Initial assay of a product found as 102% and after 6months accelerated condition the assay found as 93% which is within spec but significant change occurred. In such case can the shelf life be declared as 02 years ?
According to ICH Q1 A (R2) Guideline - STABILITY TESTING OF
NEW DRUG SUBSTANCES AND PRODUCTS and ICH QE - EVALUATION FOR STABILITY DATA, the following criteria should be considered for assigning the shelf life of a drug product.
If long-term studies are conducted at 25°C ± 2°C/60% RH ± 5% RH and “significant change” occurs at any time during 6 months’ testing at the accelerated storage condition, additional testing at the intermediate storage condition at 30°C ± 2°C/65% RH ± 5% RH should be conducted for 6 months and evaluated against significant change criteria.
Where “significant change” occurs at the accelerated condition, the retest period or shelf life would depend on the outcome of stability testing at the intermediate and long-term conditions (25°C ± 2°C/60% RH ± 5% RH
or 30°C ± 2°C/65% RH ± 5% RH)
In general, “significant change” for a drug product is defined as:
- A 5% change in assay from its initial value; or failure to meet the acceptance criteria for potency when using biological or immunological procedures;
- 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, resuspendibility, caking,
hardness, dose delivery per actuation); however, some changes in physical
attributes (e.g., softening of suppositories, melting of creams) may be expected under accelerated conditions; and, as appropriate for the dosage form: - Failure to meet the acceptance criterion for pH; or
- Failure to meet the acceptance criteria for dissolution for 12 dosage units.
If significant change occurs between 3 and 6 months’ testing at the accelerated storage condition, the proposed retest period or shelf life should be based on the long-term data. Extrapolation is not considered appropriate. In addition, a retest period or shelf life shorter than the period covered by long-term data could be called for. If the long-term data show variability, then verification of the proposed retest period or shelf life by statistical analysis can be appropriate.
As in your case, the assay value has fallen more than 5%, this will be a significant change and would require additional testing as stated above. Based on this outcome the shelf life can be decided.
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