General requirements for premises
Article 13
1. Premises used for manufacture of active substances shall be suitable for the intended operations. In particular, the premises shall be designed or adapted, equipped, operated, cleaned and maintained to minimise the opportunity for extraneous contamination, cross-contamination, the risk of errors and any adverse effect on the quality of the active substances. 2. The flow of materials and personnel throughout the premises shall be designed to avoid mix-ups or contamination. 3. Defined areas or control systems shall be in place for the following actions: (a) receipt, identification, sampling, and quarantine of incoming materials, pending their release or rejection; (b) production operations; (c) laboratory operations; (d) packaging and labelling operations; (e) quarantine before release or rejection of active substances and intermediates thereof; (f) sampling of active substances and intermediates thereof; (g) storage of released materials; (h) holding rejected materials before further disposition (e.g. return, reprocessing or destruction). 4. Adequate washing and toilet facilities for personnel shall be provided. Washing facilities shall be maintained in clean state and equipped with hot and cold water as appropriate, soap or detergent, and air dryers or single service towels. The washing and toilet facilities shall be separate from manufacturing areas. 5. Adequate facilities for showering or changing clothes shall be provided, where appropriate. 6. Laboratory areas and operations shall generally be separated from production areas. 7. By way of derogation from paragraph 6, laboratory areas, may be located in production areas, provided the following conditions are met: (a) operations of the production process do not adversely affect the accuracy of the laboratory measurements; (b) the laboratory and its operations do not adversely affect the production process, or the active substances or intermediates thereof. 8. All utilities affecting product quality shall be qualified and monitored (e.g. steam, gases, compressed air, heating, ventilation and air conditioning). Action shall be taken when limits for those utilities are exceeded. Drawings for those utility systems shall be available. 9. Adequate ventilation, air filtration and exhaust systems shall be provided, where appropriate. Those systems shall be designed and constructed to minimise risks of contamination and cross-contamination and shall include equipment for control of air pressure, microorganisms, if appropriate, dust, humidity, and temperature, as appropriate to the stage of manufacture. Particular attention to minimise the risks of contamination and cross-contamination shall be given to areas where active substances are exposed to the environment. 10. If air is recirculated to production areas, appropriate measures shall be taken to control risks of contamination and cross-contamination. 11. Fixed pipework shall be appropriately identified by identifying individual lines, documentation, computer control systems, or by alternative means. 12. Drains shall be of adequate size and shall be provided with an air break or a suitable device to prevent back-flow, where appropriate. 13. Adequate lighting shall be provided in all areas to facilitate cleaning, maintenance, and proper operations. 14. Sewage, refuse, and other waste in and from buildings and the immediate surrounding area shall be disposed of in a safe, timely, and sanitary manner. Containers and pipes for waste material shall be clearly labelled. 15. A site master file shall be prepared for every manufacturing site, which shall provide a high-level description of the premises, of the activities conducted at the manufacturing site and the quality system implemented. The site master file shall follow the template provided for in Annex VI to Implementing Regulation (EU) 2025/2091 on good manufacturing practice for veterinary medicinal products.