Basic Principles of GMP
Premises
Pharmaceutical Quality,
Good manufacturing Practice &
Bioequivalence
Kiev, Ukraine
3 - 7 October 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
Part One, 12
World Health Organization
E-mail: hietavam@who.int
WHO - PSM
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
WHO - PSM
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 - 12.8
WHO - PSM
Premises
Principle

Premises must be
located to minimize
risks of crosscontamination; e.g. not
located next to a
malting factory with
high airborne levels of
yeast
Part One, 12.1,
12.4
WHO - PSM
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
WHO - PSM
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
WHO - PSM
Premises
Ancillary Areas

Rest and refreshment rooms

Changing, washing and toilet areas

Maintenance workshops

Animal houses
Part One 12.11 – 12.14
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Premises
Design Principles

Process flow

Material flow

People flow
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Premises
Example of Materials and People Flow
Arrival of goods
Entrance for visitors Entrance for Workers Shipment of goods
QC
Offices
Canteen
Gowning
Incoming
goods
Corridor
Shipping
Corridor
Corridor
Raw
Materials
&
Packaging
Storage
Weighing
Processing
Washing
Filling
Packaging
Finished
Products
Storage
Material Flow
People Flow
Zone: Clean
Zone:
Secondary
Packaging
Zone: Controlled
Machine
Shop
Utilities and Services
Corridor
Waste Treatment
WHO - PSM
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
WHO - PSM
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
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Premises
Weighing areas

Control systems

Environmental controls, dust control

Segregation

Smooth, impervious, durable, easy to clean finishes

Cleaning

Documentation
Part One 12.23
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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
WHO - PSM
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
WHO - PSM
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
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Premises
Cross-contamination
1. Segregated areas
2. Campaign production
3. Airlocks and pressure differentials
4. Treatment of recirculated air
5. Protective clothing
6. Effective cleaning procedures
7. Closed production systems
8. Residue testing
9. Status labelling
Part One 16.12 (a)–(i)
WHO - PSM
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
WHO - PSM
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
WHO - PSM
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
WHO - PSM