Quality Management System for Active pharmaceutical

Quality Management System - integrating GMP into ISO4.6.2 Validation of an API manufacturing process generally starts during the developmentphase when the quality critical issues are identified and suitable process parameterranges initially evaluated. Information obtained during scale-up activities should beused to confirm and refine this evaluation. Manufacture of production scale batchesusually provides evidence that the process is reproducible (see Annex C).4.7 ChangesDesign changes (including minor modifications) should be identified to all relevantfunctions, documented, reviewed, and approved by a suitable level of authority priorto implementation (see Annex D).4.8 Stability testing, retest and expiry dateThe date after which an API should be retested should be based on the findings ofwell designed stability studies. The continuing validity of retest and expiry datesshould be verified by monitoring current production. A company policy regardingthe relationship between retest and expiry date should be established. The protocolfor conducting stability studies should be based on internationally accepted conceptssuch as the ICH (International Conference on Harmonisation) Harmonised TripartiteGuideline "Stability Testing of New Drug Substances and Products".With regard to existing products described in the pharmacopoeia (includingdegradation products) produced according to well established processes, an expiryand/or retest date could be determined on the basis of historical data and/orpublished literature.4.8.1 Storage Conditions, retest and expiry date4.8.1.1 The conditions under which API are stored should be based on results of stabilitystudies, which take into account the potential effects of storage time, temperatureand relative humidity.4.8.1.2 Based on the results of stability studies, a date should be established after which ananalytical retest of the API should be carried out before further use.4.8.1.3 The assigned retest and expiry dates may differ for different climatic zones. This willdepend on the differences observed or measured in the models used in the stabilitystudies to reflect the potential climatic conditions under which the product may bestored.4.8.1.4 The written specification which should be met at the retest and expiry date may bedifferent from the (more stringent) specification applicable at the time of release.20