FDA Goes into Detail About Generic Drug Stability Testing

| 14 May 2014 |  By 

A new guidance document released by the US Food and Drug Administration (FDA) aims to answer some common questions regarding stability testing used to support generic drug applications.


The guidance, ANDAs: Stability Testing of Drug Substances and Products: Questions and Answers, is a follow-up to a draft guidance released in September 2012, and then finalized in June 2013.

The stability studies are intended to ensure that a product maintains its potency, purity and overall integrity over time, such as the time it spends on a shelf awaiting use.

Under the latest guidance, FDA said it would look to standards set by the International Conference on Harmonisation (ICH), a group which counts the US, EU and Japan among its core membership.

Those guidelines are:

  • Q1A (R2) Stability Testing of New Drug Substances and Products.
  • Q1B Photostability Testing of New Drug Substances and Products.
  • Q1C Stability Testing for New Dosage Forms.
  • Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products.
  • Q1E Evaluation of Stability Data.

While those standards were developed with innovative-not generic-pharmaceuticals in mind, FDA said they are nevertheless applicable to products approved under an abbreviated new drug application (ANDA).

FDA's guidance lists seven recommendations on following the ICH standards:

  • Submit data from three pilot scale batches or two pilot scale batches and one small scale batch.
  • At the time of submission, provide 6 months of data that include accelerated and long-term conditions. FDA recommends following ICH guidelines with respect to utilization of intermediate conditions to support shelf-life.
  • Use multiple lots of drug substance as appropriate.
  • Manufacture and package the drug product using principles that are representative of the commercial process.
  • Provide a fully packaged primary batch.
  • Use drug product from all three primary batches when using bracketing and matrixing designs under ICH Q1D.
  • Provide statistical analysis of the data as appropriate, in accordance with ICH Q1E, Appendix A.

Final Q&A

But let's say FDA's guidance left you a bit confused and wanting more information. As it so happens, you're in luck.

FDA's latest Q&A guidance finalizes an earlier draft guidance by the same title released in August 2013 which clarified a bunch of specific-but nevertheless important-issues.

Some selected questions and answers are below:

When does FDA's stability guidance come into effect?20 June 2014
How does this affect ANDAs submitted under PEPFAR?There is a specific guidance document specific to HIV products which should be followed instead.
What happens if accelerated condition studies fail?The sponsor should submit intermediate stability study data
What's the maximum level of shelf life FDA will allow?Twice the available long-term data at the time of approval, or up to 24 months.
What about if a patent is about to expire-can a ANDA be filed with 3 months of stability data and a commitment to provide six in the future?No. Six months of stability data are required.
How long do pilot scale batches need to be stored before they can be destroyed?At least one year after the approval of an ANDA.
Should all batches be stored in the final proposed product packaging?Yes.
Should small-scale batches be packaged using commercial equipment?Yes. Avoid doing so by hand.
Can you mix and match approach? For example, one batch at 6 months and two at three months?No.
What if a drug uses multiple APIs? Do tests need to be conducted on each API, or only in combination?It depends. Several approaches are available. See guidance.
What does FDA mean by "small" scale?It depends on the type of drug substance. See guidance.
Should batches be produced at the proposed commercial site?Yes.

ANDAs: Stability Testing of Drug Substances and Products: Questions and Answers (FR)


© 2023 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy