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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
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

Maija Hietava

E-mail: hietavam@who.int

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Air Handling Systems


Objectives
To understand:
1.

The need and reason for pharmaceutical

air handling systems


1. 2.

The technical requirements for air handling systems 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.
2. 3. 4. 5. 6. 7.

Starting materials and packaging materials


Validated processes Personnel Procedures Equipment Design and quality of premises Manufacturing environment

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

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Air Handling Systems


Factors contributing to quality products
Validated processes Procedures Personnel

Starting materials Equipment

Packing materials Premises Environment

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Air Handling Systems


The manufacturing environment is critical for product quality
1.

Light
Temperature Humidity Air movement Microbial contamination Particulate contamination Uncontrolled environment can lead to product degradation
product contamination loss of product and profit
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2. 3. 4. 5. 6. 7.

Air Handling Systems


What are contaminants ?
Contaminants are
1. 2. 3. 4. 5.

Products or substances other than product manufactured Foreign products Particulate matter Micro-organisms 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, Glossary

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Air Handling Systems


Cross-Contamination (2)
From where does Cross-Contamination originate?
1. 2. 3. 4.

Poorly designed air handling systems and dust extraction systems Poorly operated and maintained air handling systems and dust extraction systems Inadequate procedures for personnel and equipment Insufficiently cleaned equipment

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Air Handling Systems


Cross-Contamination ( 3 )
Contaminant from Environment Operators

Contamination

Contaminant from Equipment

Product from Environment Operators

Cross Contamination

Product from Equipment

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Air Handling Systems


Cross-Contamination (4)
Cross-contamination can be minimized by:
1. 2.

Personnel procedures Adequate premises

3.
4. 5.

Use of closed production systems


Adequate, validated cleaning procedures Appropriate levels of protection of product

6.

Correct air pressure cascade

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Air Handling Systems


Level of Protection Concept
1. 2. 3. 4.

Defines environmental requirements Helps prevent contamination and cross-contamination Allows production under optimal hygiene conditions Takes into account
product sensitivity to contamination

therapeutic risk

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Air Handling Systems

Cleanroom Class A / B Cleanroom Class C Cleanrm. Class D Therapeutic risks Others

Manufacturing Environment requirements

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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 microorganisms) Personnel and material transfer methods Permitted operations Building design and finishes
Part 3, 9.2, 9.9-9.12

2. 3. 4.

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Air Handling Systems


Levels of Protection
Types of Cleanroom Classes

International

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A, B, C, D A, B, C, D critical and controlled level 1, 2 or 3 or cleanroom class

National

Companies :

EC, PIC/S, TGA, etc. : US FDA : ISPE:

various others
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Part 3, 4.1

Air Handling Systems


Levels of Protection All operations within a pharmaceutical facilility must be correlated to well-defined cleanroom classes, and can be included in a hygiene concept. Example:
Cleanroom Class Washing of containers Preparation of solution for terminal sterilisation Preparation of solutions for aseptic filling Depyrogenisation of containers Filling for terminal sterilisation Filling for aseptic process etc. X X X X X X X A B C D X

Part 3, 4.1
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Air Handling Systems


Levels of Protection
Based on the cleanroom class requirements, various Levels of Protection have 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)
Air Handling System

Supply Air

Production Room With Defined Requirements

Outlet Air

Part 3, 4.1

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Air Handling Systems


Parameters influencing Levels of Protection (2)
1 2 3 4 5 6 7

Number of particles in the air


Number of micro-organisms in the air or on surfaces Number of air changes for each room Air velocity Air flow pattern Filters ( type, position ) Air pressure differentials between rooms

Temperature, humidity

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Air Handling Systems


Parameters influencing Levels of Protection (3)

Cleanroom Class defined by Critical Parameters

Air Handling System

Additional Measures

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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

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