Module 9 2024

03/09/2024

Bioassay Validation Guidance

• ICH Q2(R2): Validation of analytical procedures: Text and methodology

• U.S. Pharmacopeia (USP) 1033: Biological Assay Validation

• FDA Analytical Procedures and Methods Validations for Drugs and Biologics

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Bioassay Validation

Include stability indicating samples

Rehder, et al Biochemistry 2008, 47, 2518-2530

Monoclonal antibody • Decreased in vitro potency when stored under certain conditions • Not due to aggregation or proteolysis, no change in MW • RP-HPLC: increased peak preceding light chain peak, both same MW • Peptide maps: additional peptide, same MW as control • Sequence analysis + Asp-N enzymatic digestion: early eluting peptide has isomerization of Asp 92 • Potency decreases with increase in iso-Asp at position 92

The Organisation for Professionals in Regulatory Affairs

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