Within this paper, IQ representatives have presented an industry perspective on appropriate requirements and considerations
for early phase analytical method validation. A suggested outline of acceptable experiments that ensure analytical procedures
developed to support API and drug product production of early phase clinical materials are suitable for their intended use
has been presented. Additionally, the authors have provided a position on phased approaches to other aspects of method validation
such as documentation requirements, generation of method validation plans, validation criteria, and the strategic involvement
of quality unit oversight. When applied appropriately, this approach can help to ensure pharmaceutical development organizations
provide appropriate analytical controls for API and drug product processes which will serve the ultimate goal of ensuring
patient safety. Although the extent of early-phase method validation experiments is appropriately less than employed in the
later stages of development, we view that any risks related to this approach will not be realized, especially when considering
the overall quality and safety approach used by pharmaceutical companies for early phase clinical studies.
It is the authors' hope that providing such an approach to early-phase method validation, along with the approaches outlined
in this series of early-phase GMP papers, will serve as a springboard to stimulate discussions on these approaches within
the industry and with worldwide health authorities. To encourage further dialogue, this IQ working group is planning on conducting
a workshop in the near future to promote robust debate and discussion on these recommended approaches to GMPs in early development.
These discussions will ideally enable improved alignment between R&D development, Quality, and CMC regulatory organizations
across the pharmaceutical industry, and most importantly with worldwide regulatory authorities. Agreement between industry
and health authorities regarding acceptable practices to applying GMPs in the early phases of drug development would clearly
be beneficial to CMC pharmaceutical development scientists and allow for a more nimble and flexible approach to better address
the dynamic environment typical of the early phases of clinical development, while still guaranteeing appropriate controls
to ensure patient safety during early development.
Donald Chambers is in analytical sciences at Merck Research Laboratories, Gary Guo is in analytical R&D at Amgen, Brent Kleintop* is in analytical and bioanalytical development at Bristol-Myers Squibb Co., Henrik Rasmussen is in analytical development at Vertex Pharmaceuticals, Steve Deegan is in GMP Quality Assurance Operations at Abbott, Steven Nowak is in NCE Analytical R&D, Global Pharmaceutical R&D, at Abbott, Kristin Patterson is in emerging markets R&D at GlaxoSmithKline, John Spicuzza is in analytical development at Baxter, Michael Szulc is in analytical development at Bioden Idec, Karla Tombaugh is in R&D/Commercialization Quality, Merck Manufacturing Division, at Merck & Co., Mark D. Trone is in analytical development, small molecule, at Millennium Pharmaceuticals, and Zhanna Yuabova is in analytical development, US, at Boehringer Ingelheim Pharmaceuticals.
*To whom all correspondence should be addressed.