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Considerations for Updates to ICH Q1 and Q5C Stability Guidelines: Embracing Current Technology and Risk Assessment Strategies

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A Correction to this article was published on 15 November 2021

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Abstract

In consideration of the recent ICH Quality Discussion Group (QDG) recommended revision to the ICH series of stability guidelines, the IQ Consortium (International Consortium for Innovation and Quality in Pharmaceutical Development) Science- and Risk-based Stability Working Group conducted a comprehensive review of ICH Q1A, Q1B, Q1C, Q1D, Q1E, and Q5C to identify areas where the guidelines could be clarified, updated, and amended to reflect the potential knowledge gained from current risk-based predictive stability tools and to consider other science- and risk-based stability strategies in accordance with ICH Q8–12. The recommendations propose a holistic approach to stability understanding, utilizing historical data, prior knowledge, modeling, and a risk assessment process to expand the concept of what could be included (or would be acceptable) in the core stability data package, including type and amount of stability evidence, assignment of retest period and shelf-life for a new product, and assessment of the impact of post-approval changes.

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Acknowledgements

The authors would like to thank the following colleagues for the thoughtful review comments they provided on this paper: Jin Wang, Chait Wannere, Barbara Rellahan, Beth Kendsersky, Kevin Ryan, Ron Ogilvie, Clarice Hutchens, Mark D. Argentine, Michael R. De Felippis, George Daniel Willingmyre, Siqing Song, Kelly Norton, Cheryl Pape, Paul Hermes, Carolyn Gordon, Anette Skoog, Richard Bradley, Angelica Wickström, Simon Lee, Timothy Watson, and Margaret Faul.

The authors wish to dedicate this article to Helen Williams, who passed away in August 2021 after a long illness.  Helen was a founding member of the IQ Working Group for Risk Based Predictive Stability and played a fundamental role in the success and growth of the group, building connections and authoring several publications.  As a leader and advocate for the emerging field of predictive stability, Helen championed the acceleration of pharmaceutical development and brought energy and determination to the task of reinventing established practice.  Helen was a wonderful friend and colleague, and will be profoundly missed by the pharmaceutical stability community.

Funding

Not applicable; authors contributed case studies based on existing company knowledge and experience.

Author information

Authors and Affiliations

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

    Megan E. McMahon & Robert Timpano

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

    Alexander Abbott

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

    Yelizaveta Babayan, Cherokee Hoaglund-Hyzer & Chad Wolfe

  4. Takeda Pharmaceuticals Inc., 40 Landsdowne Street, Cambridge, Massachusetts, 02139, USA

    Jenny Carhart

  5. Pfizer Inc. (Retired), 8455 Colesville Rd, Silver Spring, Maryland, 20910, USA

    Chi-wan Chen

  6. Janssen R&D A Division of Janssen Pharmaceutica NV, Turnhoutseweg 302340, Beerse, Belgium

    Elke Debie

  7. Sunovion Pharmaceutical Inc., 84 Waterford Drive, Marlborough, Massachusetts, 01752, USA

    Mingkun Fu

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

    Andrew Lennard

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

    Hanlin Li

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

    Tony Mazzeo

  11. Seagen Inc., 21823 30th Drive SE, Bothell, Washington, 98021, USA

    Lori McCaig

  12. GlaxoSmithKline, Great West Road, Brentford, TW8 9GS, Middlesex, UK

    Sylvine Pischel

  13. Boehringer Ingelheim, 900 Ridgebury Road, Ridgefield, Connecticut, 06877, USA

    Fenghe Qiu

  14. AbbVie, 1 N Waukegan Road, North Chicago, Illinois, 60064, USA

    Dennis Stephens & Debra Webb

  15. 225 Binney Street, Cambridge, MA, 02142, USA

    Kayla Woodlief

  16. Merck & Co., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA

    Yan Wu

Authors
  1. Megan E. McMahon
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  2. Alexander Abbott
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  3. Yelizaveta Babayan
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  4. Jenny Carhart
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  5. Chi-wan Chen
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  6. Elke Debie
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  7. Mingkun Fu
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  8. Cherokee Hoaglund-Hyzer
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  9. Andrew Lennard
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  10. Hanlin Li
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  11. Tony Mazzeo
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  16. Robert Timpano
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  17. Debra Webb
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  18. Chad Wolfe
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  19. Kayla Woodlief
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  20. Yan Wu
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Contributions

All authors contributed to the conception and design of this manuscript and the detailed recommendations listed in the supplementary material. Chi-wan Chen authored the “Introduction” section. Alexander Abbott, Andrew Lennard, Lori McCaig, Jenny Carhart, Robert Timpano, Fenghe Qiu, Dennis Stephens, Hanlin Li, Megan McMahon, and Chi-wan Chen authored the “Recommendations” section. Lori McCaig authored the “Discussion” section. Megan McMahon authored the “Conclusion” section. All authors reviewed, edited, and approved the manuscript.

Corresponding author

Correspondence to Megan E. McMahon.

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The authors declare no competing interests.

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The original online version of this article was revised to add the graphical abstract.

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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McMahon, M.E., Abbott, A., Babayan, Y. et al. Considerations for Updates to ICH Q1 and Q5C Stability Guidelines: Embracing Current Technology and Risk Assessment Strategies. AAPS J 23, 107 (2021). https://doi.org/10.1208/s12248-021-00641-6

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