GMP Cleanroom Standards Guidlines: What You Need to Know

What are the GMP standards for cleanroom

  GMP (Good Manufacturing Practice for Drugs) refers to a complete quality management system that ensures the quality of drugs, ranging from the quality of personnel and production operators responsible for guiding drug production, quality control to production plants, facilities, buildings, equipment, warehousing, production processes, quality management, process hygiene, packaging materials and labels, to the storage, sales or recall of finished products. The purpose is to afford maximizing reduction in the risks of contamination, cross contamination,mix-up and error, to ensure that products are consistently produced with intended use and registrations.

GMP Cleanroom Classification:
  GMP cleanroom classification for pharmaceutical production is mainly divided into four levels: Grade A, Grade B, Grade C, and Grade D.
Standard for suspended particles in clean area air:
 

Standard for microbial concentration in cleanroom under operational status: 

  Grade A is used in high-risk operation areas, such as filling area, stopper placement area, open packaging container area and sterile assembly area. The laminar flow area must have uniform air supply into work area, with air velocity at 0.36m/s~0.54m/s.
  Grade B is used as background areas of Grade A area. Its clean class is ISO 5 at rest.
  Grade C and Grade D are used in areas with lower cleanliness requirements during the production of sterile drugs. Grade C is considered ISO 7 at rest and ISO 8 in operation while Grades D equals to ISO 8 at rest.

Recommended operating environment for sterile drug production
Example of production operation for terminally sterilized products:
  Partial Grade A under Grade C background: (1) Filling (sealing) of products with high risk of contamination (products that are prone to bacterial growth, slow filling speed, wide-mouthed bottles, containers that must be exposed for several seconds before being sealed, etc.)

  Grade C: (1) Filling (sealing) of products. (2) Preparation and filtration of products with high risk of contamination (products that are prone to bacterial growth, require a long time to sterilize after preparation, are not prepared in a closed system, etc.). (3) Non-preparation and filling (sealing) of ophthalmic preparations, sterile ointments, sterile suspensions, etc. (4) Final cleaning of packaging materials and containers that come into direct contact with the product.

  Grade D: (1) Capping. (2) Preparation of materials before filling. (3) Preparation (concentrated preparation or preparation in a closed system, etc.) and filtration of products. (4) Final cleaning of packaging materials and containers that come into direct contact with the product.

  Examples of aseptic manufacturing operations for non-terminally sterilized products:
  Partial Grade A under a Grade B background; (1) Operation and transportation of products that are not completely sealed (products before capping), such as filling (sealing), sub-packaging, plugging, capping, etc. (2) Preparation of liquid medicines or products that cannot be sterilized and filtered before filling. (3) Assembly of packaging materials and containers that are in direct contact with products after sterilization, and transportation and storage in an incompletely sealed state. (4) Crushing, screening, mixing, and sub-packaging of sterile raw materials.

  Grade B: (1) Products that are not completely sealed are placed in completely sealed containers for transportation. (2) Packaging materials and containers that are in direct contact with the product are sterilized and placed in completely sealed containers for transportation and storage.

  Grade C: (1) Preparation of liquid medicines or products that can be sterilized and filtered before filling. (2) Filtration of products.

  Grade D: (1) Final cleaning, assembly or packaging, and sterilization of packaging materials and containers that come into direct contact with the product.

Occupancy status of GMP workshop:
  The occupancy status of the GMP pharmaceutical clean room only stipulates “at-rest” and “operational”, and does not involve the as-built state.
  At-rest: All production equipment is installed and ready, but there is no production activity and no operators are present.
  Operational: The state in which all production equipment operates according to the predetermined process mode and a specified number of operators are on site.

Pressure gradient in GMP clean room:
  GMP stipulates that if there are no special requirements, the pressure difference between clean rooms (areas) and non-clean rooms (areas), and between clean rooms (areas) of different cleanliness levels should be greater than or equal to 10Pa. If necessary, the static pressure difference between operating areas with different functions of the same cleanliness level should also maintain an appropriate pressure gradient, which should be greater than or equal to 10Pa, and the pressure difference between the clean room and the outside should be greater than or equal to 15Pa. The operating area with high dust production of penicillin products should maintain a relative negative pressure.

  Self-cleaning time: After the production work is completed, the operators leave the site and after 15-20 minutes of self-cleaning, the cleanliness of the clean room should reach the as-rest class standard.
  The following rooms should be equipped with pressure difference indication devices:
  1.Between rooms of different cleanliness levels.
  2.Between clean and unclean rooms.
  3.Between sterile and non-sterile rooms.
  4.The rooms that need to maintain a certain relative negative pressure.
  5.Air lock for personal and material purification.

 The following rooms should maintain a relative negative pressure:
  1.Rooms where dusts are generated or emitted.
  2.Rooms where organic solvents are used.
  3.Rooms that produce large amounts of toxic, harmful, hot, humid gases and odors.
  4.Rooms for refining, drying, packaging and dispensing of special drugs such as penicillin.
  5.Pathogen operation room (area).
  6.Radioactive drug production area.

Lighting and noise in GMP clean rooms:
  Unless otherwise specified, the illumination in clean room should be ≥300Lx, and that in auxiliary rooms should be ≥150Lx.
  The at-rest noise of the clean room should be ≤65 dB(A) for a unidirectional flow clean room and ≤60 dB(A) for a non-unidirectional flow clean room.

GMP clean room changing requirements:
  Clean rooms (areas) need to have changing rooms of appropriate sizes according to the number of staff.
  Personal outer clothing must not be brought into the dressing rooms leading to Class B or Class C clean areas!  
  Personnel entering the clean production area shall change clothes, wash hands and disinfect according to the operating procedures. The quality, style and wearing method of work clothes shall be consistent with the requirements of production operations and the cleanliness level of the operation area.
  1.Class A/B clean area; Cover all hair and beard with a hood, tuck the hood into the collar, wear a mask, gloves and protective goggles. Wear sterilized foot covers, tuck the pants into the foot covers, and tuck the cuffs into the hand gloves. Work clothes should be sterilized one-piece work clothes.
  2.Class C clean area; hair and beard should be fully covered, and a mask should be worn. Work clothes should be sterile one-piece work clothes or two-piece work clothes, and appropriate shoes or shoe covers should be worn.
  3.Class D clean area; hair and beard should be fully covered, and appropriate work clothes, shoes or shoe covers should be worn.
  The changing procedure should be: first change out of casual clothes in the locker room of the D-level area, put on ordinary work clothes in the D-level area (which should also be clean work clothes), enter the C-level area to change into new one-piece or two-piece clean work clothes, and then enter the B and A areas to change into sterile work clothes.
  The at-rest clean level of the rear section of the dressing room should be the same as that of its corresponding clean area!

Division of GMP clean room air conditioning system:
  A.The air conditioning purification systems of the following rooms should be set up separately
  1.Clean rooms with the same or similar temperature, humidity and cleanliness should be classified into one air conditioning purification system.
  2.Clean rooms with large differences in temperature, humidity and cleanliness, the air conditioning purification systems of rooms with different usage patterns should be set up separately.
  3.Air conditioning and purification systems for rooms where mixing may cause contamination and cross contamination should be set up separately.
  4.The air conditioning and purification systems of laboratories and pharmaceutical production areas should be set up separately.
  5.The air conditioning purification systems for sterility testing, microbial limit testing, antibiotic microbial testing, and radioactive isotope testing should be set up separately.

  B.The air conditioning purification system of the following rooms should be set up independently
  1.The air conditioning and purification system of the raw plasma laboratory should be set up independently and use special equipment.
  2. Grade rooms for producing special-natured drugs, such as highly allergenic drugs, highly toxic microbial products, bacillus products (such as penicillin) and biological products (such as BCG or drugs made from other active microorganisms) should be equipped with independent air conditioning and purification systems.
  3.The room where β-amide structure drugs and sex hormone drugs are produced should be equipped with independent air conditioning purification system.
  4.Rooms where certain hormones, cytotoxic drugs, and highly active chemical drugs are produced should be equipped with independent air conditioning and purification systems.
  5.The room where certain radioactive drugs, anti-tumor drugs and contraceptive drugs are produced should be equipped with independent air conditioning purification system.
  6.The plasma melting area, component separation area and production area after virus inactivation should be separated from each other, and each should be equipped with an independent air conditioning purification system.
  7.Products after plasma virus removal and inactivation should have a dedicated production area and dedicated equipment with an independent air conditioning and purification system.
  8.An air conditioning purification system should be installed in the production areas of contraceptive drugs, highly toxic microorganisms and spore-forming products.

 C.The air conditioning purification system of the following rooms should be a full-exhaust direct airflow current system
  1.The area where toxic bacteria are operated should be equipped with an independent air conditioning purification system, and the system should adopt a full-exhaust direct airflow current system without return air.
  2.Rooms and places where flammable and explosive gases or dust are generated should be equipped with independent air conditioning purification systems.
  3.Rooms and places where highly toxic and serious hazardous substances are produced should be equipped with independent air conditioning purification systems.
  4.Rooms and places where there is a possibility of drug mixing through the system and serious hazards should be equipped with independent air conditioning purification systems.
  5.Rooms and occasions where there is a possibility of cross-contamination through the system and serious consequences should be equipped with independent air conditioning purification systems.

  D.The air conditioning purification system of the following rooms should be a negative pressure system
  1.The air conditioning purification system in the refining, drying and packaging workshops and places for penicillin and highly allergenic drugs should be a negative pressure system.
  2.The air conditioning purification system in workshops and places where highly toxic, pathogenic microorganisms and spore-forming bacteria products are produced should be a negative pressure system.
  3.The air conditioning purification system in workshops and places that generate a large amount of dust and endanger the cleanliness of the adjacent environment should be a negative pressure system.

GMP Validation:
  Validation is a documented activity that proves that any procedure, production process, equipment, material, activity or system can indeed lead to the expected results. The concept of validation is almost ubiquitous in GMP, whether it is the preliminary validation before a process, a procedure or a system is put into use, or the supervisory validation of these processes, procedures and systems after a certain period of use or after changes, or even the tracking validation of the process of drugs after they are launched on the market, all of which are to "turn ideas into reality" and provide a test basis for the implementation of the quality assurance system, so as to provide a solid foundation for quality assurance.

  Validation of GMP workshops and clean air conditioning facilities should include: 
  1.Design Qualification (DQ): Check the design documents and drawings to confirm whether they meet the requirements of GMP and design specifications for plant buildings and air conditioning purification technology.
  2.Installation Qualification (IQ): Confirm that the construction and installation of plant, facilities and equipment meet the design requirements through inspection of construction and installation documents.
  3.Operation Qualification (OQ): Confirm that the operation of the plant, facilities and equipment meets the design requirements through the inspection results of document drawings, single machine trial operation, combined trial operation and adjustment tests.
  4.Performance Qualification (PQ): Through testing, parameter measurement and dynamic monitoring of systems and equipment, confirm that the plant, facilities and equipment can continue to meet the requirements under normal operating methods and process conditions.

GMP Cleanroom Applications:
  GMP certification is applicable to multiple industries, mainly including the following areas:
  1.Pharmaceutical industry （pharmacy cleanroom）
  2.Food industry (food processing cleanroom)
  3.Cosmetics industry 
  4.Medical device industry （mdeical cleanroom）
  5.Biological products industry (biotech cleanroom)

  View More Our Cleanroom Projects in Different Industries:https://www.airkeyx.com/industry-solutions/detail/usa-mobile-modular-pharmacy-cleanroom-project