01-12-2012, 05:37 PM
STABILITY STUDIES
1STABILITY STUDIES.ppt (Size: 172.5 KB / Downloads: 330)
Applicable guidelines
WHO Guidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms.
WHO working document QAS/05.146 - Stability Studies in a Global Environment.
ICH guidelines Q1A-Q1F. Stability testing of new APIs and FPPs has been harmonized at global level.
WHO Guideline on Submission of Documentation for Prequalification of Multi-source (Generic) Finished Pharmaceutical Products (FPPs) Used in the Treatment of HIV/AIDS, Malaria and Tuberculosis. Annex 4. Stability requirements for variations and changes to prequalified FPPs
Supplement 2 Extension of the WHO List of Stable (not easily degradable ) APIs.
Selected definitions
Re-test date
The date after which samples of an API should be examined to ensure that the material is still in compliance with the specification and thus suitable for use in the manufacture of a given FPP.
Shelf life (expiration dating period, conformance period)
The time period during which an API or a FPP is expected to remain within the approved shelf-life specification, provided that it is stored under the conditions defined on the container label.
Supporting data
Data, other than those from formal stability studies, that support the analytical procedures, the proposed re-test period or shelf life, and the label storage statements. Such data include
stability data on early synthetic route batches of API, small-scale batches of materials, investigational formulations not proposed for marketing, related formulations, and product presented in containers and closures other than those proposed for marketing;
information regarding test results on containers; and
other scientific rationales.
Forced degradation tests
To identify potential degradants (degradation pathways) of the API and assess if they can be formed during manufacture or storage of the FPP (intrinsic stability of the API).
To validate the stability indicating power of the analytical procedures.
To identify stability-affecting factors such as ambient temperature, humidity and light and to select packing materials, which protect the FPP against such effects.
Stability results
A storage statement should be proposed for the labeling (if applicable), which should be based on the stability evaluation of the API.
A re-test period should be derived from the stability information, and the approved retest date should be displayed on the container label.
An API is considered as stable if it is within the defined/regulatory specifications when stored at 30±2oC and 65±5% RH for 2 years and at 40±2oC and 75±5%RH for 6 months.
Selection of Batches
At the time of submission data from stability studies should be provided for batches of the same formulation and dosage form in the container closure system proposed for marketing.
Stability data on three primary batches are to be provided. The composition, batch size, batch number and manufacturing date of each of the stability batches should be documented and the certificate of analysis at batch release should be attached.
Where possible, batches of the FPP should be manufactured by using different batches of the API.
Significant Change of FPPs
A 5% change in assay from its initial value.
Any degradation product exceeding its acceptance criterion.
Failure to meet the acceptance criteria for appearance, physical attributes, and functionality test (e.g., color, phase separation, hardness).
As appropriate for the dosage form, e.g., failure to meet the acceptance criteria for dissolution for 12 dosage units.