Premises

1
Basic Principles of GMP
Premises Workshop on GMP and Quality Assurance
of HIV products Shanghai, China 28 Feb - 4 March
2005 Maija Hietava M.Sci.Pharm Quality
Assurance and Safety Medicines, Medicines Policy
and Standards, Health Technology and
Pharmaceuticals Cluster Tel [phone] Fax
41.22.791.4730 World Health Organization E-mail
hietavam_at_who.int
Part One, 12
2
Premises

• Objectives
• 1. To review general requirements

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 - isolated

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
• Importance sometimes underestimated!
• 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 safety issues/national
  legislation
• Printed materials storage security essential

Part One 12.18 12.22
13
Premises

• Weighing areas
• Control systems right product, right quantity
• Environmental controls, dust control
• Segregation
• Smooth, impervious, durable, easy to clean
  finishes
• Cleaning
• Documentation
• AVOID CROSS-CONTAMINATION

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

• Windows should not open to the outside

17
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

18
Premises
Not this

• Finish of Floors, Walls and Ceilings
• Difficult but not impossible to get right,
  smooth, impervious, hard-wearing, easy to clean
  but not bricks, tiles, wood or sliding doors!

19
Premises

• Finish of Floors, Walls and Ceilings
• Much better

20
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)
21
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
22
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
23
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