Advertisement

Post-approval Changes – Stability Requirements and Regulations

  • Frank J. Diana

Abstract

There are many reasons for making changes to pharmaceutical products after the original regulatory approval is obtained. Some of these changes may be significant and require a substantial amount of stability data while others are minor and may only require a stability commitment. Company change control procedures should detail how changes are evaluated and implemented as well as how the change impacts stability and what data will be needed to support the change. The regulatory group will determine the strategy for submission based on a review of the technical assessment of the change and the appropriate regulatory guidance. The strategy may be more complex if the product is marketed globally. The stability requirements will typically be assessed by a team led by the stability group and including quality assurance (QA), technical and regulatory affairs. Once agreed upon, this information will be captured in a stability protocol and reviewed/approved by the team. Based on the submission strategy, a stability report will be written for inclusion in the supplement, variation (for global changes) and/or the annual report.

In the US, the current regulations around changes are covered in 21CFR314.70 and indicate that “The applicant shall notify the FDA about each change in each condition established in an approved application beyond the variations already provided for in the application”. The 1987 stability guideline and the 1998 draft stability guideline (withdrawn in 2006) provide a good background on FDA thinking with regard to stability requirements for post-approval changes. The Scale Up and Post Approval Change Guidances (SUPAC) and the Changes to an Approved NDA or ANDA (issued in April, 2004) offer a significant amount of information to guide the sponsor in filing and data requirements [1–5]. Similarly, for global changes there are several guidances available to provide requirements for various types of changes [6–10]. Web sites and addresses are provided in the references section of this chapter for these guidances from FDA, European Medicines Agency (EMEA), Health Canada, and World Health Organization (WHO). International Conference on Harmonization (ICH) Guidelines can also be found on the FDA web site.

Keywords

Dosage Form Active Pharmaceutical Ingredient Expiration Date Stability Requirement Site Change 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    FDA/CDER (November 1995) Guidance for industry scale up and post-approval changes: immediate release solid oral dosage forms.Google Scholar
  2. 2.
    FDA/CDER (September 1997) Guidance for industry scale up and post-approval changes: modified release solid oral dosage forms.Google Scholar
  3. 3.
    FDA/CDER (May 1997) Guidance for industry scale up and post-approval changes: nonsterile semisolid dosage forms.Google Scholar
  4. 4.
    FDA/CDER (January 1999) Guidance for industry scale up and post-approval changes: immediate release and modified release solid oral dosage forms manufacturing equipment addendum.Google Scholar
  5. 5.
    FDA/CDER (April 2004) Guidance for industry changes to an approved NDA or ANDA.Google Scholar
  6. 6.
    CHMP/CVMP (December 2005) Guideline on stability testing for applications for variations to a marketing authorization CPMP/QWP/576/96 Rev1 EMEA/CVMP/373/04.Google Scholar
  7. 7.
    EMEA (2006) Guideline on dossier requirements for Type IA and IB notifications.Google Scholar
  8. 8.
    WHO (2007) stability testing of active pharmaceutical ingredients and pharmaceutical products, draft – working document QAS/06.179/Rev.2.Google Scholar
  9. 9.
    WHO (February 2007) Annex 6 variations guidance: guidance on variations to a prequalified product dossier.Google Scholar
  10. 10.
    Health Canada (February 2007) Draft guidance document post-notice of compliance changes: quality document.Google Scholar
  11. 11.
    Carstensen JT (1993) Pharmaceutical principles of solid dosage forms. Technomic Publishing Co, Inc, Lancaster, PA, pp. 105–129.Google Scholar
  12. 12.
    United States Pharmacopeia 30th rev <661> Containers. pp. 272–286.Google Scholar
  13. 13.
    International Conference on Harmonization (ICH) (August 2001) Guideline Q7A Good manufacturing practice guidance for active pharmaceutical ingredients.Google Scholar
  14. 14.
    FDA/CDER (February 2003) Draft guidance for industry comparability protocols – chemistry, manufacturing and controls information.Google Scholar
  15. 15.
    FDA (September, 2004) Pharmaceutical cGMPs for the 21st century – a risk-based approach, final report.Google Scholar
  16. 16.
    International Conference on Harmonization (ICH) (May 2006) Guideline Q8, pharmaceutical development.Google Scholar
  17. 17.
    International Conference on Harmonization (ICH) (June 2006) Guideline Q9, quality risk management.Google Scholar
  18. 18.
    FDA/CDER (September 2004) Guidance for industry PAT – a framework for innovative pharmaceutical development, manufacturing, and quality assurance.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Endo PharmaceuticalsChadds FordUSA

Personalised recommendations