guidelines on variations to a registered pharmaceutical product

Guidelines on Variations to a Registered Pharmaceutical Product8 Submission of a new or updated confirmation of active pharmaceutical ingredient-prequalification document..........................................................................................................169 Submission of a new or updated transmissible spongiform encephalopathy EuropeanPharmacopoeia Certificate of Suitability for an excipient or active pharmaceutical ingredient(addition or replacement)............................................................................................................175.3 Quality changes........................................................................................................................ 185.3.1 Drug substance (or active pharmaceutical ingredient)................................................................185.3.1.1 Manufacture...................................................................................................................1810 Replacement or addition of a new manufacturing site or manufacturer of an activepharmaceutical ingredient involving:................................................................................... 1811a change or addition of a manufacturing block/unit at a currently accepted site of activepharmaceutical ingredient manufacture.............................................................................. 2012a change in the manufacturing process of the active pharmaceutical ingredient................... 2113 Change in the in-process tests or limits applied during the manufacture of the activepharmaceutical ingredient:.................................................................................................. 2314 Change in batch size of the active pharmaceutical ingredient involving:............................ 2415 Change to the specifications or analytical procedures applied to materials used in themanufacture of the active pharmaceutical ingredient (e.g. raw materials, startingmaterials, reaction intermediates, solvents, reagents, catalysts) involving:........................ 255.3.1.2 Control of the active pharmaceutical ingredient by the active pharmaceuticalingredient manufacturer ................................................................................................2616 Changes to the test parameters, acceptance criteria, or analytical procedures of theactive pharmaceutical ingredient manufacturer that do not require a change to thefinished pharmaceutical product manufacturer’s active pharmaceutical ingredientspecifications involving:....................................................................................................... 265.3.1.3 Control of the active pharmaceutical ingredient by the finished pharmaceuticalproduct manufacturer.....................................................................................................2717 Change to the test parameters or acceptance criteria of the active pharmaceuticalingredient specifications of the finished pharmaceutical product manufacturerinvolving:............................................................................................................................. 2718 Change to the analytical procedures used to control the active pharmaceutical ingredientby the finished pharmaceutical product manufacturer involving:........................................ 295.3.1.4 Container-closure system..............................................................................................3119a Change in the immediate packaging (primary and functional secondary components)for the storage and shipment of the active pharmaceutical ingredient................................ 3120 Change in the specifications of the immediate packaging for the storage and shipmentof the active pharmaceutical ingredient involving:............................................................... 3121 Change to an analytical procedure on the immediate packaging of the activepharmaceutical ingredient involving:................................................................................... 325.3.1.5 Stability...........................................................................................................................3322 Change in the retest period/shelf-life of the active pharmaceutical ingredient involving:.... 3323 Change in the labelled storage conditions of the active pharmaceutical ingredientinvolving:............................................................................................................................. 345.3.2 Drug product (or finished pharmaceutical product).....................................................................34Doc. No.: DAR/GDL/005 Revision Date: 8 th July 2013 Review Due Date: 16 th July 2016Revision No.: 1 Effective Date : 16 th July 2013 Page iv of 70