FDA Goes into Detail About Generic Drug Stability Testing
Posted 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The guidance, ANDAs: Stability Testing of Drug Substances and Products: Questions and Answers, is a follow-up to a draft guidance released in September 2012, and then finalized in June 2013.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.
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FDA's latest Q&A guidance finalizes an earlier draft guidance by the same title released in August 2013 which clarified a bunch of specific-but nevertheless important-issues.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)