, , , , , ,

By Feroz Jameel, Susan Hershenson, Mansoor A. Khan, and Sheryl Martin-Moe

Feroz Jameel-finalSusan Hershenson-finalMansoor Khan-finalSheryl Martin-Moe-finalWhat does implementation of a quality by design (QbD) approach mean for development and manufacturing of biologic drugs? A new paradigm for drug development based on enhanced science and risk-based pharmaceutical quality assessment, QbD started with the 2002 publication of the FDA initiative Pharmaceutical cGMPs for the 21st Century and was further expanded in ICH Q8, 9, and 10 guidance documents. The pharmaceutical industry has struggled with interpretation and implementation of QbD ever since.

In 2008, the FDA Office of Biological Products QbD pilot program began. This was followed by 2009 publication of “A-Mab: A Case Study in Bioprocess Development” by the CMC Biotech Working Group industry/FDA consortium in an effort to help define a development path using QbD. Overall, the industry response to adopting QbD for biologic development has been mixed, with concerns expressed about cost and benefit. In response, many companies have taken a wait and see attitude to QbD, while others have incorporated QbD elements into development programs and a few have actively pursued QbD submissions for design space. To date, FDA “QbD design space” biologic approvals include an expanded change protocol for a drug substance transfer in 2010, and a new biologic (Gazyva) with design space in 2013 (both Genentech).

In a closer look, however, quality by design practices have already added significant value to developing biologic processes and to a deeper understanding of manufacturing processes. Improvements in development in a short time are quite remarkable and include: improved communication of standardized elements used to describe the process across departments, sites, companies and the industry, an enhanced ability to differentiate criticality, and a process to define testing logic and mechanisms to increase process knowledge.

In the new book Quality by Design for Biopharmaceutical Drug Product Development, we can see that the foundation for success of quality by design for biologics is in place, with concrete examples of implementation and feedback from regulators and the FDA QbD pilot program. QbD is applied to formulation development, drug product processes, inspection and shipping and handling, primary containers, devices, combination product development, technology transfer, and lifecycle management. Examples will help to catalyze further development and broader application of the QbD methodology with gains in terms of greater process knowledge, more rapid development, and greater ease of implementing changes within a well-defined design space. Biologics drug product is particularly well suited for the application of quality by design principles and approaches, both in terms of the relative ease of application and the potential benefits to the industry.

Feroz Jameel, Ph.D., is a principal scientist for Parenteral Product & Process Development at Amgen Inc, where he is involved in product and process development, optimization, scale-up and transfer to manufacturing of biopharmaceuticals.
Susan Hershenson, Ph.D., is deputy director of Chemistry, Manufacturing and Controls at the Bill and Melinda Gates Foundation, where her major responsibilities are to support CMC development and drug delivery needs for therapeutic projects funded by the foundation.
Mansoor A. Khan, Ph.D., is director of Product Quality Research and a senior biomedical research scientist at CDER in FDA, where he overseas research teams on biotech products, chemistry and stability, drug delivery systems, and bioavailability/bioequivalence.
Sheryl Martin-Moe, Ph.D., is executive vice president, Pharmaceuticals and Combination Products, at Enterprise Catalyst Group, where she consults for the pharmaceutical industry, specializing in development and commercialization of pharmaceuticals and combination products.