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Shelf-life and its estimation in drug stability studies |
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| Authors: | W Liu JC Hsu F Bretz AJ Hayter Y Han |
| Institution: | 1. S3RI, University of Southampton, Southampton, UK;2. School of Maths, University of Southampton, Southampton, UK;3. Department of Statistics, Ohio State University, Columbus, OH, USA;4. Novartis Pharma AG, Basel, Switzerland;5. Shanghai University of Finance and Economics, People's Republic of China;6. Department of Statistics and Operations Technology, University of Denver, Denver, CO, USA |
| Abstract: | One important property of any drug product is its stability over time. Drug stability studies are routinely carried out in the pharmaceutical industry in order to measure the degradation of an active pharmaceutical ingredient of a drug product. One important study objective is to estimate the shelf-life of the drug; the estimated shelf-life is required by the US Food and Drug Administration to be printed on the package label of the drug. This involves a suitable definition of the true shelf-life and the construction of an appropriate estimate of the true shelf-life. In this paper, the true shelf-life Tβ is defined as the time point at which 100β% of all the individual dosage units (e.g. tablets) of the drug have the active ingredient content no less than the lowest acceptable limit L, where β and L are prespecified constants. The value of Tβ depends on the parameters of the assumed degradation model of the active ingredient content and so is unknown. A lower confidence bound T?β for Tβ is then provided and used as the estimated shelf-life of the drug. |
| Keywords: | acceptance set confidence set lower confidence bound confidence level drug stability study shelf-life linear regression mixed-effects linear regression |