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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

Abstract

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.

Keywords

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

Abbreviations

AC

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

DS

Drug substance

DP

Drug product

HT/HH

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

ICH

International Conference on Harmonisation

GLP

Good laboratory practice

GMP

Good manufacturing practice

LT

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

LT/AC

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

PFOS

Powder for oral solution

RH

Relative humidity

Notes

Acknowledgments

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.

References

  1. 1.
    ICH Q1A(R2) stability testing of new drug substances and productsGoogle Scholar
  2. 2.
    ICH Q1B stability testing: photostability testing of new drug substances and productsGoogle Scholar
  3. 3.
    ICH Q1D bracketing and matrixing designs for stability testing of new drug substances and productsGoogle Scholar
  4. 4.
    ICH Q1E stability dataGoogle Scholar
  5. 5.
    WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-third report. Geneva, World Health Organization, 2009, Annex 2 (WHO Technical Report Series, No. 953)Google Scholar
  6. 6.
    Beaman JV. “Stability testing: doing everything or doing the right thing?” Pharm. Rev. July/August 2010.Google Scholar
  7. 7.
    US FDA Guidance for industry content and format of investigational new drug applications (INDs) for phase 1 studies of drugs, including well-characterized, therapeutic biotechnology-derived products, November 1995Google Scholar
  8. 8.
    EMA: guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials—CHMP/QWP/185401/2004 FinalGoogle Scholar
  9. 9.
    Waterman KC, Carella AJ, Gumkowski MJ, Lukulay P, Macdonald BC, Roy MC, et al. Improved protocol and data analysis for accelerated shelf-life estimation of solid dosage forms. Pharm Res. 2007;24(4):780–90.PubMedCrossRefGoogle Scholar
  10. 10.
    Waterman KC and Colgan ST. A science-based approach to setting expiry dating for solid drug products. Regulatory Rapporteur. 2008;5(7):9–14.Google Scholar
  11. 11.
    Colgan ST, Whipple RD, Watson TJ, Nosal R, Beaman JV and DeAntonis DM. “The application of quality by design’s science and risk based concepts to API stability strategies.” AAPS Stability Workshop, September 2009. Google Scholar
  12. 12.
    Colgan ST, Watson TJ, Whipple RD, Nosal R, Beaman JV, De Antonis DM. “The application of science and risk based concepts to drug substance stability strategies.” J. Pharm. Innov. (JPI). doi: 10.1007/s12247-012-9135-9.
  13. 13.
    ICH Q3A(R2) impurities in new drug substancesGoogle Scholar
  14. 14.
    ICH Q3B(R2): Impurities in new drug productsGoogle Scholar
  15. 15.
    US Pharmacopoeia (USP) 34-National Formulary (NF) 29 S1, general chapter <1150> pharmaceutical stability.Google Scholar
  16. 16.
    Qiu F, Cohen K. “Control of genotoxic impurities in pharmaceutical products.” Chapter 63 in encyclopedia of pharmaceutical science and technology (4th edn), volume 1, Informa Healthcare.Google Scholar

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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