Process validation
Article 54
1. Prospective validation shall be used for all active substance processes. 2. Prospective validation performed on an active substance process shall be completed before the commercial distribution of the veterinary medicinal product manufactured from that active substance. 3. By way of derogation from paragraph 1, concurrent validation may be conducted in the following cases: (a) data from replicate production runs are unavailable because only a limited number of active substance batches have been produced; (b) active substance batches are produced infrequently; or (c) active substance batches are produced by means of a validated process that has been modified. 4. Prior to the completion of concurrent validation, batches may be released and used in the manufacturing of a veterinary medicinal product based on thorough monitoring and testing of the active substance batches. 5. By further way of derogation from paragraph 1, retrospective validation may be performed for well-established processes that have been used without significant changes to active substance quality due to changes in raw materials, equipment, systems, premises or the production process. That validation approach may be used if all the following conditions are met: (a) critical quality attributes and critical process parameters have been identified; (b) appropriate in-process acceptance criteria and controls have been established; (c) there have not been significant process or product failures attributable to cause other than operator error or equipment failures unrelated to equipment suitability; (d) impurity profiles have been established for the existing active substance. 6. Batches selected for retrospective validation shall be: (a) representative of all batches made during the review period, including any batches that failed to meet specifications; (b) sufficient in number to demonstrate process consistency. 7. Retained samples may be used for retrospective validation testing.