BASIC UNDERSTANDING OF AREA AND ROOM CONDITIONS:

The premises used for warehousing, manufacturing, processing, storage, packaging labeling and testing purposes shall be;

• Compatible with other drug manufacturing operations that may be carried out in the same or adjacent area / section.
• Adequately provided with working space to allow orderly and logical placement of equipment, materials, movement of personnel so as to avoid the risk of mix-up between different categories of drugs or with raw materials, intermediates and in-process material and to avoid the possibilities of contamination and cross- contamination by providing suitable mechanism.
• Designed / constructed / maintained to prevent entry of insects, pests, birds, vermins, and rodents. Interior surface (walls, floors and ceilings) shall be smooth and free from cracks, and permit easy cleaning, painting and disinfection.
• Air-conditioned, where prescribed for the operations and dosage forms under production. The production and dispensing areas shall be well lighted, effectively ventilated, with air control facilities and may have proper Air Handling Units (wherever applicable) to maintain conditions including temperature and, wherever necessary, humidity, as defined for the relevant product. These conditions shall be appropriate to the category of drugs and nature of the operation. These shall also be suitable to the comforts of the personnel working with protective clothing, products handled, and operations undertaken within them in relation to the external environment. These areas shall be regularly monitored for compliance with required specifications.
• Provided with drainage system, as specified for the various categories of products, which shall be of adequate size and so designed as to prevent back flow and/or prevent insets and rodents entering the premises. Open channels shall be avoided in manufacturing areas and, where provided, these shall be shallow to facilitate cleaning and disinfection.
• The walls and floors of the areas where manufacture of drugs is carried out shall be free from cracks and open joints to avoid accumulation of dust. These shall be smooth, washable, covered and shall permit easy and effective cleaning and disinfection. The interior surfaces shall not shed particles. A periodical record of cleaning and painting of the premises shall be maintained.

WAREHOUSING AREA:

• Adequate areas shall be designed to allow sufficient and orderly warehousing of various categories of materials and products like starting and packaging materials, intermediates, bulk and finished products, products in quarantine, released, rejected, returned or recalled, machine and equipment spare parts and change items.
• Warehousing areas shall be designed and adapted to ensure good storage conditions. They shall be clean, dry and maintained with acceptable temperature limits, where special storage conditions are required (ex: temperature, humidity), these shall be provided, monitored and recorded. Storage areas shall have appropriate housekeeping and rodent, pests and vermin control procedures and records maintained. Proper racks, bins and platforms shall be provided for the storage of materials.
• Receiving and dispatch bays shall protect materials and products from adverse weather conditions.
• Where quarantine status is ensured by warehousing in separate earmarked areas in the same warehouse or store, these areas shall be clearly demarcated. Any system replacing the physical quarantine, shall give equivalent assurance of segregation. Access to these areas shall be restricted to authorized persons.
• There shall be a separate sampling area in the warehousing area for active raw materials and excipients. If sampling is performed in any other area, it shall be conducted in such a way as to prevent contamination, cross- contamination and mix-up.
• Segregation shall be provided for the storage of rejected, recalled or returned materials or products. Such areas, materials or products shall be suitably marked and secured. Access to these areas and materials shall be restricted.
• Highly hazardous, poisonous and explosive materials such as narcotics, psychotropic drugs and substances presenting potential risks of abuse, fire or explosion shall be stored in safe and secure areas. Adequate fire protection measures shall be provided in conformity with the rules of the concerned civic authority.
• Printed packaging materials shall be stored in safe, separate and secure areas.
• Separate dispensing areas for β (Beta) lactum, Sex Hormones and Cytotoxic substances or any such special categories of product shall be provided with proper supply of filtered air and suitable measures for dust control to avoid contamination. Such areas shall be under differential pressure.
• Sampling and dispensing of sterile materials shall be conducted under aseptic conditions conforming to Grade A, which can also be performed in a dedicated area within the manufacturing facility.
• Regular checks shall be made to ensure adequate steps are taken against spillage, breakage and leakage of containers.
• Rodent treatments (Pest control) should be done regularly and at least once in a year and record maintained.

PRODUCTION AREA:

• The production area shall be designed to allow the production preferably in uni-flow and with logical sequence of operations.
• In order to avoid the risk of cross-contamination, separate dedicated and self-contained facilities shall be made available for the production of sensitive pharmaceutical products like penicillin or biological preparations with live microorganisms. Separate dedicated facilities shall be provided for the manufacture of contamination causing and potent products such as Beta-Lactum, sex hormones and cytotoxic substances.
• Working and in-process space shall be adequate to permit orderly and logical positioning of equipment and materials and movement of personnel to avoid cross-contamination and to minimize risk of omission or wrong application of any manufacturing and control measures.
• Pipework, electrical fittings, ventilation openings and similar services lines shall be designed, fixed and constructed to avoid creation of recesses. Services lines shall preferably be identified by colours and the nature of the supply and direction of the flow shall be marked/indicated.

ANCILLARY AREAS:

• Rest and refreshment rooms shall be separate from other areas. These areas shall not lead directly to the manufacturing and storage areas.
• Facilities for changing, storing clothes and for washing and toilet purposes shall be easily accessible and adequate for the number of users. Toilets, separate for males and females, shall not be directly connected with production or storage areas. There shall be written instructions for cleaning and disinfection of such areas.
• Maintenance workshops shall be separate and away from production areas. Whenever spares, changed parts and tools are stored in the production area, these shall be kept in dedicated rooms or lockers. Tools and spare parts for use in sterile areas shall be disinfected before these are carried inside the production areas.
• Area’s housing animals shall be isolated from other areas. The other requirements regarding animal houses shall be those as prescribed in Rule 150-C (3) of the Drugs and Cosmetics Rules, 1945 which shall be adopted for production purposes.

QUALITY CONTROL AREA:

• Quality Control Laboratories shall be independent of the production areas. Separate areas shall be provided each for physico-chemical, biological, microbiological or radio-isotope analysis. Separate instrument room with adequate area shall be provided for sensitive and sophisticated instruments employed for analysis.
• Quality Control Laboratories shall be designed appropriately for the operations to be carried out in them. Adequate space shall be provided to avoid mix-ups and cross-contamination. Sufficient and suitable storage space shall be provided for test samples, retained samples, reference standards, reagents and records.
• The design of the laboratory shall take into account the suitability of construction materials and ventilation. Separate air handling units and other requirements shall be provided for biological, microbiological and radioisotopes testing areas. The laboratory shall be provided with regular supply of water of appropriate quality for cleaning and testing purpose.
• Quality Control Laboratory shall be divided into separate sections i.e. for chemical, microbiological and wherever required, biological testing. These shall have adequate area for basis installation and for ancillary purposes. The microbiology section shall have arrangements such as airlocks and laminar air flow workstation, wherever considered necessary.