Stability Testing of New Drug Substances and Products
7
Stability studies should be performed on each individual strength and container size
of the drug product unless bracketing or matrixing is applied.
Other supporting data can be provided.
2.2.4. Container Closure System
Stability testing should be conducted on the dosage form packaged in the container
closure system proposed for marketing (including, as appropriate, any secondary
packaging and container label). Any available studies carried out on the drug product
outside its immediate container or in other packaging materials can form a useful
part of the stress testing of the dosage form or can be considered as supporting
information, respectively.
2.2.5. Specification
Specification, which is a list of tests, reference to analytical procedures, and proposed
acceptance criteria, including the concept of different acceptance criteria for release
and shelf life specifications, is addressed in ICH Q6A and Q6B. In addition,
specification for degradation products in a drug product is addressed in Q3B.
Stability studies should include testing of those attributes of the drug product that
are susceptible to change during storage and are likely to influence quality, safety,
and/or efficacy. The testing should cover, as appropriate, the physical, chemical,
biological, and microbiological attributes, preservative content (e.g., antioxidant,
antimicrobial preservative), and functionality tests (e.g., for a dose delivery system).
Analytical procedures should be fully validated and stability indicating. Whether and
to what extent replication should be performed will depend on the results of
validation studies.
Shelf life acceptance criteria should be derived from consideration of all available
stability information. It may be appropriate to have justifiable differences between
the shelf life and release acceptance criteria based on the stability evaluation and the
changes observed on storage. Any differences between the release and shelf life
acceptance criteria for antimicrobial preservative content should be supported by a
validated correlation of chemical content and preservative effectiveness demonstrated
during drug development on the product in its final formulation (except for
preservative concentration) intended for marketing. A single primary stability batch
of the drug product should be tested for antimicrobial preservative effectiveness (in
addition to preservative content) at the proposed shelf life for verification purposes,
regardless of whether there is a difference between the release and shelf life
acceptance criteria for preservative content.
2.2.6. Testing Frequency
For long term studies, frequency of testing should be sufficient to establish the
stability profile of the drug product. For products with a proposed shelf life of at least
12 months, the frequency of testing at the long term storage condition should
normally be every 3 months over the first year, every 6 months over the second year,
and annually thereafter through the proposed shelf life.
At the accelerated storage condition, a minimum of three time points, including the
initial and final time points (e.g., 0, 3, and 6 months), from a 6-month study is
recommended. Where an expectation (based on development experience) exists that
results from accelerated testing are likely to approach significant change criteria,