WHO - PSM

PremisesWorkshop on

GMP and Quality Assurance of HIV products

Shanghai, China28 Feb - 4 March 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: +41.22.791.4730World Health Organization

E-mail: hietavam@who.int

Basic Principles of GMP

Part One, 12

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Premises

Objectives

1. To review general requirements

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Part One, 12.1

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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

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Part One, 12.1, 12.4

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

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Part One, 12.4

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Location Geography, climate, noise and economic factors

Neighbours What do they do? What impact can they have on the business?

Pollution/effluent control

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Part One, 12.3 – 12.9

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Premises should be built to:

Facilitate sanitation.

Be maintained and cleaned easily

Services availability

Protection against entry of insects or other animals

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Part One 12.11 – 12.14

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Ancillary Areas

Rest and refreshment rooms

Changing, washing and toilet areas

Maintenance workshops

Animal houses - isolated

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Premises

Design Principles

Process flow

Material flow

People flow

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Q C

Offices Gowning

Canteen

Incoming goods

Corridor

Corridor

Shipping

Corridor

Packaging

Weighing Processing

Filling

Raw Materials

& Packaging Storage

Washing

Machine

Shop

Finished Products Storage

Corridor Utilities and Services Waste Treatment

PremisesExample 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

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Premises

Part two

Basic Principles of GMP

Part One, 12

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Part One 12.15 – 12.16

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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

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Part One 12.18 –12.22

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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

WHO - PSM

Part One 12.23

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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

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Part One 12.24 – 12.23

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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

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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

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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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Part One 16.12 (a)–(i)

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Cross-contamination1. 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

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Part One 12.28 – 12.30

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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

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Part One 12.31 – 12.32

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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

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Part One 12.33 – 12.36

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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