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According to the requirements of Notice on printing and distributing the development and revision plan on engineering construction standards and codes in 2013 (JIANBIAO [2013] No.6) issued by the Ministry of Housing and Urban-Rural Development of the People's Republic of China, the drafting group has formulated this standard through extensive investigation and study, careful drawing of experience from practices, and reference to relevant international and foreign advanced standards and on the basis of widely soliciting for opinions.
The main technical contents of the standard covers general provisions, terms, environmental specification of production area, location selection and general layout of plant, process design, process piping, process equipment, architecture, air purification, water supply and drainage, and electric.
The provisions printed in bold type in this standard are compulsory and must be enforced strictly.
The Ministry of Housing and Urban-Rural Development of the People’s Republic of China is in charge of the administration of this standard; China Pharmaceutical Association of Engineering Design is responsible for the routine management; and SINOPEC Shanghai Engineering Co., Ltd. is responsible for the explanation of specific technical contents. In case of any comment or suggestion during the process of implementing this standard, please send it to SINOPEC Shanghai Engineering Co., Ltd. (address: No. 769, Zhangyang Road, Shanghai 200120, China).
Standard for design of pharmaceutical industry clean room
1 General provisions
1.0.1 This standard is formulated with a view to implementing the relevant national policies of China in the design of pharmaceutical industry clean room, so as to ensure advanced technology, safety and reliability, quality, energy conservation and environmental protection.
1.0.2 This standard is applicable to the design of constructed, extended and renovated pharmaceutical industry clean room. Production and quality inspection facilities for biological products, toxic pharmaceuticals, psychotropic pharmaceuticals, narcotic pharmaceuticals and radioactive pharmaceuticals shall comply with the relevant regulatory provisions of the China in addition to this standard.
1.0.3 The design of pharmaceutical industry clean roomy shall create necessary conditions for construction and installation, system facility qualification, maintenance management, repair testing, and safe operation.
1.0.4 The design of pharmaceutical industry clean room shall meet the requirements of the current relevant standards of the China in addition to those of this standard,
2 Terms
2.0.1 pharmaceutical clean room
pharmaceutical production room or a confined space with controlled concentration of airborne particles and microorganisms, as well as such parameters as temperature, humidity, and pressure
2.0.2 pharmaceutical industry clean room
building containing a pharmaceutical clean room, used for pharmaceutical production and quality control
2.0.3 room for cleaning personnel
room in which the personnel are cleaned according to a certain procedure before entering into the clean room
2.0.4 room for cleaning material
room in which the materials are cleaned according to a certain procedure before entering into the clean room
2.0.5 controlled environment
specific area where pollution sources are controlled with specified methods
2.0.6 airborne particles
solid or liquid particles which, for purposes of classification of air cleanliness, suspend in the air with the size of 0.1μm to 1,000μm
2.0.7 microorganisms
bacterial or non-bacterial microscopic biological entities capable of replicating or transferring genetic material
2.0.8 particle concentration
the number of airborne particles per unit volume of air
2.0.9 microorganisms concentration
the number of microorganisms per unit volume of air
2.0.10 air cleanliness
air cleanliness class determined by the numbers of particles and microorganisms of certain particle size per unit volume of air
2.0.11 air pattern
the flow pattern and distribution status of air
2.0.12 unidirectional airflow
approximately parallel controlled airflow passing through the entire section of the clean area at a stable wind speed
2.0.13 non-unidirectional airflow
an airflow distribution in which the air fed into the clean area is mixed with the air in the area inductively
2.0.14 mixed airflow
airflow combining unidirectional and non-unidirectional airflow
2.0.15 airlock
room set up at the access to the pharmaceutical clean room for purpose of blocking airflow outside or from an adjacent room and controlling pressure difference
2.0.16 pass box
window that is set on the partition wall of the pharmaceutical clean room to transfer materials and tools, with casements that cannot be opened at the same time installed on both sides
2.0.17 clean working garment
special working garment used in the pharmaceutical clean room
2.11.18 as-built
completed facility with all powers connected and in operation, but without production equipment, materials or operators
2.0.19 at-rest
the state with all production equipment installed in place, but without production activity or operators on site
2.0.20 in-operation
the facility operates in the specified state at the presence of specified personnel and working in the agreed state
2.0.21 high efficiency particulate air filter
air filter with a capture efficiency of over 99.95% for the particles of most permeable particle size (MPPS) under the rated air volume
2.0.22 process water
water used in the pharmaceutical production process, including drinking water, purified water, and water for injection.
2.0.23 purified water
water for medicinal purposes without any additive, prepared by distillation, ion exchange, reverse osmosis or other suitable methods, with the quality conforming to the provisions under purified water in the current Pharmacopoeia of the People's Republic of China
2.0.24 water for injection
water produced by distillation of purified water, with the quality conforming to the standard for water for injection stipulated in the current Pharmacopoeia of the People's Republic of China
2.0.25 cleanliness recovery characteristic
the time required when the clean air conditioning system starts to operate at the specified air exchange rate after the pharmaceutical clean room is polluted, until it is recovered to the inherent at-rest standard
2.0.26 recovery time
the time required for the airborne particles in the air to reach the at-rest standard after all the production operations in the pharmaceutical clean room are completed and the operators leave the site
2.0.27 sterile
without living microorganisms
2.0.28 sterile product
preparations and active ingredients with sterility test items listed in statutory pharmaceutical standards
2.0.29 non-sterile product
preparations and active ingredients with no sterility test items listed in statutory pharmaceutical standards
2.0.30 aseptic processing
a method to producing sterile products which must be conducted under aseptic control conditions
2.0.31 core(critical)area of aseptic production
area requiring special protection since the pharmaceuticals and packaging materials in direct contact with them are exposed to the environment during aseptic processing
2.0.32 aseptic processing room
pharmaceutical clean room where sterile production process is used for pharmaceuticals production and the environmental parameters are under strict control
2.0.33 sterilize
the process to make the survival probability (i.e. sterility assurance level, SAL) of microorganisms in the product not higher than 10-6
2.0.34 airborne viable particles
colonies reproduced to a number visible under suitable conditions via special culture medium with the airborne microbial particles in pharmaceutical clean room
2.0.35 sedimental viable particles
colonies reproduced to a number visible under suitable conditions via special culture medium with the living microbial particles in the pharmaceutical clean room collected by a specified method
2.0.36 validation
a series of documented activities to prove that any procedure, method, production process, equipment, material, behavior or system can indeed lead to the expected results according to the principles of the current Good manufacturing practices (GMP)
2.0.37 qualification
a series of activities to prove that the plant, facility and equipment can operate properly and achieve the expected results
3 Environmental specification of the production area
3.1 General requirements
3.1.1 The environmental parameters of the pharmaceutical production area shall comply with the requirements of the current Good manufacturing practices.
3.1.2 Particles and microorganisms shall be taken as the main control objects for the pharmaceutical clean room, and at the meantime, the environmental parameters shall also be specified, such as temperature, humidity, pressure difference, illumination, and noise.
3.1.3 There shall be no peculiar smell and substances that affect the quality of pharmaceutical and human health in the ambient air.
3.2 Specification of design requirement
3.2.1 The division of the air cleanliness classes of the pharmaceutical clean room shall meet the requirements in Table 3.2.1.
Table 3.2.1 Air cleanliness class of pharmaceutical clean room
Cleanliness class Maximum allowable number of airborne particles (pcs/m3)
At-rest In-operation
≥0.5μm ≥5.0μm ≥0.5μm ≥5.0μm
Class A 3,520 20 3,520 20
Class B 3,520 29 352,000 2,900
Class C 352,000 2,900 3,520,000 29,000
Class D 3,520,000 29,000 Not stipulated Not stipulated
3.2.2 In-operation standard for monitoring of environmental microorganisms in pharmaceutical clean rooms shall meet the requirements in Table 3.2.2.
Table 3.2.2 In-operation standard for environmental microorganisms monitoring of pharmaceutical clean room
Cleanliness
class Airborne viable particles
cfu/m3 Sedimental viable particles
(φ90 mm)
cfu/4h Surface microorganisms
Contact (φ55 mm)
cfu/dish 5 finger gloves
cfu/glove
Class A <1 <1 <1 <1
Class B 10 5 5 5
Class C 100 50 25 —
Class D 200 100 50 —
3.2.3 The air cleanliness class of relevant processes of pharmaceutical production and the environmental area shall meet the requirements of the current Good manufacturing practices and Annex A to this standard.
3.2.4 The temperature and humidity design parameters of the pharmaceutical clean room shall meet the following requirements:
1 If pharmaceutical production process and products set special requirements for temperature and humidity, they shall be determined according to the requirements of process and products;
2 If pharmaceutical production process and products set no special requirements for temperature and humidity, the temperature of the clean rooms of air cleanliness Classes A, B and C shall be 20℃ ~ 24℃, and the relative humidity shall be 45% ~ 60%; the temperature of the clean rooms of air cleanliness Class D shall be 18℃ ~ 26℃ and the relative humidity shall be 45% ~ 65%;
3 The temperature of rooms for cleaning and living of personnel shall be 16 ℃ ~ 20 ℃ in winter and 26 ℃ ~ 30 ℃ in summer.
3.2.5 The static pressure difference between clean rooms of different air cleanliness classes and that between clean room and non-clean room shall not be less than 10 Pa, and that between clean room and the outdoor atmosphere shall not be less than 10 Pa.
3.2.6 Lighting of the pharmaceutical clean room shall be set according to production requirements and shall meet the following requirements:
1 The illuminance should be 300 lx for general lighting in main working rooms;
2 The illuminance should be 200 lx for auxiliary working rooms, corridors, airlocks, and rooms for cleaning personnel and materials;
3 Local adjustment may be made as necessary for production posts with special requirements for illuminance.
3.2.7 The noise level (as-built) shall not be greater than 60 dB(A) for pharmaceutical clean rooms with non-unidirectional airflow, and that shall not be greater than 65 dB(A) for pharmaceutical clean rooms with unidirectional airflow and mixed airflow.
Foreword
1 General provisions
2 Terms
3 Environmental specification of the production area
3.1 General requirements
3.2 Specification of design requirement
4 Location selection and general layout of plant
4.1 Location selection
4.2 General layout
5 Process design
5.1 Process layout
5.2 Personnel cleaning
5.3 Material cleaning
5.4 Process water
6 Process piping
6.1 General requirements
6.2 Piping material, valve and fitting
6.3 Piping installation and insulation
6.4 Safety technology
7 Process equipment
7.1 General requirements
7.2 Design and selection
8 Architecture
8.1 General requirements
8.2 Fire protection and evacuation
8.3 Interior decoration
9 Air purification
9.1 General requirements
9.2 Clean air conditioning system
9.3 Air pattern and air supply rate
9.4 Duct and accessories
9.5 Monitoring and control
9.6 Requirements for high-potent pharmaceutical clean room
10 Water supply and drainage
10.1 General requirements
10.2 Water supply
10.3 Drainage
10.4 Fire fighting system
11 Electric
11.1 Power distribution
11.2 Illumination
11.3 Communication
11.4 Electrostatic protection and grounding
Annex A Example of classification of air cleanliness for pharmaceutical clean room
Annex B Maintenance and management of pharmaceutical clean room
Annex C Validation of pharmaceutical clean room
Explanation of wording in this standard
List of quoted standards
