3. PURPOSE OF HVAC?

5. CONTAMINANATS MAY BE

7. CONTAMINATION AND CROSS
CONTAMINATION
Contam
ination
Cross
Contam
ination
Contamina
nt from
Environme
nt &
Operator
Product
from
Environmen
t & Operator
Contamina
nt from
Equipment
Product
from
Equipment

8. 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

9. 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

10. BASIC COMPONENT OF HVAC
 BASIC COMPONENTS OF HVAC
SYSTEM ARE –
 AIR HANDLING UNIT (AHU)
 CHILLER
 DUCTING AND PIPING
 FILTER
 CONTROL SYSTEM

11. BASIC COMPONENT OF AHU
FRESH AIR
PRIMARY
FILTER G 4
BLOWER
COOLING +
HEATING
DEHUMIDIFIERFILTER (EU 7)
FINAL FILTER
EU 13/11
SUPPLY AIR

12. 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

13. HVAC DESIGN
HVAC CAN BE DESIGNED
IN TWO WAYS-
SINGLE USE
RE-CIRCULATED

14. HVAC DESIGN
SINGLE USE – SUPPIED
WITH EXTERNAL AIR WHICH IS
CONDITIONED AND THEN
ENTERS WORKING AREA AND IS
100 % EXTRACTED AND
DISCARDED

15. Schematic flow of
single use design
AHU
WORKING
ROOM
EXHAU
ST
EXFILT
RATIO
N
INFILT
RA
TION
SUPPL
Y AIR
OUTSI
DE AIR

16. 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

17. DIS-ADVANTAGES OF
SINGLE USE
 EXPENSIVE, HIGH RUNNING
COST
 HIGH FILTER LOADING /
FREQUENT CHANGE

18. HVAC -APPLICATION OF
SINGLE USE
 POTENT DRUG FACILITY
 BIO AREA WITH EXPOSURE TO
LIVE PATHOGENIC ORGANISM

19. 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.

20. Schematic flow of
RECIRCULATED
design
AHU
WORKING
ROOM
RETUR
N AIR
EXFILT
RATIO
N
INFILT
RA
TION
SUPPL
Y AIR
MAKE -
UP AIR
INFILT
RA
TION

21. ADVANTAGES OF RE-
CIRCULATED USE
 NORMALLY < FILTER LOAD
 LOWER MAINTENANCE COST
 BETTER FILTRATION
 DECREASED SINGLE USE

22. HVAC –elaboration of HVAC?
H – HIGH
 V – VALUE
 AC – AND COST
 Why invest in
HVAC ?

23. 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

24. 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.

25. 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.

26. 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

27. 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.

28. 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 -

29. AS BUILT CONDITITION
Complete and ready
for operation, with
all services
connected and
functional but
without production
equipment or
operating personnel

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

31. 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

32. HVAC CON NOT ENSURE-
 REMOVE SURFACE
CONTAMINATION
 PROTECTION AGAINST POOR
OPERATOR TECHNIQUE
 EQUIPMENT FAILURE
 KNOWLEDGE OF CONCERNED
PERSNNEL WORKING IN CRITICAL
AREAS.

33. 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.

34. UNIDIRECTIONAL AIR FLOW
Unidirectional
airflow
The operator should
never come between the
air source and the product.

35. AIR PRESSURE DIFFERECE
 Table 4 OF BS 5295 ON
Environmental cleanliness classes
specifies 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.

36. Different environment zones- 1
 For the manufacture of sterile
medicinal products normally 4
Grades can be distinguished.

37. 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.

38. 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.

39. 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.

40. Zone/Grade requirement
Maximum permitted number of
particles/ft^3 equal to or above
Grad
e
At rest In operation
0,5m m
5m m
0,5m m 5m
A
100 0 100 0
B
100 0 10000 70
C
10000 70 100 000 700
D
100 000 700 not defined not defined

41. Examples of operations
for
Grade
T/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.

42. 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

43. Aseptic area behabiourCOUGHING
AND
SNEEZING
IN CLASS
A/B IS
STRICTLY
PROHIBITE
D

44. Gowning in critical area
ENSURE
PROPER
GOWNING
BEFORE
ENTERING
INTO CLASS B
AREA.
OPERATOR
MUST HAVE
EVERYTHING
COVERED.

45. Gowning in critical area
STANDARD
GOWNING FOR
WORKING IN
CLASS A/B AREA
SHOULD
INCLUDE -

46. Personnel: Behavior (MOVEMENT IN
CLEAN ROOM)
Particles >= 0.3µm emitted per
minute !
Personnel
Activity
Snap
Smock
Membrane
Coverall
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.).

47. 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.

48. 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

49. 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

50. Hvac PERFORMANCE CHECKING - 2
TEMPERATURE
RELATIVE HUMIDITY
AIR PRESSURE