Cleanroom Manufacturing Basic Presentation

8/4/2019 Cleanroom Manufacturing Basic Presentation

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MCC PRESENTATION - GMP

MANUFACTURING ENVIRONMENTS

Presented by :

Deryck Smith ConsultingEngineers

Module 1


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GMPMANUFACTURING ENVIRONMENTS

Presentation Outline

Module 1: Introduction to GMP Environments

Module 2: Air Conditioning System ComponentsModule 3: Types & Configurations of AC Systems

Module 4: Pressure Cascades & building Layouts

Module 5: Validation, Qualification & Maintenance


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GMPMANUFACTURING ENVIRONMENTS

Topics for this Module

What makes up the manufacturingenvironment (not just EnvironmentalControl System)

Contamination & cross-contamination

How cleanrooms are defined Levels of Protection


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Module 1: Introduction to GMPManufacturing Environments

The primary objective of manufacturing in anideal GMP environment is that this should leadto a high quality product being produced.

Manufacturing in an ideal environment not onlyleads to better quality products but should alsoresult in :

* Improved production rates.

* Operator comfort, satisfaction and safety.


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Factors Contributing to QualityProducts

Raw Materials

Personnel

Procedures

Validated processes

Equipment

Premises

Environment

PackingMaterials

Validated processes

Equipment

Premises

Environment

The most important!


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Design considerationsfor a manufacturing facility

Prevent

contact

with dust

Prevent

contactwith fumes

Acceptable

comfort

conditions

cross-contamination

Protect from

product

Protect from

ambientcontamination

contamination

Prevent

of staff

Correct

temperature

and humidity

Avoid

dust

discharge

Avoid

fumedischarge

Avoid

effluent

discharge

PERSONNEL

PROTECTION

PRODUCT

PROTECTION

ENVIRONMENT

PROTECTION

GMP MANUFACTURING

ENVIRONMENT

Three primary considerations to be addressed to ensure a safe and

productive manufacturing facility


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The environment comprises aspects such as:

1. Light

2. Temperature

3. Humidity

4. Air movement

5. Microbial contamination

6. Particulate contamination

Uncontrolled environments can lead to:

Product degradation & contamination

Loss of Product & Profit

The manufacturing environment is

critical for product quality

PIC/S PH 1/97 (Rev.3) #3.3 & 3.12


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Contaminants are :

1.Products or substances other thanproduct manufactured

2.Foreign products3.Particulate matter4.Micro-organisms

5.Endotoxins (degraded micro-organisms)

Cross-contamination is a particular case ofcontamination

What are Contaminants ?


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What is Cross-Contamination ?

Definition of Cross-

Contamination

Contamination of a starting material,

or of a product with another startingmaterial or product.

Cross Contamination (1)

PIC/S PH 1/97 (Rev.3) Pg. 134


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From where does Cross-Contaminationoriginate?

1. Poorly designed air handling systems anddust extraction systems2. Poorly operated and maintained air

handling systems and dust extractionsystems

3. Inadequate procedures for personnel andequipment

4. Insufficiently cleaned equipment

Cross Contamination (2)

PIC/S PH 1/97 (Rev.3) # 3.14


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Cross-contamination (3)

Contamination

Contaminantsfrom

Environment& Operators

Contaminantsfrom

Equipment

CrossContamination

ProductfromEnvironment& Operators

Productfrom

Equipment

PIC/S PH 1/97 # 5.10


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Cross-Contamination (4)

Cross-contamination can be minimized by

1. Personnel procedures

2. Adequate premises3. Use of closed production systems4. Adequate, validated cleaning procedures

5. Appropriate Levels of Protection ofproduct6. Correct air pressure cascade


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How are Contaminants Removed?

By efficient filtration of supply air. By dilution of contaminants or flushing

contaminants by supplying adequate airquantities to the room.

More about this later!


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Where Do Contaminants Come From?

Outside air carries dust which is a contaminant

People generate contaminants:We completely shed our outer skin every 24 hrs.

Particles of 0,3 micron & greater are liberated at arate varying between of 100 000 to 10 million per

minuteA person walking will liberate 5000 bacteria/minute

and a single sneeze can produce up to 1 millionbacteria.

The manufacturing process itself can generatecontaminants eg paint off equipment, dustfrom belt drives, etc


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Why All the Concern About Dust?

Typical size relationship between

dust, bacteria and viruses

Virus

(0,006m to 0,03m)

Dust Particle

(0,5m to 500m)

Bacteria

(0,2m to 2m)

Dust Is a Bacteria Carrier


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Particle sizes

Airborne Contaminants


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Removal of Bacteria

As dust is a carrier, dust must becontrolled.

Ambient bacteria is removed by

filtration. Internal bacterial distribution can be

controlled by directional air flow and

air flushing or dilution. Surface bacteria is controlled by

adherence to strict cleaning sops.


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Defining the Environment

What is the manufacturing environment ?

How does the manufacturing environmenteffect contamination and cross-contamination ?

Cleanroom concept


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What Is a Cleanroom ?

A cleanroom is anenvironment where

the particulatecontamination &bacterialcontamination arelimited toprescribed levels.


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How Are Cleanrooms Classified ?


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Controlled Environment Standards

CONTROLLED ENVIRONMENT STANDARDS

BS EN ISO 1 4644-1: 1999, Federal Standard and Approximate Equivalents.

-

-

-

= Uni-directional (Laminar Flow) ** = Maximum number of viable microorganisms permitted per m. Annex 1 # 3

200


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Facility Parameters That NeedTo Be Controlled

Temperature

Humidity

Air Cleanliness

Room Pressure

Air movement

Lighting


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How Clean Should It Be?

Level of Protection Concept

1. Defines environmental requirements

2. Working to defined environments helps preventcontamination and cross-contamination

3. Allows production under optimal hygiene conditions

4. Takes into account product sensitivity to contamination therapeutic risk


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Many Different Standards In Use

Levels of Protection & Cleanroom Class

definitions currently in use.

EC, PIC/S, TGA, WHO, etc. : A, B, C, D.

US FDA : Critical and Controlled or

Class 100, 1000, etc.

ISPE : Level 1, 2 or 3 or

Cleanroom class (ISO 5, 6, etc.).

Companies : Various others such as White, Grey,Black, Green, etc.


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Therapeutic risks

Manuf

acturingEnvironment

requirement

s

CleanroomClassA/B

Cleanroom

ClassC

Cleanrm.ClassD

Others

Cleanroom Class Required Is Dependant on

Manufacturing Process Being Carried Out !


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Levels of Protection

Parameters to be defined:

1. Air cleanliness requirements (filter typeand position, air changes, air flow

patterns, pressure differentials,contamination levels by particulatematter and micro-organisms)

2. Personnel and material transfer methods3. Permitted operations

4. Building design & finishes


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All operations within a pharmaceutical facilility must becorrelated to well-defined Cleanroom classes.

Example:

ISO 14644-1 ISO5U ISO 5T ISO 7 ISO 8Washing of Containers X

Preparation of solution for terminal sterilization X

Preparation of solutions for aseptic filling X X X

Depyrogenisation of containers X

Filling for terminal sterilization X

Filling for aseptic process X

Etc.

U = Uni-directional

T = TurbulentAnnex 1, # 3, Pg 41


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Based on the Cleanroom Class Requirements,various Levels of Protection have to be created,including:

1. Correlation between process operations and Cleanroom classes2. Type of operation permitted in each Level of Protection zone3. Definition of Cleanroom class (Contaminant parameters, building

materials, room requirements, air handling systems )

4. Requirements for personnel and material in the different classes(clothing, training, type of materials, etc. )

5. Requirements on entry conditions for personnel and material(change & clean-down procedures )



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Parameters Influencing theLevel of Protection (1)

Air Handling

System

Production Room

WithDefined

Requirements

SupplyAir

OutletAir

How does an Air Handling System influencethe Cleanroom Class or Level of Protection ?


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1 Number of particles in the air

2 Number of micro-organisms in the air or onsurfaces

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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Cleanroom Classdefined by

Critical Parameters

Air HandlingSystem

Additional Measures


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Air handling systems: are the main tool for reaching required

parameters

but are not sufficient as such

Need for additional measures such asAppropriate gowning (type of clothing, proper

changingrooms)Validated sanitationAdequate transfer procedures for materials and

personnel

Questions & Answers

Cleanroom Manufacturing Basic Presentation

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