lower confidence bound lower specification limit Storage time
However, the most important issue for determination of shelf lives for frozen drug products is that the same acceptable lower specification limit cannot be used for both frozen and thawed studies. The strength of a frozen drug product at the time it is to be administered at room temperature (25°C) is very likely to be below the acceptable lower specification limit if it is used to establish the shelf life for the frozen product. Second, determination of the shelf life for refrigerated and ambient conditions should be analyzed separately from that for frozen conditions. The shelf life for frozen conditions, measured in months, is usually much longer than those under refrigerated or ambient conditions, measured in either weeks or days. Therefore, the design for the thawed study should have different measures for time points than the frozen study. Note that if one uses only one regression model to fit the data from both states, the resulting estimated shelf lives under refrigerated and ambient conditions may not be reliable, due to rapid degradation and a much shorter time interval for the thawed study.