Aseptic processing of health care products -Part 1: General requirements
1 Scope
This part of YY/T 0567 specifies the general requirements for, and offers guidance on, processes, programmes and procedures for development, validation and routine control of the manufacturing process for aseptically-processed health care products.
This part includes requirements and guidance relative to the overall topic of aseptic processing. Specific requirements and guidance on various specialized processes and methods related to filtration, lyophilization, clean-in place (CIP) technologies, sterilization in place (SIP) and isolator systems are given in other parts.
Note: This part of YY/T 0567 does not supersede or replace national regulatory requirements, such as Good Manufacturing Practices (GMPs) and/or pharmacopoeial requirements that pertain in particular national or regional jurisdictions.
2 Normative references
The following referenced documents are indispensable for the application of this document. For dated reference, only the edition cited applies. For undated references, the latest edition (including any amendments) applies.
ISO 9001 Quality management systems - Requirements
ISO 11135-1 Sterilization of health care products - Ethylene oxide - Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices
ISO11137-1 Sterilization of health care products - Radiation - Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices
ISO 11137-2 Sterilization of health care products - Radiation - Part 2: Establishing the sterilization dose
ISO 13408-2 Aseptic processing of health care products - Part 2: Filtration
ISO 13408-3 Aseptic processing of health care products - Part 3: Lyophilization
ISO 13408-4:2005 Aseptic processing of health care products - Part 4: Clean-in-place technologies
ISO 13408-5 Aseptic processing of health care products - Part 5: Sterilization in place
ISO 13408-6 Aseptic processing of health care products - Part 6: Isolator systems
ISO 13485 Medical devices - Quality management systems - Requirements for regulatory purposes
ISO 14160 Sterilization of single-use medical devices incorporating materials of animal origin - Validation and routine control of sterilization by liquid chemical sterilants
ISO 14644-1 Cleanrooms and associated controlled environments - Part 1: Classification of air cleanliness
ISO 14644-2 Cleanrooms and associated controlled environments - Part 2: Specifications for testing and monitoring to prove continued compliance with ISO 14644-1
ISO 14644-3 Cleanrooms and associated controlled environments - Part 3: Test methods
ISO 14644-4 Cleanrooms and associated controlled environments - Part 4: Design, construction and startup
ISO 14644-5 Cleanrooms and associated controlled environments - Part 5: Operations
ISO 14644-7 Cleanrooms and associated controlled environments - Part 7: Speparative devices ( clean air hoods, gloveboxes, isolators and mini-environments)
ISO 14698-1 Cleanrooms and associated controlled environments - Biocontamination control - Part 1: General principles and methods
ISO 14698-2 Cleanrooms and associated controlled environments - Biocontamination control - Part 2: Evaluation and interpretation of biocontamination data
ISO 14937 Sterilization of health care products - General requirements for characterization of a sterilizing agent and the development, validation and routine control of a sterilization process for medical devices
ISO 14971 Medical - Devices - Application of risk management to medical devices
ISO 17665-1 Sterilization of health care products - Moist heat - Part 1: Requirements for the development, validation and routine control of a sterilization process for medical devices
ISO 20857 Sterilization of health care products - Dry heat - Requirements for the development, validation and routine control of a sterilization process for medical devices
ICH Guidance for Industry - Q9 Quality Risk Management )
3 Terms and definitions
For the purpose of this document, the following terms and definitions apply.
3.1
action level
established microbial or particulate monitoring results requiring immediate follow-up and corrective action
3.2
airlock
room with interlocked doors designed to maintain pressure control between adjacent rooms of different cleanliness class
3.3
alert level
established microbial or particulate monitoring results giving early warning of potential drift from normal operating conditions which are not necessarily grounds for definitive corrective action but which could require follow-up investigation
3.4
aseptic processing
handling of sterile product, containers and/or devices in a controlled environment, in which the air supply, materials, equipment and personnel are regulated to maintain sterility
Note: This includes sterilization by membrane filtration which cannot be separated from the subsequent aseptic process.
3.5
aseptic processing area(APA)
facilities for aseptic processing (3.4), consisting of several zones
3.6
bioburden
population of viable microorganisms on or in product and/or sterile barrier system
[ISO/TS 11139:2006, 2.2]
Note: For the purposes of aseptic processing, the bioburden of concern is that on or in the product including all factors affecting it such as raw material, intermediates, other components and equipment.
3.7
bio-decontamination
removal of microbiological contamination or its reduction to an acceptable level
[ISO 13408-6:2005, 3.1]
3.8
cleaning
removal of contamination from an item to the extent necessary for further processing or for intended use
[ISO/TS 11139:2006, 2.7]
3.9
combination product
product comprised of drug/device, biologic/device, drug/biologic or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity
3.10
correction
action to eliminate a detected non-conformity
Note: correction may be made in conjunction with corrective action.
[ISO 9000:2005, 3.6.6]
3.11
corrective action
action to eliminate the cause of a detected non-conformity or other undesirable situation
[ISO 9000:2005, 3.6.5]
Note 1: There may be more than one cause for a nonconformity.
Note 2: Corrective action is taken to prevent recurrence whereas preventive action (3.29) is taken to prevent occurrence.
Note 3: There is a distinction between correction and corrective action.
Note 4: Corrective actions might be subject to change control.
3.12
critical processing zone
location within the aseptic processing area in which product and critical surfaces are exposed to the environment
3.13
critical surface
surface that may come into contact with or directly affect a product or its containers or closures
3.14
depyrogentation
validated process designed to remove or deactivate endotoxins
3.15
design qualification
verification that the proposed specification for the facility, equipment or system is suitable for the intended use
[ISO/TS 11139:2006, 2.12]
3.16
direct support zone
protective area directly surrounding a critical processing zone
3.17
disinfectant
chemical agent that is able to reduce the number of viable microorganisms
3.18
disinfection
removal, destruction or de-activation of microorganisms on objects or surfaces
[ISO 14644-5:2004, 3.1.4]
3.19
endotoxin
lipopolysaccharide component of the cell wall of Gram-negative bacteria which is heat stable and elicits a variety of inflammatory responses in animals and humans
3.20
environmental isolates
microorganisms present in and/or isolated from processing or manufacturing environments
Foreword I
Introduction IV
1 Scope
2 Normative references
3 Terms and definitions
4 Quality system elements
5 Aseptic process definition
6 Manufacturing environment
7 Equipment
8 Personnel
9 Manufacture of the product
10 Process simulation
11 Test for sterility
Annex A (Informative) Example of a flow chart
Annex B (Informative) Typical elements of an aseptic process definition
Annex C (Informative) Examples of specific risks
Annex D (Informative) Comparison of classification of cleanrooms
Annex E (Informative) Specification for water used in the process
Annex F (Informative) Aseptic processing area
Bibliography
Aseptic processing of health care products -Part 1: General requirements
1 Scope
This part of YY/T 0567 specifies the general requirements for, and offers guidance on, processes, programmes and procedures for development, validation and routine control of the manufacturing process for aseptically-processed health care products.
This part includes requirements and guidance relative to the overall topic of aseptic processing. Specific requirements and guidance on various specialized processes and methods related to filtration, lyophilization, clean-in place (CIP) technologies, sterilization in place (SIP) and isolator systems are given in other parts.
Note: This part of YY/T 0567 does not supersede or replace national regulatory requirements, such as Good Manufacturing Practices (GMPs) and/or pharmacopoeial requirements that pertain in particular national or regional jurisdictions.
2 Normative references
The following referenced documents are indispensable for the application of this document. For dated reference, only the edition cited applies. For undated references, the latest edition (including any amendments) applies.
ISO 9001 Quality management systems - Requirements
ISO 11135-1 Sterilization of health care products - Ethylene oxide - Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices
ISO11137-1 Sterilization of health care products - Radiation - Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices
ISO 11137-2 Sterilization of health care products - Radiation - Part 2: Establishing the sterilization dose
ISO 13408-2 Aseptic processing of health care products - Part 2: Filtration
ISO 13408-3 Aseptic processing of health care products - Part 3: Lyophilization
ISO 13408-4:2005 Aseptic processing of health care products - Part 4: Clean-in-place technologies
ISO 13408-5 Aseptic processing of health care products - Part 5: Sterilization in place
ISO 13408-6 Aseptic processing of health care products - Part 6: Isolator systems
ISO 13485 Medical devices - Quality management systems - Requirements for regulatory purposes
ISO 14160 Sterilization of single-use medical devices incorporating materials of animal origin - Validation and routine control of sterilization by liquid chemical sterilants
ISO 14644-1 Cleanrooms and associated controlled environments - Part 1: Classification of air cleanliness
ISO 14644-2 Cleanrooms and associated controlled environments - Part 2: Specifications for testing and monitoring to prove continued compliance with ISO 14644-1
ISO 14644-3 Cleanrooms and associated controlled environments - Part 3: Test methods
ISO 14644-4 Cleanrooms and associated controlled environments - Part 4: Design, construction and startup
ISO 14644-5 Cleanrooms and associated controlled environments - Part 5: Operations
ISO 14644-7 Cleanrooms and associated controlled environments - Part 7: Speparative devices ( clean air hoods, gloveboxes, isolators and mini-environments)
ISO 14698-1 Cleanrooms and associated controlled environments - Biocontamination control - Part 1: General principles and methods
ISO 14698-2 Cleanrooms and associated controlled environments - Biocontamination control - Part 2: Evaluation and interpretation of biocontamination data
ISO 14937 Sterilization of health care products - General requirements for characterization of a sterilizing agent and the development, validation and routine control of a sterilization process for medical devices
ISO 14971 Medical - Devices - Application of risk management to medical devices
ISO 17665-1 Sterilization of health care products - Moist heat - Part 1: Requirements for the development, validation and routine control of a sterilization process for medical devices
ISO 20857 Sterilization of health care products - Dry heat - Requirements for the development, validation and routine control of a sterilization process for medical devices
ICH Guidance for Industry - Q9 Quality Risk Management )
3 Terms and definitions
For the purpose of this document, the following terms and definitions apply.
3.1
action level
established microbial or particulate monitoring results requiring immediate follow-up and corrective action
3.2
airlock
room with interlocked doors designed to maintain pressure control between adjacent rooms of different cleanliness class
3.3
alert level
established microbial or particulate monitoring results giving early warning of potential drift from normal operating conditions which are not necessarily grounds for definitive corrective action but which could require follow-up investigation
3.4
aseptic processing
handling of sterile product, containers and/or devices in a controlled environment, in which the air supply, materials, equipment and personnel are regulated to maintain sterility
Note: This includes sterilization by membrane filtration which cannot be separated from the subsequent aseptic process.
3.5
aseptic processing area(APA)
facilities for aseptic processing (3.4), consisting of several zones
3.6
bioburden
population of viable microorganisms on or in product and/or sterile barrier system
[ISO/TS 11139:2006, 2.2]
Note: For the purposes of aseptic processing, the bioburden of concern is that on or in the product including all factors affecting it such as raw material, intermediates, other components and equipment.
3.7
bio-decontamination
removal of microbiological contamination or its reduction to an acceptable level
[ISO 13408-6:2005, 3.1]
3.8
cleaning
removal of contamination from an item to the extent necessary for further processing or for intended use
[ISO/TS 11139:2006, 2.7]
3.9
combination product
product comprised of drug/device, biologic/device, drug/biologic or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity
3.10
correction
action to eliminate a detected non-conformity
Note: correction may be made in conjunction with corrective action.
[ISO 9000:2005, 3.6.6]
3.11
corrective action
action to eliminate the cause of a detected non-conformity or other undesirable situation
[ISO 9000:2005, 3.6.5]
Note 1: There may be more than one cause for a nonconformity.
Note 2: Corrective action is taken to prevent recurrence whereas preventive action (3.29) is taken to prevent occurrence.
Note 3: There is a distinction between correction and corrective action.
Note 4: Corrective actions might be subject to change control.
3.12
critical processing zone
location within the aseptic processing area in which product and critical surfaces are exposed to the environment
3.13
critical surface
surface that may come into contact with or directly affect a product or its containers or closures
3.14
depyrogentation
validated process designed to remove or deactivate endotoxins
3.15
design qualification
verification that the proposed specification for the facility, equipment or system is suitable for the intended use
[ISO/TS 11139:2006, 2.12]
3.16
direct support zone
protective area directly surrounding a critical processing zone
3.17
disinfectant
chemical agent that is able to reduce the number of viable microorganisms
3.18
disinfection
removal, destruction or de-activation of microorganisms on objects or surfaces
[ISO 14644-5:2004, 3.1.4]
3.19
endotoxin
lipopolysaccharide component of the cell wall of Gram-negative bacteria which is heat stable and elicits a variety of inflammatory responses in animals and humans
3.20
environmental isolates
microorganisms present in and/or isolated from processing or manufacturing environments
Contents of YY/T 0567.1-2013
Foreword I
Introduction IV
1 Scope
2 Normative references
3 Terms and definitions
4 Quality system elements
5 Aseptic process definition
6 Manufacturing environment
7 Equipment
8 Personnel
9 Manufacture of the product
10 Process simulation
11 Test for sterility
Annex A (Informative) Example of a flow chart
Annex B (Informative) Typical elements of an aseptic process definition
Annex C (Informative) Examples of specific risks
Annex D (Informative) Comparison of classification of cleanrooms
Annex E (Informative) Specification for water used in the process
Annex F (Informative) Aseptic processing area
Bibliography
