STABILITY STUDIES OF PHARMACEUTICAL PRODUCTS IN INDUSTRY
EXPIRATION DATE/SHELF LIFE
An expiration date is defined as the time upto which the product will remain stable when stored under recommended storage conditions. Thus, an expiration date is the date beyond which it is predicted that the product may no longer retain fitness for use. If the product is not stored in accordance with the manufacturer’s instructions, then the product may be expected to degrade more rapidly.
Shelf life is the time during which the product, if stored appropriately as per the manufacturer’s instructions, will retain fitness for use (>90% of label claim of potency).
The expiration date is also defined as the date placed on the container/labels of a drug product designating the time during which a batch of the product is expected to remain within the approved shelf life specifications, if stored under defined conditions and after which it should not be used.
ESTIMATION OF SHELF LIFE
The shelf life is determined from the data obtained from the long term storage studies. The data is first linearized and test for goodness of fit is applied.
For determination of significance of difference in case of slope or intercept, statistical tests like t-test should be applied. The data is available in the form of only five data points i.e. 0, 3, 6, 9 and 12 months, either pooled from the three batches or from the three individual batches if they are not fit for pooling. In case data is not fit for pooling, stability estimates are to be made on the worst batch.
The shelf life/expiry date is determined from the regression line of this five point data based on calculation of 95% one-sided confidence limit. For reading the expiry date, 90% drug concentration is considered as the lowest specification limit and the point where the extension line cuts the 95% confidence limit line is taken as an expiry date.
Because shelf life derived from the intersection of the lower 90% confidence bound and 90% potency value has a 95% confidence level, therefore there is only a 5% chance that our estimate of the shelf life will be too high..
For new drugs, it is a general practice to grant only two year expiry initially, which is based on satisfactory one year long-term and 6 months accelerated stability data. The expiry date for third and later years is allowed only on production of real-time data for the subsequent years.
Most pharmaceutical products are characterized by only one shelf life. However, in some cases a product may have two e.g. a freeze-dried (lyophilized) protein product may have only 1 shelf life, say 2 years, for the product stored in the dry condition and a 2nd shelf life, say 2 days, for the product when it has been reconstituted with the appropriate vehicle and is ready for injection.
CONFORMANCE PERIOD
The conformance period is determined from the intersection of the lowest (or highest) acceptable value of the stability parameter and the 95% confidence bound of the regression line. Shelf life assigned to a product is equal to, or less than, the, conformance period and is usually a convenient rounded off number (e.g. 7 days, 1 month, 1 year, 18 months, or 2, 3, or 5 years). e.g. if for 3 separate pharmaceutical products we obtained conformance periods of 13.2, 26.1 and 39.4 months, we would probably assign shelf lives of 12, 24 and 36 months to the 3 products. The difference between conformance period and the assigned shelf life is that conformance period provides an extra stability reserve.
