Representatives from Merck, Pfizer, and Novartis shared their recent efforts in applying quality-by-design (QbD) concepts to analytical methods, and Todd Cecil from USP explained the related new draft USP chapter in a symposium at Pittcon on Monday, March 18, 2013. The session, “Understanding Analytical Method Variance and the Impact for QbD Filing for Pharmaceutical Products,” was sponsored by the American Chemical Society’s Division of Analytical Chemistry (ACS ANYL) and the American Association of Pharmaceutical Scientist’s Analysis and Pharmaceutical Quality Section (AAPS APQ).
In recent years, scientists have begun applying QbD concepts to analytical methods. An article in the March 2013 issue of Pharmaceutical Technology, “The Role of Analytical Science in Implementing Quality by Design,” discusses this topic and reviews the conclusions of a Parenteral Drug Association (PDA) workshop from March 2012 that provided a forum for stakeholders to explore the implications of QbD on analytical science. A QbD approach “highlights the potential to re-examine the way methods are developed and validated, in the same way that application of QbD to manufacturing processes has driven a revision in thinking of how process development and validation are performed,” say the article’s authors.
Speakers at the Pittcon symposium described some of their work in applying the systematic approach and formal risk-assessments of a QbD approach to analytical methods. Beth Junker of Merck, for example, described an “analytical target profile (ATP)” and talked about determining critical and key method attributes together with end-users of the method. Design of experiments (DOE) can help optimize methods. Dr. Junker noted that because most design of experiments (DOE) training and guidance materials are intended for process scientists, her group found it useful to assemble a design of experiments toolkit, including software training, specifically for use by analysts. She added that QbD for analytical methods can aid with planning method lifecycle activities and reduce unplanned resource demands. James Morgado from Pfizer described the “Method Operable Design Region (MODR),” and explained that defining the ATP, performing risk assessments, and conducting DOEs to determine risk results in the MODR.
Todd Cecil, vice-president of Compendial Science at the United States Pharmacopeia (USP), weighed in on defining acceptable analytical method variation and setting system suitability requirements. He described a new chapter, USP<1200>, with a working title “Requirements for Compendial Variation,” which introduces alternate tests (e.g., detectability instead of limit of detection) and reduces the total number of tests needed. Cecil noted that other industries (e.g., the food industry) have moved to this approach already and it will take time for it to be accepted by FDA, but that USP is moving forward.