Post-approval Changes – Stability Requirements and Regulations

  • Frank J. DianaEmail author


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 The 1987 stability guideline and the 1998 draft stability guideline (withdrawn in 2006) provide a good background on FDA thinking with regard to stability requirements for post-approval changes.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.


Dosage Form Active Pharmaceutical Ingredient Expiration Date Stability Requirement Site Change 
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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Endo PharmaceuticalsChadds FordUSA

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