hvac | slide 1 of 26 may 2006 heating, ventilation and air- conditioning (hvac) part 1 (a):...

HVAC | Slide 1 of 26 May 2006

Heating, Ventilation and Air- Conditioning (HVAC)

Part 1 (a):

Introduction and overview

Supplementary Training Modules on Good Manufacturing Practice

WHO Technical Report Series, No. 937, 2006. Annex 2


HVACHVAC

Objectives

To understand:

The need for HVAC systems (Part 1a)

The role of HVAC in protection:– Product– Personnel– Environment

The role of HVAC in dust control (Part 1b)

HVAC system design and its components (Part 2)

Commissioning, qualification and maintenance (Part 3)

1, 2


HVACHVAC

Introduction and Scope

HVAC systems can have an impact on product quality

It can provide comfortable conditions for operators

The impact on premises and prevention of contamination and cross-contamination to be considered at the design stage

Temperature, relative humidity control where appropriate

Supplement to basic GMP text1, 2


Factors contributing to quality products

Starting materials

Personnel

Procedures

Validated processes

Equipment

Premises

Environment

Packing materials

HVAC


The manufacturing environment is critical for product quality. Factors to be considered include:

1. Light

2. Temperature

3. Relative humidity

4. Air movement

5. Microbial contamination

6. Particulate contamination

Uncontrolled environment can lead to product degradation

product contamination (including cross-contamination)

loss of product and profit

HVAC


What is contamination?

It is "the undesired introduction of impurities (chemical/ microbial/ foreign matter into or on to starting material or intermediate – during sampling, production, packaging or repackaging".

Impurities could include products or substances other than the product manufactured, foreign products, particulate matter, micro-organisms, endotoxins (degraded microorganisms), etc.

HVAC

Glossary


What is Cross-contamination?

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

Cross-contamination can result from, e.g.

1. Poorly designed, operated or maintained air-handling systems and dust extraction systems

2. Inadequate procedures for, and movement of personnel, materials and equipment

3. Insufficiently cleaned equipment

HVAC

Glossary, 4.1.11


Contamination

Contaminant from

EnvironmentOperators

Contaminant from

Equipment

CrossContamination

Productfrom

EnvironmentOperators

Productfrom

Equipment

Cross-Contamination

HVAC


Cross-contamination can be minimized by, e.g.

1. Personnel procedures

2. Adequate premises

3. Use of closed production systems

4. Adequate, validated cleaning procedures

5. Appropriate levels of protection of product

6. Correct air pressure cascade

HVAC


HVACHVAC

The guideline further focuses on three concepts of the system:

Product protection– Contamination– Cross-contamination– Environmental conditions

Personnel protection– Prevent contact– Comfort conditions

Environment protection 2


HVACHVAC

Protection: Product and personnel

Areas where materials and products are exposed, should be classified as "clean areas"

Achievement of clean area classification depends on factors such as:

– Building finishes and structure– Air filtration– Air change rate– Room pressure– Temperature– Relative humidity– Material and personnel flow– Outside environment– Occupancy and type of product

4.1.1 - 4.1.3


HVACHVAC

Air filtration and air change rate should ensure attainment of classification

Air change rate is dependent on factors, e.g.– Level of protection required– Quality and filtration of supply air– Particulates generated– Room configuration– Containment effect– Room heat load– Room pressure

Air change rate normally varies between 6 – 20 air changes per hour

4.1.4 - 4.1.6


HVACHVAC

The classification should be achieved in the state as specified (1):

"As built"– Bare room, without equipment or

personnel

4.1.7 - 4.1.8


HVACHVAC


"At rest"– Equipment may be operating, but

no operators present

4.1.9


HVACHVAC


"In operation"– Normal production process with

equipment and personnel,

– Clean up time validated – normally in the order of 20 minutes

4.1.10


HVACHVAC

Control of contaminants

External contaminants removed through effective filtration

Internal contaminants controlled through dilution and flushing, or displacement airflow

Airborne particulates and level of filtration considered critical

4.1.12 - 4.1.15


Therapeutic risks

Man

ufactu

ring

En

viron

men

t req

uirem

ents

Clean

roo

m C

lass A / B

Clean

roo

m C

lass C

Clean

rm. C

lass D

Oth

ers

HVAC


HVACHVAC

Level of protection and air cleanliness determined according to:

Product to be manufactured

Process to be used

Product susceptibility to degradation

4.1.16


Parameters influencing Levels of Protection

Number of particles in the air, number of microorganisms in the air or on surfaces

Number of air changes for each room

Air velocity and airflow pattern

Filters (type, position)

Air pressure differentials between rooms

Temperature, relative humidity

HVAC


Tools to help achieve the desired Level of Protection

Air Handling System

Production RoomWith

DefinedRequirements

SupplyAir

OutletAir

HVAC


Tools to help achieve the desired Level of Protection (2)

Air-handling system can be the main tool for reaching required parameters

May not be 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

HVAC


Cleanroom Classdefined by

Critical Parameters

Air HandlingSystem

Additional Measures

Tools to help achieve the desired Level of Protection (2)

HVAC


Examples of Levels of Protection

Types of Clean room classes

WHO, EC, PIC/S: A, B, C, D

US FDA: Critical and controlled

ISPE: Level 1, 2 or 3

ISO: Class 5, 6, 7 or 8

HVAC


Particles / m3

0.5µm

US 209Dnon-

metric

US 209E1992

metric

EC cGMPAnnex I

1997

GermanyVDI 2083

1990

UKBS 5295

1989

JapanJIS B 9920

1989

ISO 14644-1

1

3,5 0 2 2

10 M 1

35 1 M 1.5 1 3 3

100 M 2

353 10 M 2.5 2 4 4

1.000 M 3

3.530 100 M 3.5 A, BA= unidirectional

B= turbulent

3 E or F 5 5

10.000 M 4

35.300 1.000 M 4.5 4 G or H 6 6

100.000 M 5

353.000 10.000 M 5.5 C 5 J 7 7

1.000.000 M 6

3.530.000 100.000 M 6.5 D 6 K 8 8

10.000.000 M 7

Comparing International Cleanroom Classifications

HVAC


HVACHVAC

Examples of levels of protection4.1.16

LevelConditionExample of area

Level 1GeneralArea with normal housekeeping, e.g. warehouse

Level 2ProtectedArea where steps are taken to protect exposed material/product, e.g. dispensing

Level 3ControlledArea with defined, controlled, monitored environmental conditions to prevent contamination and degradation


All operations within a pharmaceutical facilility should be correlated to well-defined clean room classes, and can be included in a hygiene concept.

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

DCBACleanroom Class

HVAC

hvac | slide 1 of 26 may 2006 heating, ventilation and air- conditioning (hvac) part 1 (a):...

Documents

hvac glossary slide

profit hvac slide

hvac introduction

role of hvac

hvac objectives

scope hvac systems

air conditioning hvac

contamination contaminant