Post-Approval Changes for Large Scale Biopharmaceutical Manufacturing: Global
Growing global demand for life saving products produced by large-scale biopharmaceutical manufacturing processes dictates that changes to the process, the facilities, the equipment, and/or the analytical controls used to produce them be expeditiously implemented without adverse impact on product quality. The implementation of significant post-approval manufacturing changes is governed by applicable government regulations that can vary dramatically from market to market. In today’s rapidly evolving regulatory environment, manufacturers of large-scale biopharmaceuticals face unprecedented global challenges in meeting post approval regulatory requirements and, at the same time, ensuring an uninterrupted supply of safe and efficacious product to the patient. Grounded in the concept of product comparability, this chapter shall endeavor to develop an understanding of the intricacies of the global post-approval regulatory environment. A series of case studies will be utilized to illustrate these complexities.
About the Authors
John J. Dougherty, Regulatory Research Scientist, Eli Lilly and Company
Mr. Dougherty is responsible for post-approval regulatory support for a number of recombinant protein active pharmaceutical ingredients (APIs). He has been employed by Eli Lilly for 11 of his 20 years in the industry; previous employers include Tektagen, Inc., and The Upjohn Company. Mr. Dougherty received his AB degree from Dartmouth College in 1979 majoring in chemistry and his MS degree in biochemistry from the University of Illinois, Urbana-Champaign in 1983. He is a member of both the Regulatory Affairs Professionals Society and the California Separation Science Society. John is currently serving as an industry co-chairman for the WCBP 2004 symposium and as a member of the advisory committee of the WCBP CMC Strategy Forum. Mr. Dougherty is also a member of the Editorial Advisory and Peer Review Board for Bioprocess International. He has lectured extensively and published several articles on peptide mapping and other analytical issues related to biotechnology.
James W. Precup, Ph.D., Regulatory Scientist, Indianapolis Site Regulatory Affairs, Eli Lilly and Company
Dr. Precup has seven years post-approval regulatory experience with biologic products (human coagulation factors/plasma proteins), and biotechnology - E.coli derived drug substances. Prior to his assignments in regulatory affairs, Dr. Precup was Manager of Technical Operations responsible for production support and process improvement of plasma derived coagulation factors. Dr. Precup received a B.S. and M.S. degrees in Biology from the University of Illinois, Urbana, and a Ph.D. degree in Microbiology/Molecular Biology from Southern Illinois University.
Josephine Secnik, M.S., MBA, Regulatory Scientist, Indianapolis Site Regulatory Affairs, Eli Lilly and Company
Ms. Secnik is has 4 years of experience in CMC Regulatory Affairs, with responsibilities for pre- and post-approval CMC regulatory submissions. Prior to her assignment in Regulatory Affairs, Ms. Secnik was a Quality Assurance Consultant with responsibilities for early and late stage biopharmaceutical development projects (1998-2002). Ms. Secnik was previously Senior Financial Analyst for Bioproducts (1995-1997) and Senior Associate Biochemist with responsibilities for purification process development and pilot-scale manufacturing of clinical trial material (1990-1995). Ms. Secnik received a B.A. and M.S. degree in Biochemistry from Case Western Reserve University, Cleveland, OH in 1987 and 1990 and an MBA degree in Finance from Indiana University, Bloomington, IN in 1995.
John Towns, Director, Global Regulatory Affairs, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN
Dr. John Towns is Director, Global CMC Regulatory Affairs at Eli Lilly and Company. Dr. Towns has both pre-approval and post-approval global CMC regulatory affairs responsibilities for Lilly’s portfolio of chemically synthesized and biotechnology-derived drug substances and drug products, including the regulatory activities at the 15 manufacturing sites around the world. Prior to his assignment in regulatory affairs, Dr. Towns was Head of Biopharmaceutical Technology Development with responsibilities for early and late stage biopharmaceutical development projects (1994-1999). Dr. Towns was previously Senior Analytical Chemist with responsibilities for line extension development and product technology advancement for recombinant protein products (1991-1994). Dr. Towns received a BS degree in Chemistry from California Polytechnic State University, San Luis Obispo, California in 1986 and a Ph.D. degree in Analytical Chemistry from Purdue University, West Lafayette, Indiana in 1991.