4. Buildings and Facilities
Buildings and facilities used in the manufacture of intermediates and APIs should be located, designed, and constructed to facilitate cleaning, maintenance, and operations as appropriate to the type ans stage of manufacture. Facilities should also be designed to minimize potential contamination. Facilities should also be designed to limit exposure to objectionable microbiological contaminants as appropriate.
The flow of materials and personnel through the building or facilities should be designed to prevent mix-ups or contamination.
The washing and toilet facilities should be separate from, but easily accessible to, manufacturing areas.
Laboratory areas/operations should normally be separated from production areas.
All utilities that could impact on product quality (steam, gases, compressed air, and heating, ventilation and air conditioning,...) should be qualified and appropriately monitored. Drawings for theses utility systems should be available.
Adequate ventilation, air filtration and exhaust systems should be provided, where appropriate.These systems should be designed and constructed to minimise risks of contamination and cross-contamination. Particular attention (control air pressure, dust, humidity, temperature...) should be given to areas where APIs or active substance are exposed to the environment.
If air is recirculated to production areas, appropriate measures should be taken be given to control risks of contamination and cross-contamination.
Permanently installed pipework should be appropriately identified.
Water used in the manufacture of APIs or Active substance should be demonstrated to be suitable for its intended use.
Where water used in the process is treated by the manufacturer to achieve a defined quality, the treatment process should be validated and monitored with appropriate action limits.
Adequate lighting should be provided in all areas to facilitate cleaning, maintenance, and proper operations.
Dedicated production areas, which can include facilities, air handling equipment, treatment water and/or process equipment, should be employed in the production of highly sensitizing materials.
Appropriate measures should be established and implemented to prevent cross-contamination from personal, materials, etc. moving from one dedicated area to another.
Sewage, refuse, and other waste (e.g., solids, liquids, or gaseous by-products from manufacturing) in and from buildings and the immediate surrounding area should be disposed of in a safe, timely, and sanitary manner. Containers and/or pipes for waste material should be clearly identified.
Buildings used in the manufacture of intermediates and APIs or active substance should be properly maintained and repaired and kept in a clean condition.
Written procedures should be established assigning responsibility for sanitation and describing the cleaning schedules, methods equipment, and materials to be used in cleaning buildings and facilities.
5. Process Equipment
5. Process Equipment
Equipment used in the manufacture of intermediates and APIs should be of appropriate design and adequate size, and suitably located for its intended use, cleaning, sanitization (where appropriate)n and maintenance.
P.e: in solid dose processing/manufacturing (handling, granulation,tableting, capsule filling, capsule banding, checkweighing....), aseptic processing&freeze drying, primary and secondary packaging.
Equipment should be constructed so that surfaces that contact raw materials.intermediates, or APIs do not alter the quality of the intermediates and APIs beyond the official or other established specifications.
Major equipment (e.g reactors, storage containers, millers,..)and permanently installed processing lines use during the production of an intermediate or API should be appropriately identified.
Any substances associated with the operation of equipment, such as lubricants, heating fluids or coolants, should not contact intermediates or APIs so as to alter their quality beyond the official or other established specifications. Wherever possible, food grade lubricants and oils should be used. (p.e lubricant classification NSF-H1 - National Sanitation Foundation, H1= General incident contact).
Closed or contained equipment should be used wherever appropriate. Where open equipment is used, or equipment is opened, appropriate precautions should be taken to minimize the risk of contamination.
A set of current drawings should be maintained for equipment and critical installations (e.g., instrumentation and utility systems).
Schedules and procedures (including assignment of responsibility) should be established for the preventive maintenance equipment (PM).
Written procedures should be established for cleaning of equipment and its subsequent release for use in the manufacture of intermediates and APIs.Cleaning procedures should contain sufficient details to enable operators to clean each type of equipment in a reproducible and effective manner.
Control, weighing, measuring, monitoring and test equipment that is critical for assuring the quality of intermediates or APIs should be calibrated according to written procedures and an established schedule.
GMP related computerized systems should be validated. Appropriate installation qualification and operational qualification should demonstrate the suitability of computer hardware and software to perform assigned tasks.
Major equipment (e.g reactors, storage containers, millers,..)and permanently installed processing lines use during the production of an intermediate or API should be appropriately identified.
Any substances associated with the operation of equipment, such as lubricants, heating fluids or coolants, should not contact intermediates or APIs so as to alter their quality beyond the official or other established specifications. Wherever possible, food grade lubricants and oils should be used. (p.e lubricant classification NSF-H1 - National Sanitation Foundation, H1= General incident contact).
Closed or contained equipment should be used wherever appropriate. Where open equipment is used, or equipment is opened, appropriate precautions should be taken to minimize the risk of contamination.
A set of current drawings should be maintained for equipment and critical installations (e.g., instrumentation and utility systems).
Schedules and procedures (including assignment of responsibility) should be established for the preventive maintenance equipment (PM).
Written procedures should be established for cleaning of equipment and its subsequent release for use in the manufacture of intermediates and APIs.Cleaning procedures should contain sufficient details to enable operators to clean each type of equipment in a reproducible and effective manner.
Control, weighing, measuring, monitoring and test equipment that is critical for assuring the quality of intermediates or APIs should be calibrated according to written procedures and an established schedule.
GMP related computerized systems should be validated. Appropriate installation qualification and operational qualification should demonstrate the suitability of computer hardware and software to perform assigned tasks.