EN 13824:2004
Superseded
A superseded Standard is one, which is fully replaced by another Standard, which is a new edition of the same Standard.
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Sterilization of medical devices - Aseptic processing of liquid medical devices - Requirements
01-06-2011
EN ISO 13408-2:2018
EN ISO 13408-1:2015
EN ISO 13408-3:2011
EN ISO 13408-4:2011
EN ISO 13408-5:2011
24-11-2004
Foreword
Introduction
1 Scope
2 Normative references
3 Terms and definitions
4 Quality management systems
5 Personnel
5.1 Personnel management
5.2 Training for APA qualification
5.3 General employee health
5.4 Monitoring of personnel
5.5 Gowning
5.5.1 Gowning training
5.5.2 Gowning requirements
5.5.3 Control of gowned personnel
6 Premises
7 Process-related media
7.1 Water
7.1.1 Potable water
7.1.2 Treated potable water
7.1.3 Purified water
7.1.4 Water for Injections (WFI)
7.2 Other media
7.2.1 Vacuum systems
7.2.2 Gases
7.2.3 Clean steam
8 Qualification of equipment and utilities, and process
validation
8.1 General
8.2 Requalification and revalidation
9 Processes
9.1 Cleaning and disinfection of the APA
9.1.1 Disinfectants and cleaning agents
9.1.2 Validation of disinfection procedures
9.1.3 Monitoring of cleaning and disinfection
effectiveness
9.2 Bioburden
9.3 Endotoxins
9.4 Sterilization, assembly and use of filling equipment
and utensils
9.5 Clean in place (CIP)
9.6 Steam in Place (SIP)
9.7 Feeding sterilized container components and product
to the filling line
9.8 Sterile filtration
9.8.1 Pore size rating
9.8.2 Liquid filtration
9.8.3 Gas filtration
9.9 Aseptically-produced suspensions
9.10 Filling process: interventions, rejects
9.11 Freeze drying
9.12 Sealing and final packaging
10 Environmental monitoring and controls
10.1 Particulate monitoring programme
10.2 Microbiological monitoring programme
10.2.1 General
10.2.2 Alert and action levels
10.2.3 Review of data
10.3 Environmental monitoring trend analysis
10.4 Investigations and reports
10.4.1 Investigation action plans
10.4.2 Investigation testing
10.4.3 Investigation report
11 Media fills (process simulation tests)
12 Finished product sterility testing
12.1 General
12.2 Investigation of sterility test positives
12.3 Sampling plans
13 Product release
Annex A (normative) Conventional cleanrooms
A.1 Facility design features
A.2 Facility design review
A.3 Material flow
A.4 Aseptic processing area (APA)
A.5 Critical processing zones
A.6 Other processing zones within the APA
A.7 Support areas outside the APA
A.8 Environmental air systems and controls
A.8.1 Temperature and humidity
A.8.2 Air
A.8.3 HEPA filter integrity
A.8.4 Air handling
A.9 Facility design
A.10 Preparation areas
Annex B (normative) Isolator technology
B.1 Types of isolator
B.1.1 General
B.1.2 Transfer devices used with isolators
B.2 Transfer devices
B.2.1 General
B.2.2 Classification system for transfer devices
B.3 Surrounding area
B.3.1 General
B.3.2 Siting of Isolators
B.4 Gloves, gauntlets, half suits and full suits
B.4.1 General
B.4.2 Use of gloves/gauntlets
B.4.3 Changing gloves/gauntlets
B.4.4 Use of half suits, full suits
B.5 Pressure differentials
B.6 Cleaning of isolators
B.7 Filtration of air in isolators
B.8 Pressure differential
B.9 Air change rate
B.10 Biodecontamination of isolator internal surfaces
by microbicidal gas
B.10.1 Gas contact
B.10.2 Biodecontaminant residuals
B.10.3 Isolator biodecontamination: Validation
B.11 Qualification
B.12 Monitoring
B.12.1 Particulate monitoring
B.12.2 Microbiological monitoring
B.12.3 HEPA filters
B.13 Alarms
B.14 Maintenance and requalification (see also Clause 10)
B.15 Product release
Annex C (informative) Aseptically-prepared suspensions
C.1 General
C.2 Media fill considerations
Annex D (normative) Freeze-drying
D.1 General
D.2 Validation
D.3 Gases used during the freeze-drying process
D.4 Process routing
D.5 Open containers and stoppers
D.6 Transport to freeze-dryer
D.7 Unloading and transport to sealing equipment
D.8 Cleaning and disinfection of freeze dryer
D.9 Biodecontamination of the freeze dryer
D.9.1 Frequency
D.9.2 Methods
D.10 Vent filter system
D.11 Environmental monitoring and controls
D.12 Media fills for freeze-drying
D.13 Maintenance
Annex E (normative) Media fills (process simulation tests)
E.1 Performance qualification
E.2 Performance requalification
E.3 Repeat of performance qualification
E.4 Media fill procedures
E.5 Media selection and growth support
E.6 Incubation and inspection of media filled units
E.7 Acceptance criteria
E.7.1 General
E.7.2 Acceptance criteria tables
E.8 Contamination with media
E.9 Data required for media fills
E.10 Media fill runs for which action levels
are exceeded
E.10.1 Investigation
E.10.2 Further actions
Annex F (informative) Contamination rate calculations for
a given number of media filled units
Annex ZA (informative) Clauses of this European Standard
addressing essential requirements or
other provisions of Council Directive
90/385/EEC relating to active
implantable medical devices
Annex ZB (informative) Clauses of this European Standard
addressing essential requirements or
other provisions of Council Directive
93/42/EEC relating to medical devices
Bibliography
This document specifies requirements for the design and operation of aseptic processing facilities and the validation and routine control of aseptic processes for the preparation of sterile liquid medical devices. It is not applicable to those pharmaceutical products where the requirements of the relevant good manufacturing practices are applicable.NOTEMany of the principles included in this document can be applied to certain aseptically processed sterile solid medical devices.
| Committee |
CEN/TC 204
|
| DevelopmentNote |
Supersedes PREN 13824 (10/2005)
|
| DocumentType |
Standard
|
| PublisherName |
Comite Europeen de Normalisation
|
| Status |
Superseded
|
| SupersededBy | |
| Supersedes |
| Standards | Relationship |
| NF EN 13824 : 2005 | Identical |
| UNE-EN 13824:2005 | Identical |
| BS EN 13824:2004 | Identical |
| PN EN 13824 : 2006 | Identical |
| NBN EN 13824 : 2005 | Identical |
| UNI EN 13824 : 2005 | Identical |
| NEN EN 13824 : 2004 | Identical |
| SN EN 13824 : 2005 | Identical |
| I.S. EN 13824:2005 | Identical |
| NS EN 13824 : 1ED 2005 | Identical |
| DIN EN 13824:2005-02 | Identical |
| 02/560165 DC : DRAFT JAN 2002 | BS EN 556-2 - STERILIZATION OF MEDICAL DEVICES - REQUIREMENTS FOR MEDICAL DEVICES TO BE DESIGNATED 'STERILE' - PART 2: REQUIREMENTS FOR ASEPTICALLY PROCESSED MEDICAL DEVICES |
| EN ISO 14644-4:2001 | Cleanrooms and associated controlled environments - Part 4: Design, construction and start-up (ISO 14644-4:2001) |
| EN ISO 14698-1:2003 | Cleanrooms and associated controlled environments - Biocontamination control - Part 1: General principles and methods (ISO 14698-1:2003) |
| EN 550 : 1994 | STERILIZATION OF MEDICAL DEVICES - VALIDATION AND ROUTINE CONTROL OF ETHYLENE OXIDE STERILIZATION |
| EN ISO 14937:2009 | 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 14937:2009) |
| ISO 14160:2011 | Sterilization of health care products Liquid chemical sterilizing agents for single-use medical devices utilizing animal tissues and their derivatives Requirements for characterization, development, validation and routine control of a sterilization process for medical devices |
| ISO 14698-2:2003 | Cleanrooms and associated controlled environments Biocontamination control Part 2: Evaluation and interpretation of biocontamination data |
| EN 556-2:2015 | Sterilization of medical devices - Requirements for medical devices to be designated 'STERILE" - Part 2: Requirements for aseptically processed medical devices |
| EN 1174-3 : 1996 | STERILIZATION OF MEDICAL DEVICES - ESTIMATION OF THE POPULATION OF MICRO-ORGANISMS ON PRODUCT - GUIDE TO THE METHODS FOR VALIDATION OF MICROBIOLOGICAL TECHNIQUES |
| ISO 14644-2:2015 | Cleanrooms and associated controlled environments Part 2: Monitoring to provide evidence of cleanroom performance related to air cleanliness by particle concentration |
| ISO 13485:2016 | Medical devices Quality management systems Requirements for regulatory purposes |
| ISO 14937:2009 | 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 |
| EN 1174-1 : 1996 | STERILIZATION OF MEDICAL DEVICES - ESTIMATION OF THE POPULATION OF MICRO-ORGANISMS ON PRODUCT - REQUIREMENTS |
| EN 1822-2:2009 | High efficiency air filters (EPA, HEPA and ULPA) - Part 2: Aerosol production, measuring equipment, particle counting statistics |
| ISO 14698-1:2003 | Cleanrooms and associated controlled environments Biocontamination control Part 1: General principles and methods |
| EN 1174-2 : 1996 | STERILIZATION OF MEDICAL DEVICES - ESTIMATION OF THE POPULATION OF MICRO-ORGANISMS ON PRODUCT - GUIDANCE |
| EN 552:1994/A2:2000 | STERILIZATION OF MEDICAL DEVICES - VALIDATION AND ROUTINE CONTROL OF STERILIZATION BY IRRADIATION |
| ISO 13408-1:2008 | Aseptic processing of health care products — Part 1: General requirements |
| EN ISO 14644-5:2004 | Cleanrooms and associated controlled environments - Part 5: Operations (ISO 14644-5:2004) |
| ISO 14644-7:2004 | Cleanrooms and associated controlled environments — Part 7: Separative devices (clean air hoods, gloveboxes, isolators and mini-environments) |
| ISO 10993-1:2009 | Biological evaluation of medical devices Part 1: Evaluation and testing within a risk management process |
| ISO 14644-1:2015 | Cleanrooms and associated controlled environments Part 1: Classification of air cleanliness by particle concentration |
| EN 1822-1:2009 | High efficiency air filters (EPA, HEPA and ULPA) - Part 1: Classification, performance testing, marking |
| EN ISO 14644-2:2015 | Cleanrooms and associated controlled environments - Part 2: Monitoring to provide evidence of cleanroom performance related to air cleanliness by particle concentration (ISO 14644-2:2015) |
| EN 980:2008 | Symbols for use in the labelling of medical devices |
| EN ISO 14644-1:2015 | Cleanrooms and associated controlled environments - Part 1: Classification of air cleanliness by particle concentration (ISO 14644-1:2015) |
| EN ISO 14160:2011 | Sterilization of health care products - Liquid chemical sterilizing agents for single-use medical devices utilizing animal tissues and their derivatives - Requirements for characterization, development, validation and routine control of a sterilization process for medical devices (ISO 14160:2011) |
| EN 554 : 1994 | STERILIZATION OF MEDICAL DEVICES - VALIDATION AND ROUTINE CONTROL OF STERILIZATION BY MOIST HEAT |
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