RT Journal Article
SR Electronic
T1 Compendial Methods: Suitability Verification, Challenges and Recommendations for Proteins
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 581
OP 591
DO 10.5731/pdajpst.2019.010652
VO 74
IS 5
A1 Wen-Li Chung
A1 Jian Yin
A1 Steven Messick
A1 Miguel Saggu
A1 Kate Tschudi
A1 Ann Woys
A1 Rod Rahimi
A1 Marianne Azarias
A1 Connie Kong
A1 Bruce Kabakoff
YR 2020
UL http://journal.pda.org/content/74/5/581.abstract
AB Compendial testing methods are not required to be fully validated, but their suitability for testing should be verified under actual conditions of use. This requirement is established in 21 CFR 211.194(a)(2) of the current Good Manufacturing Practice regulations in the United States. ANVISA (Agência Nacional de Vigilância Sanitária) also requires that compendial analytical methods shall have their suitability demonstrated for the intended use by a partial validation study. Suitability verifications or partial validation can be divided into two major categories: visual and instrumental methods. For visual methods, the color and opalescence of interferences should be checked. If the color or clarity/opalescence of the sample is outside of the range of the Pharmacopeia standards/reference solutions, the validity of the test results should be evaluated. Specificity is usually waived because the methods are not specific to products, and accuracy/precision can be addressed by comparing results from analyst to analyst. For instrument methods, specificity can also be waived for certain assays. Accuracy is addressed by implementation of instrument calibration and/or method control. Precision is required either in suitability verification or when testing the samples. Here, we present approaches for suitability verification and the scientific rationale supporting compendial methods: visible particulates, subvisible particles, pH, osmolality, color and clarity/opalescence. Current challenges and recommendations are also discussed specifically for the analysis of protein products.