Institution: | 1. Biopharmaceutical Product Sciences, GlaxoSmithKline R&D, 709 Swedeland Road, King of Prussia, Pennsylvania 19406;2. Drug Product Science and Technology, Bristol-Myers Squibb, One Squibb Drive, New Brunswick, New Jersey 08903;3. Pharmaceutical Development & Supplies, PTD Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland;4. Biologics Preformulation and Drug Product Development, Abbvie Bioresearch Center, Worcester, Massachusetts 01605;5. Shire Pharmaceuticals, Industriestr 72, Vienna 1221, Austria;6. Merck & Co., Inc., Biologics and Vaccines Development, 2000 Galloping Hill Road, Kenilworth, New Jersey 07033;7. Formulation Development, Takeda Pharmaceuticals International Co., 40 Landsdowne Street, Cambridge, Massachusetts 02139;8. Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, New York 10591;9. Protein Pharmaceutical Development. Biogen, 14 Cambridge Center, Cambridge, Massachusetts 02142;10. Analytical & Pharmaceutical Sciences, ImmunoGen, Inc., 830 Winter Street, Waltham, Massachusetts 02145;11. Shire, 300 Shire Way, Lexington, Massachusetts 02421;12. Pharmaceutical Development, Alexion Pharmaceuticals Inc., 100 College Street, New Haven, Connecticut 06510;13. BioPhorum Operations Group, Sharrow Vale Road, Sheffield, S11 8YZ, UK |
Abstract: | The Biophorum Development Group (BPDG) is an industry-wide consortium enabling networking and sharing of best practices for the development of biopharmaceuticals. To gain a better understanding of current industry approaches for establishing biopharmaceutical drug product (DP) robustness, the BPDG-Formulation Point Share group conducted an intercompany collaboration exercise, which included a bench-marking survey and extensive group discussions around the scope, design, and execution of robustness studies. The results of this industry collaboration revealed several key common themes: (1) overall DP robustness is defined by both the formulation and the manufacturing process robustness; (2) robustness integrates the principles of quality by design (QbD); (3) DP robustness is an important factor in setting critical quality attribute control strategies and commercial specifications; (4) most companies employ robustness studies, along with prior knowledge, risk assessments, and statistics, to develop the DP design space; (5) studies are tailored to commercial development needs and the practices of each company. Three case studies further illustrate how a robustness study design for a biopharmaceutical DP balances experimental complexity, statistical power, scientific understanding, and risk assessment to provide the desired product and process knowledge. The BPDG-Formulation Point Share discusses identified industry challenges with regard to biopharmaceutical DP robustness and presents some recommendations for best practices. |