The US Food and Drug Administration (FDA) has released a new 2 page guidance for industry that pertains to stability testing recommendations for generic drug products submitted under 505(j) of the Federal Food, Drug and Cosmetic Act (FD&C Act) as an abbreviated new drug application (ANDA) or a drug master file (DMF).
The June 2013 guidance document issued by CDER, ANDAs: Stability Testing of Drug Substances and Products, which replaces the 1995 letter from OGD , explains that, "Over the past few years, the Office of Generic Drugs (OGD) has received numerous inquiries about what stability data FDA expects in ANDA submissions."
In the document, the FDA goes on to say "Currently, the only published direction from OGD is contained in a1995 letter to industry which states that OGD will accept ICH recommended long-term room temperature conditions for stability studies (i.e., 25±2°C, 60±5% RH),"
And, the FDA continues, "Although adequate in the context of other guidance existing at that time, this recommendation is no longer sufficient to serve as a basis for stability testing for ANDAs."
This new FDA guidance document explicitly points to several guidelines put forth by the International Conference on Harmonization (ICH), a regulatory harmonization group made up of the US, EU and Japan and focused on pharmaceutical products. 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
■ Q1E Evaluation of Stability Data.
The selection of these ICH guidelines may seem somewhat out of place, given the 1995 letter from OGD. But, the FDA explains that these ICH documents were developed for the purposes of innovative pharmaceuticals submitted under a new drug application (NDA) – not generic ones submitted under an ANDA. Their purposes notwithstanding, FDA said it believes “the recommendations also should be applied to ANDAs" as well.
FDA goes on to list seven recommendations for generic drug sponsors following ICH's stability recommendations:
1. Submit data from three pilot scale batches or two pilot scale batches and one small
scale batch. If the size of the pilot scale batch does not follow ICH recommendations,
the applicant should provide a justification.
2. 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.
3. Use multiple lots of drug substance as appropriate.
4. Manufacture and package the drug product using principles that are representative
of the commercial process.
5. Provide a fully packaged primary batch.
6. Use drug product from all three primary batches when using bracketing and matrixing
designs under ICH Q1D.
7. Provide statistical analysis of the data as appropriate, in accordance with ICH Q1E,
The new guidance document goes on to state that any deviations from its recommendations should be justified in the ANDA application.