While the design of clinical and pre-clinical studies absorbs considerable attention in the biomedical research world, manufacturing science has emerged as a critical element in moving products from clinical testing to commercial scale-up. Ensuring access to consistently high-quality biotech therapies, vaccines, and blood products is the focus of efforts by the Center for Biological Evaluation and Research (CBER) to spur new product development. This topic was explored at a CBER workshop last October (2004) on opportunities for collaboration with industry and other stakeholders under FDA's "Critical Path" initiative.
MORE ASSISTANCE To ensure that early studies will lead to quality products, CBER officials are emphasizing the value of discussing critical manufacturing issues with sponsors early in the clinical development process. CBER's Office of Compliance and Biologics Quality (OCBQ), now headed by Mary Anne Malarkey, is encouraging this approach, especially for companies considering novel methods for scale-up, product sampling, manufacturing process control, or compliance with good manufacturing practices (GMPs). Meetings to address topics such as appropriate containers and shipping is particularly critical for cellular and gene therapies. Despite ever-tightening resources, OCBQ is offering decision-making assistance on raw material selection, sampling techniques, product shipping, technology transfer, manufacturing scale-up and automation, and other key activities.
At the Food and Drug Law Institute (FDLI) annual meeting in April, CBER director Jesse Goodman described continuing efforts to gain manufacturer input in setting priorities for cross-cutting collaborative research that could develop:
MODERNIZING SPECIFICATIONS Efforts to ensure the quality of biotech products also derive from FDA's GMP modernization campaign. While biotech manufacturers have incorporated many elements of a more risk-based oversight system into operations, the search continues for new ways to ensure product quality.
One current initiative seeks to help manufacturers adapt marketed products to meet changing needs and technological advances by setting more appropriate product specifications and limits. The current system has been criticized for relying on end-product testing to ensure that production batches are similar to batches tested in the clinic. This approach, though, fails to explain the relationship between specifications and desired clinical outcomes. Product specifications often are too wide, too tight, overly rigid, or irrelevant to clinical performance and thus frequently lead to excessive out-of-specification results that can be very costly.