Industry Input Needed on Bioassay Standards

As an increasing number of biologics aim to enter the marketplace, US Pharmacopeial Convention (USP) is advancing efforts to develop guidance and tools for manufacturers and regulators to use in evaluating bioassays. Several new and revised general chapters in the US Pharmacopeia–National Formulary (USP–NF) compendia are being introduced this summer, and USP is seeking broad industry input as these standards are finalized.

GENERAL GUIDANCE CHAPTER SUITE PUBLISHED

Developing a comprehensive suite of bioassay guidance chapters has stemmed from revisions of USP's core compendial bioassay standard, General Chapter Design and Analysis of Biological Assays <111>. The revision was necessitated by rapid progress in computational analysis, assay design tools, and statistical understanding. Key issues addressed in the revision include: evaluating curve similarity, using equivalence testing as a statistical method in several areas of bioassay data analysis, and the best means for combining data from multiple assays.

Tina S. Morris, PhD

Initially published as a comprehensive revision of general chapter <111> in the March–April 2008 edition of USP's Pharmacopeial Forum (PF) 34(3), the proposal on bioassay analysis yielded pertinent public comment from a variety of stakeholders. Based on comments received and further consideration by a USP advisory panel, the next iteration of the proposal is in the proposed general chapter titled Analysis of Biological Assays <1034> that will be published in the July–August 2010 PF 36(4). It also will contain two related proposed general chapters: Validation of Biological Assays <1033> and Design of Biological Assays <1032>.

The chapters will be accompanied by a minor revision to the currently official <111>, to align this chapter with the new proposed chapters. A more comprehensive revision of <111> is planned after all product- and monograph-specific references in the chapter have been addressed. Eventually, all four chapters will be accompanied by a general chapter <1030> that will provide a roadmap, including a unifying glossary of terms. To solicit the most possible stakeholder input, USP is making the proposed chapters available for download and comment early on the USP web site. The public comment period ends October 15, 2010.

BIOASSAY TRANSITIONS AS A FOCAL POINT

USP expert committees continue to promote the replacement of animal-based bioassays in compendial standards, based both on ethical considerations regarding the use of animals and the fact that there is less variability in many cell-based or binding assays. To further advance discussion in this area, the second day of USP's 3rd Bioassay Workshop (www.usp.org/meetings/workshops/2010Bioassay.htm being held at USP's Rockville, MD, headquarters on August 11–12, will focus on transitioning bioassays. This discussion will follow a day of deliberations on implementing the USP general bioassay guidance.

FUNCTIONALITY OF ANCILLARY MATERIALS

Bioassays also play a key role in assessing ancillary materials that are of biological or biotechnology-derived origin. The USP Biologics and Biotechnology—Gene, Cell, and Tissue Therapies Expert committee has been actively working on new standards for ancillary materials that are widely used in biotechnology manufacturing. The most recent examples are Interleukin-4, used in cell therapy manufacturing, and fetal bovine serum, used in vaccine, cell, and gene therapy manufacturing. Both standards will include cell-line based bioassays as functionality tests. Bovine Serum Quality Attributes and Functionality Tests <90> and Cytokines used in Cell Therapy Manufacturing <92> are slated to become official in USP 34–NF 29, and associated reference standards currently are in development.

Tina S. Morris, PhD, is a vice president, biologics and biotechnology, US Pharmacopeial Convention (USP), Rockville, MD, 301.816.8397, tsm@usp.org