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 Air Handling Systems

Heating Ventilation and Air Conditioning(HVAC) – Part 1 

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

World Health Organization

E mail: hietavam@who.int

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 Air Handling Systems

Objectives

To understand: 

1. The need and reason for pharmaceuticalair handling systems

1. The technical requirements for air handling systems

2. Different types of air handling systems

3. Qualification and monitoring requirements

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 Air Handling Systems

Factors that contribute to quality products:

1.  Starting materials and packaging materials

2.  Validated processes

3.  Personnel

4.  Procedures

5.  Equipment

6.  Design and quality of premises

7.  Manufacturing environment

Inadequacies in the above factors will lead to sub-standard products.

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 Air Handling Systems

The manufacturing environment is critical forproduct quality1.  Light

2.  Temperature

3.  Humidity4.  Air movement

5.  Microbial contamination

6.  Particulate contamination

7.  Uncontrolled environment can lead to product degradation   product contamination

  loss of product and profit 

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 Air Handling Systems

 What are contaminants ?

Contaminants are

1.   Products or substances other than product manufactured

2.   Foreign products

3.   Particulate matter

4.   Micro-organisms

5.   Endotoxins (degraded micro-organisms)Cross-contamination is a particular case of contamination

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 Air Handling Systems

Cross-Contamination (1)

What is Cross-Contamination ?

Definition of Cross-Contamination: 

Contamination of a starting material, intermediate product, or finished product with another starting material or product during production.

(WHO)

Part 1, Glos sary

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 Air Handling Systems

Cross-Contamination (2)

From where does Cross-Contamination originate?

1. Poorly designed air handling systems and dust extractionsystems

2. Poorly operated and maintained air handling systems and dustextraction systems

3. Inadequate procedures for personnel and equipment

4. Insufficiently cleaned equipment 

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 Air Handling Systems

Contamination

Contaminant

from

Environment

Operators

Contaminant

from

Equipment

Cross

Contamination

Product  

from

EnvironmentOperators

Product  

fromEquipment

Cross-Contamination ( 3 )

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 Air Handling Systems

Cross-Contamination (4)

Cross-contamination can be minimized by:

1. Personnel procedures

2. Adequate premises3. Use of closed production systems

4. Adequate, validated cleaning procedures

5. Appropriate levels of protection of product

6. Correct air pressure cascade

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 Air Handling Systems

Level of Protection Concept

1.  Defines environmental requirements

2.

 Helps prevent contamination and cross-contamination

3.  Allows production under optimal hygiene conditions

4.  Takes into account 

  product sensitivity to contamination  therapeutic risk 

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 Air Handling Systems

Therapeutic risks

M an uf   a c

 t   ur i  n gE nvi  r  on

m en t  

r  e q ui  r  em en t   s

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nr  o om  C l   a s sA

 /  B

 C l   e anr  o om  C l   a

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 O t  h  er  s

 

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 Air Handling Systems

Levels of Protection

Parameters to be defined: 

1. Air cleanliness requirements (filters type and position,

air changes, air flow patterns, pressure differentials,contamination levels by particulate matter and micro-organisms)

2. Personnel and material transfer methods

3. Permitted operations4. Building design and finishes Part 3, 9.2, 9.9-9.12

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Levels of Protection

Types of Cleanroom Classes

  International

WHO  A, B, C, D 

  National

  EC, PIC/S, TGA, etc. : A, B, C, D

    US FDA : critical and controlled

    ISPE: level 1, 2 or 3 or cleanroom class

    Companies : various othersPart 3 , 4.1

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Levels of Protection 

All operations within a pharmaceutical facilility must be correlated towell-defined cleanroom classes, and can be included in a hygieneconcept.

Example:

etc.

XFilling for aseptic process

XFilling for terminal sterilisation

XDepyrogenisation of containers

XXXPreparation of solutions for aseptic filling

XPreparation of solution for terminal sterilisation

XWashing of containers

DCBA

Part 3, 4.1

Cleanroom Class

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 Air Handling Systems

Levels of ProtectionBased on the cleanroom class requirements, various Levels of Protectionhave to be created, including:

  Correlation between process operations and cleanroom classes

  Type of operation permitted in each Level of Protection

  Definition of cleanroom class (parameters, building materials,room requirements, HVAC systems)

  Requirements for personnel and material in the different classes

(clothing, training, type of materials, etc.)

  Requirements on entry conditions for personnel and material( change procedures )

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 Air Handling Systems

Parameters influencing Levels of Protection (1) 

Part 3, 4.1

Air Handling

System

Production Room

With

Defined

Requirements

Supply

AirOutlet

Air

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 Air Handling Systems

Parameters influencing Levels of Protection (2)1 Number of particles in the air

2 Number of micro-organisms in the air or on surfaces

3 Number of air changes for each room

4 Air velocity

5 Air flow pattern

6 Filters ( type, position )

7 Air pressure differentials between rooms

8 Temperature, humidity

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 Air Handling Systems

Cleanroom Class

defined by

Critical Parameters

Air HandlingSystemAdditional Measures

Parameters influencing Levels of Protection (3)

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 Air Handling Systems

Parameters influencing Levels of Protection (4)

Air handling systems:

  Are the main tool for reaching required parameters  But are not sufficient as such

  Need for additional measures such as

appropriate gowning (type of clothing, proper changing rooms) 

validated sanitation adequate transfer procedures for materials and personnel