Revision of USP Chapter <1033> on Validation of Biological Assays published

The USP had already published an initial proposal for the revision of Chapter <1033> on the validation of biological assays at the end of 2022 and beginning of 2023. However, this was rejected so that the current revision proposal is again based on the official version published in 2013.  Bioassays play an essential role in the qualitative assessment in the production and release process. They also differ significantly from chemical tests as they are based on biological systems such as animals, cells, functional target receptors or immunological reagents. This leads to a significantly higher variability than with chemical tests. Therefore, this general USP chapter focuses on validation approaches that allow flexible adaptation to new bioassay technologies, new biological products or both.

Changes and adjustments

Regarding content, the proposal of the USP statistics expert group lists the following changes and adjustments in the overview:

1. Moving the validation example to Annex A and consolidating the current Annexes into sections of the main text by:

• Adding a subsection 3.3 Linearity
• Adding a subsection 3.5 Overall analytical error
• Adding a detailed description of mixed effects modeling of validation results

2. Clarifying the distinction between bioassay methods and procedures by:

• Making the design and development of bioassay methods the subject of two new chapters, "Design and Development of Biological Assays <1032>" and "Analysis of Biological Assays <1034>", which will appear in a forthcoming issue of PF
• Using validation results to develop methods to answer important biological questions such as product release

3. Correcting validation errors by:

• Allowing justification of bioassay format changes to meet precision requirements for a reportable value
• Using the TAE as a primary or secondary validation criterion when individual parameter criteria are not met, provided the TAE is acceptable

4. Elimination of inconsistencies with the International Council for Harmonization ICH Q2(R2) Guideline on Validation of Analytical Procedures:

• Considering repeatability (intra-run variability) as a component of overall variability (inter-run precision)

The current Chapter also refers to other Chapters and Guidelines that play a role in validation under GMP requirements, e.g. "Validation of Compendial Procedures <1225>", which describes assay validation parameters or <1220> on the life cycle or the Bioassay Overview Chapter <1030>.

The complete revision proposal can be viewed on the USP website after registration.

In this context, please note the new conference on Bioassays/Potency Assays at the PharmaLab Congress 2024.