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Science- and Risk-Based Stability Strategies to Support Product Lifecycle Changes

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Abstract

ICH Q12 asserts that science- and risk-based approaches are applicable to stability studies supporting Chemistry, Manufacturing and Controls (CMC) post-approval changes (PAC) to enable more timely implementation; however, no guidance or specific examples are provided to demonstrate how prior knowledge of the product can inform the risk assessment for the proposed change(s). Ten diverse case studies are presented in this manuscript to demonstrate how science- and risk-based stability strategies were used to support drug substance and product CMC PAC and lifecycle management activities. The accumulated stability knowledge held by original manufacturers of marketed products is substantial, and different elements of this knowledge base were used to assess the risks and impact of the proposed changes for confident change management. This paper provides ways to leverage science- and risk-based stability strategies as part of the post-approval change-management risk-mitigation strategy, which may enable a reduced stability data commitment and/or a reduced reporting category for change implementation.

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Acknowledgements

The authors would like to thank Haiyan Grady, Rusty Hertzler, Debra Webb, Shyamala Jayaraman, Karen Sitney, Sebastian Koenig, Ron Ogilvie, Olivier Dirat, Timothy Graul, Paul Gerst, Jonathan Beaman, Joann Parker, Deanna Hurum, Sarina Ma, Eric Gorman, Hong Long, Judy Ostovic, Melissa Morrison, Tiffany Pham, Nora Chew, Anette Skoog, Angelica Wickström, Carolyn Gordon, Greg Carr, Pamela Harrison, Richard Bradley, and Sean Cunningham for their constructive feedback and thoughtful recommendations during their review of this manuscript.

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Authors and Affiliations

  1. Pfizer Inc, 21823 30Th Drive SE, Bothell, Washington, 98021, USA

    Lori McCaig

  2. AbbVie, 1 N Waukegan Rd. Bldg. AP50; Dept PA71, North Chicago, Illinois, 60064, USA

    Steven Nowak

  3. Oral Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Silk Road Business Park, Macclesfield, Cheshire, SK10 2NA, UK

    Alexander Abbott

  4. Takeda Development Center Americas, Inc. 95 Hayden Ave, Lexington, Massachusetts, 02421, USA

    Jenny Carhart

  5. Pfizer Inc, Eastern Point Road, Groton, Connecticut, 06340, USA

    Megan E. McMahon & Robert Timpano

  6. Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340, Beerse, Belgium

    Elke Debie

  7. Vertex Pharmaceuticals, 50 Northern Avenue, Boston, Massachusetts, 02210, USA

    Hanlin Li

  8. AbbVie, 1401 Sheridan Road, North Chicago, Illinois, 60064, USA

    Francis Maina

  9. Genentech Inc, 1 DNA Way, South San Francisco, California, 94080, USA

    Andrea J. Ji

  10. Sumitomo Pharma America, 84 Waterford Drive, Marlborough, Massachusetts, 01752, USA

    Mingkun Fu

  11. Merck & Co, 2000 Galloping Hill Road, Kenilworth, New Jersey, 07033, USA

    Yan Wu

  12. Amgen Ltd, 4, Uxbridge Business Park, Sanderson Road, Uxbridge, UB8 1DH, UK

    Andrew Lennard

  13. Bristol Myers Squibb, 1 Squibb Drive, New Brunswick, New Jersey, 08903, USA

    Tony Mazzeo

  14. Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana, 46285, USA

    Chad Wolfe & Yelizaveta Babayan

  15. CSL Behring, CSL Behring AG, Wankdorfstrasse 10, CH-3014, Bern, Switzerland

    Lars Gruenig

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  1. Lori McCaig
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Contributions

All authors contributed to the conceptualization, design, case studies, critical review, and approval of this manuscript. Lori McCaig authored the “Introduction” section, Megan McMahon authored the “Regulatory History” section, Steven Nowak authored the Discussion section, and Steven Nowak and Lori McCaig authored the Conclusion.

Corresponding author

Correspondence to Steven Nowak.

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All authors declare that they are employees of their respective companies as listed in their affiliations at the top of this paper and as such all authors declare that they may have ownership, options and/or interests in the stock of their respective companies, if applicable. The authors declare no additional competing interests.

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This paper was developed with the support of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ, www.iqconsortium.org). IQ is a not-for-profit organization of pharmaceutical and biotechnology companies with a mission of advancing science and technology to augment the capability of member companies to develop transformational solutions that benefit patients, regulators, and the broader research and development community.

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McCaig, L., Nowak, S., Abbott, A. et al. Science- and Risk-Based Stability Strategies to Support Product Lifecycle Changes. AAPS J 26, 34 (2024). https://doi.org/10.1208/s12248-024-00903-z

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