Aseptic processing of health care products – Part 1: General requirements (ISO 13408-1:2008)
Abstract
ISO 13408-1:2008 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.
ISO 13408-1:2008 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 of ISO 13408.
DIN EN ISO 13408-1:2013-08 (E)
Aseptic processing of health care products – Part 1: General requirements (ISO
13408-1:2008 + Amd 1:2013 ) (includes Amendment A1:2013)
Contents Page
Introduction …………………………………………………………………………………………………………………………………… 6
1 Scope …………………………………………………………………………………………………………………………….. 8
2 Normative references …………………………………………………………………………………………………….. 8
3 Terms and definitions …………………………………………………………………………………………………….. 9
4 Quality system elements ………………………………………………………………………………………………. 14
4.1 General ………………………………………………………………………………………………………………………… 14
4.2 Assignment of responsibilities ……………………………………………………………………………………… 14
4.3 Calibration ……………………………………………………………………………………………………………………. 14
5 Aseptic process definition ……………………………………………………………………………………………. 15
5.1 General ………………………………………………………………………………………………………………………… 15
5.2 Risk management …………………………………………………………………………………………………………. 15
6 Manufacturing environment ………………………………………………………………………………………….. 17
6.1 General ………………………………………………………………………………………………………………………… 17
6.2 Manufacturing environment design ………………………………………………………………………………. 18
6.3 Layout ………………………………………………………………………………………………………………………….. 19
6.4 Material and personnel flow ………………………………………………………………………………………….. 21
6.5 HVAC system ……………………………………………………………………………………………………………….. 22
6.6 Cleanroom qualification ……………………………………………………………………………………………….. 24
6.7 Utility services and ancillary equipment ……………………………………………………………………….. 24
6.8 Environmental and personnel monitoring programmes …………………………………………………. 24
7 Equipment ……………………………………………………………………………………………………………………. 28
7.1 Qualification …………………………………………………………………………………………………………………. 28
7.2 Maintenance of equipment ……………………………………………………………………………………………. 30
8 Personnel …………………………………………………………………………………………………………………….. 30
8.1 General ………………………………………………………………………………………………………………………… 30
8.2 Training for APA qualification ………………………………………………………………………………………. 31
8.3 Gowning procedures ……………………………………………………………………………………………………. 32
8.4 General employee health ………………………………………………………………………………………………. 33
9 Manufacture of the product …………………………………………………………………………………………… 34
9.1 Attainment and maintenance of sterility ………………………………………………………………………… 34
9.2 Duration of the manufacturing process …………………………………………………………………………. 34
9.3 Aseptic manufacturing procedures ……………………………………………………………………………….. 35
9.4 Cleaning and disinfection of facilities ……………………………………………………………………………. 35
9.5 Cleaning, disinfection and sterilization of equipment …………………………………………………….. 37
10 Process simulation ………………………………………………………………………………………………………. 38
10.1 General ………………………………………………………………………………………………………………………… 38
10.2 Media selection and growth support ……………………………………………………………………………… 39
10.3 Simulation procedures …………………………………………………………………………………………………. 39
10.4 Incubation and inspection of media filled units ……………………………………………………………… 40
10.5 Initial performance qualification ……………………………………………………………………………………. 40
10.6 Periodic performance requalification …………………………………………………………………………….. 41
10.7 Repeat of initial performance qualification ……………………………………………………………………. 42
10.8 Documentation of process simulations ………………………………………………………………………… 42
10.9 Disposition of filled product …………………………………………………………………………………………. 43
11 Test for sterility ……………………………………………………………………………………………………………. 44
11.1 General ……………………………………………………………………………………………………………………….. 44
11.2 Investigation of positive units from tests for sterility …………………………………………………….. 44
Annex A (informative) Example of a flow chart …………………………………………………………………………….. 45
Annex B (informative) Typical elements of an aseptic process definition ……………………………………… 46
Annex C (informative) Examples of specific risks ………………………………………………………………………… 47
Annex D (informative) Comparison of classification of cleanrooms ……………………………………………… 48
Annex E (informative) Specification for water used in the process ……………………………………………….. 49
Annex F (informative) Aseptic processing area ……………………………………………………………………………. 51
Annex ZA (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 90/385/EEC on Active Implantable Medical Devices ………… 52
Annex ZB (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 93/42/EEC on Medical Devices ……………………………………….. 53
Annex ZC (informative) Relationship between this European Standard and the Essential
Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices …………….. 54
Bibliography ……………………………………………………………………………………………………………………………….. 55