In a study released in May 2011, US regulatory approvals for biologic drugs and biotechnology products (collectively referred
to as "biologics") were reported to have nearly doubled in the past decade, compared with the 1990s. This growing market emphasizes
the need for consistent approaches to product quality and public standards. In its upcoming Science & Standards Symposium
on Biologics & Biotechnology, "Advancing Quality Standards through Analytics and Assays," taking place October 3-6 in Seattle,
the US Pharmacopeial Convention (USP) will lead discussions on standards-setting initiatives related to biologics and the
materials critical for their manufacture as a growing number of these types of drugs enter the therapeutic space.
Setting the stage for the symposium are keynote speakers Steve Kozlowski, director of the FDA Office of Biotechnology Products,
and Gillian Woollett, chief scientist at the Washington, DC, law firm Engel & Novitt. Each will discuss the regulation of
biologics. The following two-and-a-half days of technical sessions will include presentations from an international panel
of industrial, academic, and regulatory stakeholders engaged in the development of quality standards for biologics. USP topic
experts will discuss general analytical approaches and what they can do for biologics; quality attributes of biologic drugs
by product class; and the US regulatory landscape for these products. An entire track of sessions will focus on bioassays
and the assessment of biological potency, critical to all biological medicines.
New approach for biologics standards
Quality standards set by the USP—and enforceable by FDA—have traditionally been developed using what's called a "vertical
approach," which is particularly suited for the characterization of small-molecule drugs. Under this approach, documentary
standards (or product monographs) have been created for one drug product at a time, with associated reference materials (i.e.,
pure physical samples used as reference chemicals for testing) developed in tandem with monographs. General chapters in USP's
official compendium, US Pharmacopeia-National Formulary (USP-NF), represent overarching information and testing procedures that apply across all or groups of monographs. These chapters broadly
support product-specific (vertical) standards in the determination of identity, strength, and purity.
Compared with their small-molecule counterparts, biologics are heterogeneous and more complex in their makeup. Thus, analysis
and characterization are more challenging and require an even greater portfolio of good analytical procedures that can underpin
product characterization. Another important issue for biologics quality is the use of ancillary and process materials that
are also complex biologics. Common examples are fetal bovine serum (FBS) widely used in vaccine manufacturing; cytokines like
interleukin-4 (IL-4) used in the cell-therapy arena; and materials like protein A, used in monoclonal-antibody manufacturing.
The quality of these materials going into the manufacturing process can have a direct impact on the quality of the medicinal
product itself, especially when the end product is not highly purified and residual amounts of the ancillary material have
Working through expert committees and advisory expert panels, the USP biologics and biotechnology department has been actively
revising and developing new chapters in USP-NF. Work has focused on general guidance in the form of information chapters, and also on specific test and product-class chapters
that speak to the analysis of quality attributes for certain biologics product classes and the analytical procedures necessary
to measure them. The goal with these "horizontal" standards is to provide more broadly applicable quality expectations in
areas where analytical platform approaches already exist.