hvac and clean room operation (incepta)
TRANSCRIPT
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