One Set of Specifications?
“A globally harmonized regulatory approach for specifications of well-characterized biological products would be desirable for both pharmaceutical manufacturers and regulatory authorities,“ states Laura Bass, Ph.D., of Pfizer (www.pfizer.com). Currently, for a given product marketed worldwide there may be differences in requirements for tests, analytical procedures, and/or acceptance criteria between regulatory regions. This makes development of a global set of specifications an extremely challenging task.
Whereas the ideal scenario, according to Amy Dingley of Stryker Biotech (www.stryker.com), would be a single international specification for raw materials and intermediates, process control, release, and expiry, the real-world situation is more challenging.
Differing compendial requirements for raw materials, differing requirements for in-process and release specifications, and a staggered approach to registration can result in a plethora of registration rules for a single product. Stryker’s strategy is to maximize the product similarities at the upstream end, pushing the differences further downstream to gain flexibility.
The process of setting specifications for a biologic suffers from varying interpretations by regulatory bodies, making global harmonization a distant goal rather than an immediate possibility, states Wassim Nashabeh, Ph.D., of the department of analytical chemistry at Genentech (www.genentech.com).
Dr. Nashabeh proposes an integrated lifecycle approach through all phases of product development. Key features of the lifecycle strategy include the characterization of clinical and nonclinical attributes specifying the clinical relevance and clinical ranges. In addition, the process capability and manufacturing consistency need to be taken into account.
The characterization of biologics is progressing rapidly, thanks to advances in instrumentation and the expanding ability of scientists to detect finer levels of divergence among products. However, advances in the laboratory will have to be matched by standardization of international regulatory guidelines if the worldwide sharing and marketing of biologicals is to move forward expeditiously.