General requirements for premises
1. Premises used for the manufacture or import of veterinary medicinal products 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 products.
2. Premises shall be designed and equipped so as to afford maximum protection against the entry of insects or other animals. Measures to prevent the entry of unauthorised people shall be implemented.
3. Production, storage and quality control areas shall not be used as a right of way by personnel not working in those areas.
Production areas
1. Cross-contamination shall be prevented by the appropriate design and operation of the premises. The measures to prevent cross-contamination shall be commensurate with the risks. Quality risk management principles shall be used to assess and control the risks.
2. Depending on the level of risk and based on the outcome of a quality risk management assessment, it may be necessary to dedicate premises and equipment for manufacturing or packaging operations to a particular product or product class. Dedicated premises shall be required when a risk cannot be adequately controlled by operational or technical measures.
3. The layout of the premises shall permit the production to take place in areas connected in a logical order corresponding to the sequence of the operations and the required level of cleanliness.
4. The arrangement of the working and in-process storage space shall be adequate to minimise the risk of confusion between different products or their components, to avoid cross-contamination, and to minimise the risk of omission or the wrong application of any of the manufacturing or control steps.
5. Where the materials used in the production of a veterinary medicinal product, an intermediate product or bulk product are exposed to the environment, the interior surfaces of the area (walls, floors and ceilings) shall be smooth, free from cracks and open joints, shall not shed particulate matter, and shall permit easy and effective cleaning and, if necessary, disinfection.
6. Pipework, light fittings, ventilation points and other services shall be designed and sited so as to avoid the creation of recesses that are difficult to clean. As far as possible, for maintenance purposes, they shall be accessible from outside the manufacturing areas.
7. Drains shall be of adequate size and have trapped gullies. Open channels shall be avoided where possible but, where they are necessary, they shall be shallow to facilitate cleaning and disinfection.
8. Production areas shall be effectively ventilated, with air control facilities (including temperature and, where necessary, humidity and filtration) appropriate to the products handled, to the operations undertaken within them, and to the external environment.
9. In cases where dust is generated, such as during sampling, weighing, mixing and processing operations, or packaging of dry products, specific measures shall be implemented to avoid cross-contamination and to facilitate cleaning.
Quality control areas
1. Quality control areas shall generally be separated from production areas. Laboratories for the control of biologicals, microbiologicals and radioisotopes shall also be separated from each other. However, in-process controls may be carried out within the production area provided that they do not carry any risk for the products.
2. Quality control areas shall be designed to suit the operations to be carried out in those areas. Sufficient space shall be given to avoid mix-ups and cross-contamination during testing. Adequate storage space for samples and records shall be available. Separate rooms may also be required to protect sensitive instruments from vibration, electrical interference, humidity, or any other condition that may have a negative impact on their performance.
3. Special precautions shall be taken in quality control areas handling hazardous substances, such as biological samples.
Storage areas
1. Storage areas shall be of sufficient capacity to allow the orderly storage of the various categories of materials and products, including products in quarantine, and products released, rejected, returned or recalled.
2. Receiving and dispatch bays shall protect materials and products from the weather. Reception areas shall be designed and equipped to allow containers of incoming materials to be cleaned where necessary before storage.
3. Materials or products that present a specific risk shall be stored in safe and secure areas.
4. Where quarantine status is ensured by storage in separate areas, those areas shall be clearly marked and their access restricted to authorised personnel. Any system replacing a physical quarantine shall provide equivalent security.
5. Separate areas shall be provided for the storage of rejected, recalled or returned materials or products. Where sampling is conducted in the storage area, it shall be conducted in such a way as to prevent contamination or cross-contamination.
Ancillary areas
1. Rest and refreshment rooms shall be separate from production, storage and quality control areas. Toilets shall not directly communicate with production, storage or quality control areas.
2. Maintenance workshops shall -as far as possible- be separated from production areas. Whenever parts and tools are stored in the production area, they shall be kept in rooms or lockers reserved for that use.
3. Animals shall be kept in separated areas, with a separate entrance and air handling facilities.
Temperature and environmental controls
1. Lighting, temperature, humidity and ventilation conditions shall be appropriate and such that they do not adversely affect, directly or indirectly, the veterinary medicinal products during their manufacture and storage, or the accurate functioning of equipment. Where special conditions are required (e.g. temperature, humidity), these shall be specified and monitored.
2. Appropriate measures to monitor key environmental parameters shall be applied at the manufacturing site.
Equipment
1. Equipment used in production or control operations shall be suitable for its intended purpose and shall not present any hazard to the product. The parts of production equipment that come into contact with the product shall not have any unwanted reactive, additive, adsorptive or absorptive properties that may affect the quality of the product.
2. Equipment that is critical to the quality of the products shall be subject to appropriate qualification.
3. Balances and measuring equipment shall be of an appropriate range and precision to ensure the accuracy of weighing operations.
4. Equipment shall be operated and maintained in such a way as to minimise the risk of error and to avoid contamination, cross-contamination and, in general, any adverse effect on the quality of the product.
5. Equipment shall be calibrated, inspected or checked, as appropriate, at defined intervals to ensure an adequate performance. In the case of computerised systems, the checks shall include an evaluation of the ability of the system to ensure data integrity. Appropriate records of those checks shall be maintained. Additional requirements relevant to the use of computerised systems are laid down in Annex IV.
6. Equipment shall be adequately cleaned to avoid the risk of contamination for the products. The cleaning or decontamination procedures shall be detailed in writing, ensuring that the cleaning equipment does not become a source of contamination. Equipment shall only be stored in a clean and dry condition.
7. The location and installation of the equipment shall be adequate to minimise risks of errors or contamination. In general, equipment, including laboratory equipment, shall not be moved between high-risk areas. If equipment is moved between high-risk areas, appropriate measures shall be applied to avoid the risk of cross-contamination. Where appropriate, the qualification status of the equipment moved shall also be reconsidered.
8. Fixed pipework shall be clearly labelled to indicate the content and, where applicable, the direction of flow.
9. Water for pharmaceutical use and, where appropriate, other water pipes shall be sanitised according to written procedures that detail the action limits for microbiological contamination and the measures to be taken.
10. Defective equipment shall be removed from production and quality control areas or, if the removal thereof is not possible, it shall be clearly labelled as defective.
Qualification of premises and equipment
1. Premises and equipment used in the manufacture of veterinary medicinal products, including utilities and systems, shall be qualified as appropriate to ensure that they are adequate for the intended operations. The qualification shall be performed in accordance with the requirements laid down in Annex V.
2. Decisions on the scope and extent of the qualification shall be based on a risk-assessment, which shall be documented.
3. Before starting the manufacture of a new type of veterinary medicinal product in premises that have already been qualified, the manufacturer shall assess if there is a need for re-qualification having regard to the specific risks and characteristics of the new manufacturing process or new product.
4. Premises and equipment shall be re-evaluated at appropriate intervals to confirm that they remain suitable for the intended operations.
Source: EUR-Lex (Publications Office of the EU), © European Union, reuse permitted under Commission Decision 2011/833/EU.
