BRIEFING

 〈1033〉 Biological Assay Validation. This revision is based on the version of the chapter official prior to 2013. A previous proposal for this new chapter, published in PF 48(6) [Nov. 2022–Jan. 2023], has been canceled and is replaced by this updated proposal, which includes the following revisions by the Statistics Expert Committee:

1. Move the validation example to Appendix A and consolidate current appendices into sections of the main text by:

   • Adding a subsection, 3.3 Linearity

   • Adding a subsection, 3.5 Total Analytical Error

   • Adding a high level description of mixed effects modeling of validation results

2. Clarify the distinction between bioassay methods versus 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 an upcoming issue of PF

   • Using validation results to design and develop procedures for addressing key biological questions such as product release

3. Address the resolution of validation failures by:

   • Allowing for the justification of changes in bioassay format to satisfy the precision requirement on a reportable value

   • Employing the use of TAE as either the primary or secondary validation criterion when individual parameter criterion are not met, provided that the TAE is acceptable

4. Address inconsistencies with the International Council for Harmonisation guideline ICH Q2(R2)—Guideline on Validation of Analytical Procedures by:

   • Casting repeatability (within-run variability) as a component of overall variability (intermediate precision)

 Additionally, minor editorial changes have been made to update the chapter to current USP style.

 (GCSTAT: H. Tu)

 Case ID—SUB-151