Out of Specification Department of Chemistry出规格化学系.pptVIP

M.KOUPPARIS Out of Specification MHRA MEDICINE AND HEALTHCARE PRODUCTS REGULATORY AGENCY Laboratory Analysis (1) Investigations of Out of Specification (OOS) / Out of Trend (OOT)/ Atypical -results have to be done in cases of: – Batch release testing and testing of starting materials. – In-Process Control testing: if data is used for batch calculations/decisions and if in a dossier and on Certificates of Analysis. – Stability studies on marketed batches of finished products and or active pharmaceutical ingredients, on-going / follow up stability (no stress tests) Laboratory Analysis (2) – Previous released batch used as reference sample in an OOS investigation showing OOS or suspect results. – Batches for clinical trials. Laboratory Analysis (3) All solutions and reagents must be retained until all data has been second person verified as being within the defined acceptance criteria. Pharmacopoeia have specific criteria for additional analyses of specific tests (i.e. dissolution level specification for S1, S2 S3 testing; Uniformity of dosage units specification for testing of 20 additional units; Sterility Testing). Laboratory Analysis (4) However if the sample test criteria is usually the first level of testing and a sample has to be tested to the next level this should be investigated as it is not following the normal trend. Laboratory Analysis (5) The OOS process is not applicable for In-process testing while trying to achieve a manufacturing process end-point, i.e.: - adjustment of the manufacturing process. (e.g. pH, viscosity), - for studies conducted at variable parameters to check the impact of drift (e.g.process validation at variable parameters). OOS / OOT Result (1) Out-of-Specification (OOS) Result – Test result that does not comply with the predetermined acceptance criteria, for example: - filed applications, drug master files, approved marketing submissions, - official compendia - internal acceptance criteria OOS / OOT Result