Biological Assay Validation



Recent revision intends to make changes based on feedback from stakeholders since the last revision of the chapter. The chapter was rearranged for better flow and readability.


A total error approach to OOS results is introduced with examples and additional references.


Biologicalassays (also called bioassays) are an integral part of the quality assessment required for the manufacturing and release of biological products. 


Biological products include biotherapeutics, vaccines, and cell and gene therapies. 


Bioassays are one of several methods with procedures and acceptance criteria that control critical quality attributes of a biological product. 


This chapter emphasizes validation approaches that provide flexibility to adapt to new bioassay methods, new biological products, or both.


GMPs require that test methods used for assessing compliance of pharmaceutical products with quality requirements should meet appropriate standards for accuracy and reliability. 


USP general chapter Validation of Compendial Procedures 〈1225〉 describes the assay performance characteristics (parameters) that should be evaluated for methods supporting small-molecule pharmaceuticals. 


This chapter addresses bioassay validation from the point of view of the measurement of potency rather than mass or other physicochemical properties, with the purpose of aligning bioassay performance characteristics with uses of bioassays in practice.


Assessment of bioassay performance is a lifecycle process (see Biological Assay Chapters—Overview and Glossary 〈1030>.


Bioassay validation is guided by a validation protocol describing the goals (validation parameters and acceptance criteria), design (sample selection and replication strategy), and analysis of results of the validation study.


This chapter addresses validation of relative potency (RP) bioassays. RP bioassays are based on a comparison of a concentration or dilution response profile for a test sample to that of a designated standard. 


Parameters that should be verified in bioassay validation are relative accuracy, specificity/selectivity, intermediate precision or IP (which incorporates repeatability), linearity, and range. 


A bioassay’s robustness be assessed as part of the method lifecycle. 


The robustness factors can be studied strategically by varying them simultaneously using a multifactorial approach (i.e., using design of experiments or DOE). 


While bioassay may be used for various investigations, this chapter will concentrate on its use in a release procedure.


The goal of the bioassay validation will be to assess accuracy and linearity, and to estimate both within-run and between-run variabilities of the method.

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