General requirements for change control
Article 59
1. A formal change control system shall be established to evaluate all changes that may affect the production and control of the intermediate or active substance. 2. Written procedures shall describe the identification, documentation, appropriate review and approval of changes in raw materials, specifications, analytical methods, premises, support systems, equipment (including computer hard- and software), processing steps, labelling and packaging materials. 3. Any proposals for changes relevant to the good manufacturing practices shall be drafted, reviewed and approved by the appropriate organisational unit, and reviewed and approved by the quality unit. 4. The potential impact of proposed changes on the quality of the active substances or intermediates thereof shall be evaluated. A classification procedure may contribute to determine the level of testing, validation and documentation needed to justify changes to a validated process. Changes shall be classified (e.g. as minor or major) depending on the nature and extent of the changes and the effects those changes may have on the process. 5. A scientific assessment shall be carried out to determine which additional testing and validation studies are appropriate to justify a change in a validated process. 6. All documents affected by the changes shall be revised and updated where approved changes are implemented. 7. After implementation of the change, an evaluation of the first batches produced or tested under the change shall be performed. 8. The potential for critical changes to affect established retest or expiry dates shall be evaluated. Where necessary, samples of the active substances or intermediates thereof produced by the modified process shall be placed on an accelerated stability programme and added to the on-going stability programme. 9. Manufacturers of the veterinary medicinal product shall be notified of changes from established production and process control procedures that may impact the quality of the active substance used in the veterinary medicinal product.