Journal of Pharmaceutical Innovation

, Volume 7, Issue 3–4, pp 214–224 | Cite as

Best Practices for Drug Substance Stress and Stability Studies During Early-Stage Development Part I—Conducting Drug Substance Solid Stress to Support Phase Ia Clinical Trials

  • Q. Chan LiEmail author
  • F. Qiu
  • K. Cohen
  • T. Tougas
  • J. Li
  • J. McCaffrey
  • T. Purdue
  • Jinhua J. Song
  • F. Swanek
  • S. Abelaira
Case Report


Regulatory guidances for drug stability testing during early development stages lack specifics. Consequently, companies either conduct more stability studies than necessary just to avoid regulatory questions or perform insufficient stability work resulting in regulatory questions and delays in drug development. Hence, there exist a pressing need and a great opportunity for pharmaceutical companies to share drug stability testing practices, rationales, and regulatory experiences for the early stages of development. This paper describes a quick, streamlined solid stress practice to support drug development from pre-clinical to Phase Ia Clinical Trials. By subjecting a few grams of drug substance to high temperature and high humidity (e.g., 70 °C/75 % RH, in open and closed containers, for three weeks) and to the ICH Q1B confirmatory photostability testing condition, the initial DS retest period and the initial shelf life of powder for oral solution can be reliably extrapolated, and a bulk packaging choice is made. In addition, the solid stress results can be used for multifaceted purposes. The solid stress practice offers a quick turnaround in obtaining adequate stability information for new drug development and achieves an optimum balance between risk and cost for Phase Ia clinical development.


Drug substance Powder for oral solution Early stage development Solid stress High temperature/high humidity Photostability Retest period Shelf life 



Accelerated storage condition (e.g., 40 °C/75 % RH)


Drug substance


Drug product


High temperature and high humidity (e.g., 70 °C/75 % RH)


International Conference on Harmonisation


Good laboratory practice


Good manufacturing practice


Long-term storage condition, e.g., 25 °C/60 % RH


Long-term storage condition/accelerated storage condition (25 °C/60 % RH/40 °C/75 % RH)


Powder for oral solution


Relative humidity



Special thanks go to Mr. Gordon Hansen, Drs. Chris Senanayake and Keith Horspool, and Ms. Patricia Watson for management support and to Ms. Cornelia Field, Dr. Christian Kulinna, and many BI colleagues for constructive discussions and contributions.


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Q. Chan Li
    • 1
    Email author
  • F. Qiu
    • 1
  • K. Cohen
    • 1
  • T. Tougas
    • 1
  • J. Li
    • 1
  • J. McCaffrey
    • 1
  • T. Purdue
    • 1
  • Jinhua J. Song
    • 1
  • F. Swanek
    • 1
  • S. Abelaira
    • 2
  1. 1.Development USBoehringer Ingelheim Pharmaceuticals, IncRidgefieldUSA
  2. 2.Boehringer Ingelheim, ArgentinaBuenos AiresArgentina

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