00/560097 DC : DRAFT JAN 2000

Foreword
1 Introduction
2 Scope
3 Normative references
4 Definitions
5 Quality management systems
6 Personnel
   6.1 Personnel management
   6.2 Training and APA qualification
   6.3 General employee health
   6.4 Monitoring of personnel
   6.5 Gowning training
   6.6 Gowning requirements
   6.7 Control of gowned personnel
7 Premises: conventional cleanrooms
   7.1 Facility design features
   7.2 Facility design review
   7.3 Material flow
   7.4 Aseptic processing area (APA)
   7.5 Critical processing zones
   7.6 Other processing zones
   7.7 Support areas outside the APA
   7.8 Environmental air systems and controls
   7.9 Clean room design
   7.10 Preparation areas
8 Premises: isolator technology
9 Process-related media
   9.1 Water
   9.2 Other media
10 Qualification of equipment and utilities, and process validation
   10.1 General
   10.2 Qualification and validation of processing equipment
   10.3 Validation of sterilization of equipment product
         contact surfaces
   10.4 Qualification and validation of process related utilities
   10.5 Qualification and requalification; validation and
         revalidation
11 Processes
   11.1 Cleaning and disinfection of the APA
   11.2 Bioburden
   11.3 Depyrogenation
   11.4 Sterilization, assembly and use of filling equipment
         and utensils
   11.5 Clean in place (CIP)
   11.6 Steam in place (SIP)
   11.7 Feeding sterilized container components and product
         to the filling line
   11.8 Sterile filtration
   11.9 Aseptically-produced suspensions
   11.10 Filling process: interventions, rejects
   11.11 Freeze drying
   11.12 Sealing and final packaging
12 Environmental monitoring and controls
   12.1 Particulate monitoring programme
   12.2 Microbiological monitoring programme
   12.3 Environmental monitoring trend analysis
   12.4 Investigation and reports
13 Media fills (process simulation tests)
14 Finished product sterility testing
   14.1 General
   14.2 Investigation of sterility test positives
   14.3 Sampling plans
15 Product release
Annex A (Normative) Isolator technology
   A.1 Types of isolator
   A.2 Transfer systems
   A.3 Surrounding premises
   A.4 Gloves, gauntlets, suits and half-suits
   A.5 Pressure differentials
   A.6 Cleaning of isolators
   A.7 Sterilization of internal atmosphere by filtration
   A.8 Pressure differential
   A.9 Air change rate
   A.10 Sterilization of Isolator internal surfaces by
        microbicidal gas
   A.11 Qualification
   A.12 Monitoring
   A.13 Alarms
   A.14 Maintenance and requalification
   A.15 Product release
Annex B (Informative) Aseptically-prepared suspensions
   B.1 General
   B.2 Media fill considerations
Annex C (Normative) Freeze drying
   C.1 General
   C.2 Validation
   C.3 Freeze drying process control parameters
   C.4 Process routing
   C.5 Open containers and stoppers
   C.6 Transport to freeze dryer
   C.7 Unloading and transport to sealing equipment
   C.8 Cleaning and disinfection of freeze dryer
   C.9 Frequency
   C.10 Vent filter system
   C.11 Environmental monitoring and controls
   C.12 Special media fill concerns for freeze drying
   C.13 Maintenance
Annex D (Normative) Media fills (process simulation tests)
   D.1 Initial performance qualification
   D.2 Periodic performance requalification
   D.3 Repeat of initial performance qualification
   D.4 Media fill procedures
   D.5 Media selection and growth support
   D.6 Incubation and inspection of filled media units
   D.7 Acceptance criteria
   D.8 Contamination with media
   D.9 Data required for media fills
   D.10 Media fill runs exceeding action levels
Annex E (Informative) Derivation of contamination rate
        calculations for a given number of media filled units
Annex F (Informative) Bibliography
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