Premises Workshop on GMP and Quality Assurance of TB products Kuala Lumpur Malaysia, 21 – 25 February 2005 Maija Hietava

1. Basic Principles of GMP Premises Workshop on GMP and Quality Assurance of TB products Kuala Lumpur Malaysia, 21 – 25 February 2005 Maija Hietava M.Sci.Pharm Quality Assurance and Safety: Medicines, Medicines Policy and Standards, Health Technology and Pharmaceuticals Cluster Tel: +41.22.791.3598 Fax: +41.22.791.4730 World Health Organization E-mail: hietavam@who.int Part One, 12

2. Premises Objectives 1. To review general requirements 2. To list key requirements for site choice 3. To consider specific requirements for main areas 4. To list major facilities required in a multifunction site

3. Premises Principle Premises must be located, designed, constructed, adapted and maintained for the operations: • Minimize risks of errors and cross-contamination • Permit effective cleaning • Permit effective maintenance • Minimize build-up of dirt and dust • Eliminate any adverse effects on quality Part One, 12.1

4. Premises Principle • Premises must be located to minimize risks of cross-contamination; e.g. not located next to a malting factory with high airborne levels of yeast Part One, 12.1, 12.4

5. Premises Location • Geography, climate, noise and economic factors • Neighbours • What do they do? • What impact can they have on the business? • Pollution/effluent control Part One, 12.4

6. Premises Premises should be built to: • Facilitate sanitation. • Be maintained and cleaned easily • Services availability • Protection against entry of insects or other animals Part One, 12.3 – 12.9

7. Premises Ancillary Areas • Rest and refreshment rooms • Changing, washing and toilet areas • Maintenance workshops • Animal houses Part One 12.11 – 12.14

8. Premises Design Principles • Process flow • Material flow • People flow

9. Premises Example of Materials and People Flow Arrival of goods Entrance for visitors Entrance for Workers Shipment of goods Material Flow People Flow Zone: Clean Zone: Secondary Packaging Zone: Controlled

10. Basic Principles of GMP Premises Part two Part One, 12

11. Premises Warehouse – I • Storage areas of sufficient capacity for all the material • Clean, dry and maintained within acceptable temperature limits • Area under cover, protection from heat, dirt, and rain Part One 12.15 – 12.16

12. Premises Warehouse – II • Areas clearly marked and access limited for quarantine status goods. • QC sampling area with GMP standards • Segregated areas for rejected, recalled and returned materials • Separate areas for highly active, hazardous, narcotic materials • Printed materials storage Part One 12.18 –12.22

13. Premises Weighing areas • Control systems • Environmental controls, dust control • Segregation • Smooth, impervious, durable, easy to clean finishes • Cleaning • Documentation Part One 12.23

14. Premises Manufacturing and Packaging – I • Dedicated and self-contained facilities for: • Highly sensitizing materials (penicillins) • Biological preparations (live microorganisms) • Logical flows of materials and people • Adequacy of working space and orderly and logical positioning of equipment • Interior surfaces smooth/crack-free/easy to clean Part One 12.24 – 12.23

15. Premises Other Areas • Personnel rest areas/cafeterias/changing rooms • away from operating areas • prevention of cross-contamination • prevention of operators going outside in work clothes • provision of access control • prevention of visitors access to operating areas • Maintenance service areas • separated from production areas whenever possible

16. Premises Question no 3 • Design of these is essential for the proper production functions: • Personnel ?? • Material ?? • Production ??

17. Premises Question no 4 • This kind of premises are needed for • Biological products (penicillins) • Highly sensitising preparations (living organisms)

18. Premises Finish of Floors, Walls and Ceilings • Difficult but not impossible to get right • Smooth, impervious, hard-wearing, easy to clean • Resistant to operations and materials in use • Windows not opening to the outside • Avoid sliding doors

19. Premises Cross-contamination • Segregated areas • Campaign production • Airlocks and pressure differentials • Treatment of recirculated air • Protective clothing • Effective cleaning procedures • Closed production systems • Residue testing • Status labelling Part One 16.12 (a)–(i)

20. Premises Manufacturing and Packaging – I • Pipework and other fittings sited to avoid recesses • Drain design: • equipped to prevent backflow • open channels avoided • Effective air handling to suit product • temperature • humidity • filtration • monitoring Part One 12.28 – 12.30

21. Premises Manufacturing and Packaging – II • Specifically designed and laid out to avoid mix-ups and cross-contamination • Changing facilities to provide segregated access • Prevention of cross-contamination • Suitable lighting levels Part One 12.31 – 12.32

22. Premises In-Process and QC laboratories • Located separate from but near manufacturing • prevention of cross-contamination • separate biological , microbiological, radioisotopic areas • Designed for the operations being carried out • suitable storage space Part One 12.33 – 12.36

23. Premises Question no 5 • Main principles of GMP is to eliminate or minimize this in pharmaceutical production.