Drug stability expiration dating
Some firms have chosen, for economical purposes, random dates to test all stability samples of a given product.
As long as there is at least one test performed annually, this approach can be quite satisfactory.
This can be done, as an example, by taking a sample product that has been at room temperature for one year and subjecting that sample to accelerated temperature conditions.
The expiration dating period used would then be the sum of that justified individually at each storage condition.
While many USP tests are specific for the drug or its degradates and may be used for stability testing, some USP monographs do not incorporate stability indicating tests. Kaybel that when a “new drug” was repackaged, the repacker did not have to obtain pre-market approval of the repackaged product or the firm’s repacking procedures.
Additionally, it may be unreasonable to expect a manufacturer to develop specific methodology for each component of some multi-component drugs containing ingredients of botanical origin such as benzoin, Peruvian balsam or tolu balsam. However, the repacker is subject to applicable current good manufacturing practices.
While 211.166 (a) (3) merely requires that test methods be reliable, meaningful, and specific, section 211.165 (e) gives more guidance by stating that the accuracy, sensitivity, specificity, and reproducibility of test methods employed by the firm shall be established and documented.
It is the policy of the Center for Drugs and Biologics to allow repacking into container-closure systems that can be demonstrated to be at least as protective or more protective than the original system without performing new stability studies prior to marketing.
Manufacturers, who contract with analytical laboratories to perform either end product testing or stability studies, or who produce product under contract for other firms are ultimately responsible for the quality of the product and must have copies of all analytical procedures employed and the appropriate documentation to assure their validity on file.
Likewise, repackers who rely on stability studies performed by the manufacturer must have copies of all analytical data necessary to support the expiration dating period.
If a product was stored under controlled conditions, those actual conditions (temperature and humidity) should be recorded.
Merely stating that a product was stored at room temperature is not sufficient for purposes of determining stability.
Written Stability Testing Program The absence of a written protocol for stability testing is cause to initiate regulatory action against the product and/or the responsible firm. Supportive Stability Data Initial stability testing by accelerated testing may be performed on a batch smaller than the normal production size as long as the batch is produced by similar equipment as would be used for regular production.