PURPOSE OF HVAC?

CONTAMINANATS MAY BE

CONTAMINATION AND CROSS CONTAMINATION

Contamination

Cross Contamination

Contaminant from

Environment &

Operator

Product from

Environment & Operator

Contaminant from

Equipment

Product from

Equipment

SOURCES OF CROSS/CONTAMINATION

POORLY DESIGNED AIR HANDLING SYSTEM AND DUST EXTRACTION SYSTEM

POORLY OPERATED AND MAINTAINED AHU SYSTEM AND DUST EXTRATION SYSTEM

INADEQUATE PROCEDURE FOR PERSONNEL AND EQUIPMENT MOVEMENT

INSUFFICIENTLY CLEANED EQUIPMENT

INADEQUATE LINE CLEARANCE

CROSS CONTAMINATION CAN BE MINIMIZED BY -

ADEQUATE PREMISES

PERSONNEL PROCEDURE

USE OF CLOSED PRODUCTION SYSTEM

ADEQUATE, VALIDATED CLEANING PROCEDURES

APPROPRIATE MAN AND MATERIAL FLOW

CORRECT AIR BALANCING

BASIC COMPONENT OF HVAC

BASIC COMPONENTS OF HVAC SYSTEM ARE –

AIR HANDLING UNIT (AHU)

CHILLER

DUCTING AND PIPING

FILTER

CONTROL SYSTEM

BASIC COMPONENT OF AHU

FRESH AIRPRIMARY

FILTER G 4BLOWER

COOLING + HEATING

DEHUMIDIFIERFILTER (EU 7)

FINAL FILTER

EU 13/11SUPPLY AIR

SUPPLIED AIR TO A CLEAN ROOM SHOULD

HAVE-CONTROLLED TEMPERATURE

CONTROLLED HUMIDITY

CONTROLLED/DEFINED AIR PRESSURE

SPECIFIED NUMBER OF PARTICLES

SPECIFIED NUMBER OF MICROBIAL COUNTS

SPECIFIED AIR CHANGES

SPECIFIED AIR VOLUME

HVAC DESIGN

HVAC CAN BE DESIGNED IN TWO WAYS-

SINGLE USE

RE-CIRCULATED

HVAC DESIGN

SINGLE USE – SUPPIED

WITH EXTERNAL AIR WHICH IS CONDITIONED AND THEN ENTERS WORKING AREA AND IS 100 % EXTRACTED AND DISCARDED

Schematic flow of single use design

AHU

WORKING ROOM

EXHAUST

EXFILTRATIO

N

INFILTRA

TION

SUPPLY AIR

OUTSIDE AIR

ADVANTAGES OF SINGLE USE

CONTINUOUS SUPPLY OF

FRESH CONDITIONED AIR

SAFE / ONCE THRU HANDLING OF HAZARDOUS AND POTENT MATERIAL, BUT EXHAUST AIR NEEDS TO BE FILTERED

DIS-ADVANTAGES OF SINGLE USE

EXPENSIVE, HIGH RUNNING

COST

HIGH FILTER LOADING / FREQUENT CHANGE

HVAC -APPLICATION OF SINGLE USE

POTENT DRUG FACILITY

BIO AREA WITH EXPOSURE TO LIVE PATHOGENIC ORGANISM

HVAC DESIGN - CONTINUED…….

RECIRCULATED – SUPPLIED WITH EXTERNAL AIR WHICH IS CONDITIONED, THEN ENTERS WORKING AREA AND A SMALL PORTION OF IT (10 – 15%) IS DISCARDED/EXTRACTED WITH THE LARGER 90 – 85 % RECONDITIONED AND RESUPPLIED.

Schematic flow of RECIRCULATED

design

AHU

WORKING ROOM

RETURN AIR

EXFILTRATIO

N

INFILTRA

TION

SUPPLY AIR

MAKE -UP AIR

INFILTRA

TION

ADVANTAGES OF RE-CIRCULATED USE

NORMALLY < FILTER LOAD

LOWER MAINTENANCE COST

BETTER FILTRATION

DECREASED SINGLE USE

HVAC –elaboration of HVAC?

H – HIGH

V – VALUE

AC – AND COST

Why invest in HVAC ?

PURPOSE OF THIS INVESTMENT FOR HVAC?

TO GET WORKING ENVIRONMENT WITHIN SPECIFICATION DURING OPERATION (INCEPTA QA SPEC-WHO & EUGMP)

TO ENSURE THAT APPROPRIATE HVAC SYSTEM IS THERE TO PREVENT CONTAMINATION AND CROSS CONTAMINATION

CLEAN AREA/ROOM

An area with defined environmental control of particulate and microbial contamination, constructed and used in such a way as to reduce the introduction, generation and retention of contaminants within the area.

The air in a clean room is repeatedly filtered to remove dust particles and other impurities.

CLEAN ROOM

Cleanrooms are classified by the cleanliness of their air.

Federal Standard 209 described number of particles ≥ 0.5 micron per cubic foot and this count used to classify the room. Recent 209 E version also accepted a metric nomenclature.

CLASSIFICATION OF CLEANROOMS

There are a number of International Standards defining “Clean Rooms”. These are commonly referenced in the biotechnology, pharmaceutical and other sectors.

· US Federal Std 209E 1992

· EEC cGMP 1989

· France AFNOR 1989

· German VDI 2083 1990

· British BS 5295 1989

· Japan JIS B 9920 1989

· ISO EN 14611-1 1999

Hvac –PERFORMANCE (UN-MANNED - 1)

Contamination level of a given cleanroom is dependent on the particle generating activities going on in the room.

If a room is empty, a very low particle concentration can be achieved, this closely reflects the quality of air supplied by the high efficiency filter.

Hvac –PERFORMANCE (MANNED OR UN-MANNED – 2)

If the room has production equipment in it and operating, there will be a greater particle concentration but the greatest concentrations will occur when the room is in full production.

The classification of the room according to FS 209D may therefore be carried out when the room is thus -

AS BUILT CONDITITION

Complete and ready for operation, with all services connected and functional but without production equipment or operating personnel

AT REST

Complete, with all services functioning and with equipment installed and operable or operating, as specified but without personnel in the facility

IN-OPERATION

In normal operation, with all services functioning and with equipment and personnel, if applicable, present and performing their normal work functions in the facility

HVAC CON NOT ENSURE-

REMOVE SURFACE CONTAMINATION

PROTECTION AGAINST POOR OPERATOR TECHNIQUE

EQUIPMENT FAILURE

KNOWLEDGE OF CONCERNED PERSNNEL WORKING IN CRITICAL AREAS.

UNIDIRECTIONAL AIR FLOW

AN AIRFLOW MOVING IN A SINGLE DIRECTION, IN A ROBUST AND UNIFORM MANNER AND AT SUFFICIENT SPEED TO REPRODUCIBLY SWEEP PARTICLES AWAY FROM THE CRITICAL PROCESSING AND TESTING AREA.

UNIDIRECTIONAL AIR FLOW

Unidirectional airflow

The operator should never come between the

air source and the product.

AIR PRESSURE DIFFERECE

Table 4 OF BS 5295 ON Environmental cleanliness classesspecifies that-

Minimum pressure difference between classified areas and unclassified areas should be 15 Pa.

Between classified area and adjacent areas of lower classification should be 10 Pa.

Different environment zones- 1

For the manufacture of sterile medicinal products normally 4 Grades can be distinguished.

Critical area

A critical area is one in which the sterilized drug product, containers and closures are exposed to environmental conditions that must be designed to maintain product sterility. Activities conducted in such areas include manipulations (e.g., aseptic connections, sterile ingredient additions) of sterile materials prior to and during filling and closing operations.

Different environment zones- 2

Grade A: The local zone for high risk operations, e.g. filling zone, stopper bowls, open ampoules and vials, making aseptic connections. Normally such conditions are provided by a laminar air flow work station. Laminar air flow systems should provide an homogeneous air speed of 0.45 m/s +/- 20% (guidance value) at the working position.

Different environment zones- 3

Grade B: In case of aseptic preparation and filling, the background environment for grade A zone.

Grades C and D: Clean areas for carrying out less critical stages in the manufacture of sterile products.

Zone/Grade requirement

Maximum permitted number of particles/ft^3 equal to or above

Grade

At rest In operation

0,5m m 5m m

0,5m m 5m

A 100 0 100 0

B100 0 10000 70

C10000 70 100 000 700

D100 000 700 not defined not defined

Examples of operations for

GradeT/S Products.A Filling of products, when unusually at risk.

C Preparation of solutions, when unusually at risk. Filling of products.

D Preparation of solutions and components for subsequent filling.

Grade Aseptic preparations. A Aseptic preparation and filling.

C Preparation of solutions to be filtered.

D Handling of components after washing.

Zone Concept in the plant, qa_g/sop/038

Zone A – Class 100 Environment (Uner LAF) for sterile critical operation

Zone B – Class 100 environment surrounding the LAF (sterile background)

Zone C – Class 10000 environment for sterile support/process preparation

Zone D – Class 100000 environment for sterile component preparation and non-sterile general production

Zone E – Controlled zone under AC for Secondary Packing

Zone F – Non Classified Area

Aseptic area behabiourCOUGHING

AND

SNEEZING

IN CLASS

A/B IS

STRICTLYPROHIBITE

D

Gowning in critical areaENSURE

PROPER

GOWNING

BEFORE

ENTERING

INTO CLASS B

AREA. OPERATOR

MUST HAVE

EVERYTHING

COVERED.

Gowning in critical area

STANDARD

GOWNING FOR

WORKING IN

CLASS A/B AREA

SHOULD

INCLUDE -

Personnel: Behavior (MOVEMENT IN

CLEAN ROOM)

Particles >= 0.3µm emitted per minute !

PersonnelActivity

SnapSmock

MembraneCoverall

No Movement 100,000 10

Light Movement 500,000 50

Heavy Movement 1,000,000 100

Change Position 2,500,000 250

Slow Walk 5,000,000 500Note: Light/heavy movement refer to partial body movements (motioning with arm, tapping toes, etc.). Change of position refers to whole body motion (standing up, sitting down, etc.).

Aseptic Technique

Keep the entire body out of the path of unidirectional airflow

Unidirectional airflow design is used to protect sterile equipment surfaces, container-closures, and product. Disruption of the path of unidirectional flow in the critical area can pose a risk to product sterility.

Aseptic Technique

Contact sterile materials only with sterile instruments:

Sterile instruments should be held under Class 100 conditions between uses and placed in sterile containers

Operators should not contact sterile products, containers, closures, or critical surfaces with any part of their gown or gloves

Hvac PERFORMANCE CHECKING -1

AS PER - EN/SOP/053 – PROCEDURE OF PHYSICAL PARAMETERS OF INDOOR AIER OF HVAC SYSTEM FOLLINGS ARE CHECKED –

PARTICLE COUNT

AIR FLOW VISUALIZATION / PATTERN

AIR FLOW RATE

AIR CHANGE

Hvac PERFORMANCE CHECKING - 2

TEMPERATURE

RELATIVE HUMIDITY

AIR PRESSURE