New Requirements of the FDA on Stability Testing of Generic Drugs

So far, those who have been applying by the FDA for the authorisation of a generic medicinal product for the American market could (with regard to the data for stability testing) refer to a communication from the FDA to the pharmaceutical industry from 1995. In this "Letter to Industry", the "Office of Generic Drugs (OGD)" explained that stability data from studies under long-term conditions (e.g. 25°C +/-2°C; 60% +/- 5% rel. humidity) are accepted as described in the guideline ICH Q1A(R2).

As a result of numerous requests from the industry on this issue, the FDA has now extended and clarified its requirements. In June of this year, a "Guidance for Industry" entitled "ANDAs: Stability Testing of Drug Substances and Products" was released. The guideline lists in 7 points the expectations of the FDA regarding the data and information required about the stability of the medicinal product in an application for generic medicinal products (Abbreviated New Drug Application; ANDA):

1. Stability data from 3 pilot scale batches or 2 pilot scale batches and 1 small-scale batch if the size of the pilot does not follow ICH recommendations. The applicant should provide a justification.

2. 6 months of data that include accelerated and long-term conditions at the time of submission. For intermediate conditions, the requirements laid down in the ICH Guideline have to be complied with.

3. Use of multiple batches as appropriate.

4. Manufacturing and packaging of the drug product have to use 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, Appendix A.

As in other FDA Guidelines, a deviating procedure is also accepted. However, a justification has to be given that there is no doubt about the stability of the generic medicinal product with the alternative procedure.