Unique Challenges of Quality by Design (QbD) for Biotechnology Products: Lessons Learned from the OBP QbD Pilot Program
The implementation of QbD requires extensive information about the product and its manufacturing process. This represents a significant challenge for biotechnology products due to their functional and structural complexity and the complexity of their manufacturing processes. It is not possible to directly evaluate the impact every quality attribute has on safety and efficacy nor is it possible to evaluate the impact of each process parameter on each quality attribute. Biotechnology manufactures, therefore, must rely on risk management tools and statistical approaches (such as design of experiments and multi-variate analysis) to focus efforts on the most relevant areas needed to support implementation of QbD for their products. On July 2, 2008 the Office of Biotechnology Product (OBP) published a Federal Register notice on their quality by design (QbD) pilot program. The program was designed to define clinically relevant attributes for protein products regulated by OBP and link them to manufacturing processes. The program considered QbD approaches to unit operations in supplements as well as original biologic license applications (BLA). It was also intended to explore the use of expanded change protocols submitted under 21 CFR 314.70(e) and 601.12(e). Dr. Rellahan will summarize key findings from the pilot program meetings and applications submitted after inclusion in the program.