappropriate application of conservative “one-size-fits-all” interpretations that rely on guidelines from the International Conference on Harmonisation (ICH) that are more appropriate for pharmaceutical products approaching the point of marketing authorisation application. In many cases, erroneous application of these commercial ICH GMP expectations during early clinical development does not distinguish the distinct differences in requirements between early development and late-stage development (Phase IIb and beyond). A key objective of this IQ WG, therefore, has been to collectively define in early development--within acceptable industry practices--some GMP expectations that allow for appropriate flexibility and that are consistent with existing regulatory guidances and statutes (2).