Premises and equipment

Principle

300. Premises, facilities and equipment should be located, designed, constructed, adapted, maintained, and suitable for its intended purpose. Their layout and design should aim to minimise the risk of errors and permit effective cleaning and maintenance in order to avoid contamination, build up of dirt and, in general, any adverse effect on the quality of products.
     • In order to minimise the risk of microbiological and particulate contamination, the manufacture of sterile products, or products required to have a low bioburden, should be subject to special environmental controls (e.g. Clean rooms, biological safety cabinets). Where required, applicable code clauses in Annex 1 of the mandated Code of GMP for Medicinal Products should apply.
     • Premises, facilities and equipment which, is critical to the control of processing should be formally qualified.

Premises

General

301. The manufacture of products should be carried out under appropriate and specified conditions, and each area, including mobile sites, should be designed and maintained to suit the operation(s) to be performed.
302. Premises should be designed and equipped so as to afford maximum protection against the entry of insects or other animals.
303. Steps should be taken in order to prevent the entry of unauthorised personnel to premises and restricted access areas. Precautions should be taken to check visitors to the premises, including external maintenance people and contractors, and to provide an appropriate level of access and supervision for their activities.
304. Where appropriate, contingency plans for breakdowns in critical services or equipment should be developed and regularly reviewed. For example, in the event of power failure, where necessary there should be access to a power source to allow the maintenance of critical services and equipment to permit the safe conclusion of activities in progress.
305. Lighting, temperature, humidity, air quality and ventilation should be appropriate and such that they do not adversely affect either the products during their manufacture and storage, or the correct functioning of equipment.
306. Premises for the manufacture of products should be specifically designed and used so as to avoid mix-ups or contamination.
307. Donor interview facilities should enable interviews to be conducted in private.

Processing areas

308. Materials of construction should not pose a source of contamination to the product. Critical surfaces in processing areas should be non-porous, smooth, and easily cleanable.
309. Where environmental conditions (e.g. temperature, humidity, air quality) could have an adverse effect on product quality, appropriate conditions should be defined, implemented and monitored.
310. For products requiring control of microbiological bioburden, the manufacturer should establish and document the environmental requirements to which product is exposed during processing.
     • Environmentally controlled processing areas should be maintained to an appropriate cleanliness standard and supplied with air, which has passed through filters of an appropriate efficiency. The suitability of the manufacturing environment should be verified by a documented monitoring program. The frequency of environmental monitoring should be based on the assessment of risk to the product. Records of environmental monitoring should be kept.
311. Dedicated hand-washing facilities should be provided, and where appropriate, near working areas.
312. All persons entering processing areas should wear protective garments appropriate to the operations carried out.
313. Eating, drinking and smoking should be prohibited in processing areas.

Storage areas

314. Storage areas should provide adequate space, suitable lighting, and be arranged and equipped to allow dry, clean and orderly placement of stored material under monitored environmental conditions (e.g. temperature, light, humidity).
315. Storage areas should provide for suitable and effective segregation of quarantined, rejected and released material.
316. If despatch areas are physically different locations from the storage areas, there should be provision for appropriate storage while awaiting transport.
317. Storage facilities should be secured to ensure that quarantined or released product could not be tampered with or removed by unauthorised persons. Product storage facilities should not be used for any other purpose, where this poses a risk to the product.

Equipment

318. Manufacturing equipment should be designed, located and maintained to suit its intended purpose. Equipment should not present any risk to the products. The parts of the equipment that come into contact with the product should be compatible with the product.
319. There should be protocols, which address installation (IQ) and operational (OQ) qualification of equipment and performance qualification (PQ). These protocols should be approved and include the predefined acceptance criteria and the development of procedures for operation, calibration, maintenance, and cleaning. Qualification should be recorded, reviewed and approved prior to use of the equipment.
320. Repair and maintenance operations should not present any hazard to the quality of the products.
321. Manufacturing equipment should be designed so that it can be easily and thoroughly cleaned. It should be cleaned and sterilised if applicable, according to detailed and written procedures and stored under appropriate conditions.
322. Equipment should be uniquely identifiable. This identification should be traceable to all records pertaining to the equipment.
323. Processing equipment should be used according to documented procedures.
324. There should be contingency plans in place for instances where routine equipment cannot be used. In such instances, the contingency plan equipment should meet the same acceptance criteria as for routine.
325. Defective equipment should, if possible, be removed from production and quality control areas, or at least be labelled as defective.
326. Actions to be taken when equipment does not meet specified parameters should be documented.
327. Fixed pipe-work for gases and liquids should be labelled to indicate the contents and the direction of flow.
328. Where controlled temperature conditions (including during transport, where appropriate) are required, the environment should be monitored as follows:
     • there should be temperature recording devices, and records kept and reviewed;
     • there should be an alarm to indicate that a temperature control system has failed. The system should permit resetting only by authorised personnel, and should be checked at regular defined intervals.
329. Water systems used in the manufacturing should be sanitised according to written procedures. The quality of water should be monitored to ensure that it meets specification for its intended purpose.

Maintenance and cleaning

330. Documented cleaning procedures for premises and equipment should be established, implemented and maintained. The following should be included:
     • the cleaning frequency;
     • the materials and equipment to be used;
     • records of cleaning should be maintained;
     • the use of only appropriate specified disinfectants;
     • the specific requirements for different equipment and surfaces; and
     • the dilution and the date of expiry of cleaning agents.
331. Cleaning agents should be selected on the basis of their suitability for intended use.
332. Washing and cleaning of equipment should be chosen and used in order not to be a source of contamination. Cleaning equipment, which generates contamination such as particles, dust or aerosols should be avoided.
333. Where the removal of traces of material or product is important to minimise risk, cleaning methods should be validated.
334. Equipment already in use, which has been moved to another location, taken out of service, modified or undergone major repairs should be re-qualified before re-entry into service.
335. Equipment designed or designated to be portable should be used in accordance with the manufacturer's instructions and should have the necessary operational checks carried out before each period of use.
336. Preventive maintenance should be carried out on premises, facilities and equipment at defined regular intervals.
337. Measuring, weighing, recording and control equipment should be calibrated and checked at defined intervals by appropriate methods. The accuracy of calibration equipment should be assured. Adequate records of calibration and checks should be maintained.

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