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12 Pharmaceutical Technology Europe BIO/PHARMA OUTSOURCING INNOVATION eBOOK 2022 P h a r mTe c h . c o m Analytics A nalytical methods and bioassays require a well- thought-out manner of evaluating method va- lidity (truthfulness) and systems suitability (a known positive control) to ensure the method is correct, reliable, and can be used to determine the value of the unknown test article. This paper recommends and explains methods for evaluating system suitability as well as validity criteria. Further, the paper discusses practical and phase-appropriate methods for setting limits for systems suitability and validity criteria. In alignment with guidances such as International Council of Harmonisation (ICH) Q2 (1), United States Pharmacopeia (USP) <1033>, <1032>, <1225>, and ICH Q6B (2), method de- velopment, validation and method understanding is a critical element of product measurement and control. Systems suit- ability should be understood to be separate from validity cri- teria. Systems suitability is defined as a known positive control that can be demonstrated to be within a defined set of limits. Validity criteria typically includes signal control for bioassay criteria for parallelism and linearity, and criteria for repeat- ability. It may further include a fixed number of outliers for data management. Systems suitability There are two methods for systems suitability. The first method involves adding a positive control to the assay run. The positive control is a known standard at a fixed concentra- tion. By adding the known standard to the plate and checking if it is within a defined limit, one can trust that the method is running correctly, and the test article may be reliably de- termined. The second method requires use of a standard curve. A standard curve or calibrator has a known value and is placed on the plate at three or more concentrations; a curve is then fit to the data. By measuring the concentration at a fixed position on the standard curve, one can use that data for systems suitability. The standard curve approach has a distinct advantage in reducing the analytical error of the quantitation of the positive control. It is not recommended Thomas A. Little * , PhD, drlittle@thomasalittleconsulting. com, is president and principle consultant of Bioassay Sciences, and Daniel S. Harding is a principle consultant of Bioassay Sciences. * To whom all correspondence should be addressed. TILIALUCIDA - STOCK.ADOBE.COM Establishing Systems Suitability and Validity Criteria for Analytical Methods and Bioassays Thomas A. Little and Daniel S. Harding Ensuring reliable analytical methods and bioassays requires a well-thought-out strategy for evaluating method validity and systems suitability.