MCC PRESENTATION - GMP

MANUFACTURING
ENVIRONMENTS
Module 4
Presented by :

Deryck Smith Consulting Engineers

1
GMP Manufacturing Environments

Air Handling Systems

HVAC Systems
Heating
Ventilation
Air Conditioning

Module 4: Pressure Cascades &

Building Layouts

2
 GMP
Manufacturing Environments

Topics for this Module:

1. The integration of air conditioning systems and

building layouts.
2. The requirements for pressure cascades and how
to achieve them.
3. How building finishes and plant components
affect facility cleanliness.
4. Pharmaceutical Equipment

3
Inter-dependence of Air
Handling Systems & Buildings

•Building layouts, Pressure cascades,

Air handling systems and
Pharmaceutical equipment are all
inter-related.
•No one can exist without the other.

4
What is a Pressure
Cascade?
Pressure Cascade
A process whereby air flows from the cleanest area,
which is maintained at the highest pressure to a less
clean area at a lower pressure.

5
What Is the Purpose of a
Pressure Cascade?

• Helps prevent cross-contamination between adjacent

areas.
•Helps prevent ingress of contaminants from outside.
•Is used to enhance separation between areas of different
cleanliness.

The unit of measurement for pressure is the PASCAL (Pa)

6
Air Pressure Cascade

C le a n e s t E n v ir o n m e n t
H ig h e s t R o o m P r e s s u r e

1 5 P a P r e s s u r e
D i f f e r e n t i a l

L e s s C le a n E n v ir o n m e n t
L o w e r P r e s s u r e

1 5 P a P r e s s u r e
D i f f e r e n t i a l

D ir t y E n v ir o n m e n t
A m b ie n t P r e s s u r e

7
Measuring the Air Pressure
Cascade
The pressure differential over the doorway is
measured with a portable magnahelic gauge or micro
manometer.

Permanently installed
gauges are preferred.

8
 Room Pressure & Air
Movement
• A room pressure cascade system forces air to
flow from clean areas to less-clean areas.

 Air movement, such as laminar flow (UDAF) over

the product, protects the product. (aseptic packing / filling)

 Directional air movement helps carry

contaminants away from a critical process. ∆

9
Typical OSD Plant :
Cross-contamination Protection

T A B L E TT AS B L E T ES N C A P S U L A T I O N
C O M P RC .O M P R .

1 5 P a 1 5 P a 1 5 P a

A I R
L O C K
3 0 P a
P R O D U C T I O N C O R R
1 5 P IaD O R

What should the room pressures be ?

10
Dispensary Layout

W E I G H W E I G H
B O O T H 1 B O O T H 2

S T A G I N G A R E A

M A T E R E A L S W E I G H E D M A T E R E
F R O M W A R E H O U S T O P R O D U C T I O N

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

Is this a good layout ?
11
 Improved Dispensary
Layout

W E IG H
B O O T H 1
2 0 P a 3
P R E - W E IG H
S T A G IN G
P O S T - W E IG H
U N I -D I R E C T I O N A L S T A G IN G
Airflow direction A I R F L O W
M A T E R E A L S W E IG H E D
F R O M M A T E R IA L S
W A R E H O U S E P R O D U C T IO
U N I -D I R E C T I O N A L
A I R F L O W

1 0 P a 2 2 0 P a 3 3 0 P a 4

W E IG H
B O O T H 2

What should the room pressures be ?

12
Sampling Booth Layout (1)
EXTRACT
HOOD

SAMPLING
BOOTH

WAREHOUSE

13
Poor Design Extract
System E x tr a c t a ir

E A H o o d

D o o r
G r ille

S A M P L IN G C U B IC L E o r W E IG H B O O
Section Through Sampling Booth
14
Sampling Booth Layout (2)
UDAF
HOOD
SAMPLING
BOOTH
AIR AIR
LOCK LOCK

CHANGE

Step-over-bench

15
Typical Section Through
Sampling Boooth
S u p p ly a ir R e tu r n a ir

L a m in a r f lo w
d is t r ib u to r

16
 What to Qualify in the
Sampling Booth Suite
• Cleanroom class – ISO 8
• HEPA filter integrity test
• Airflow rates
• UDAF velocity
• Room pressures
• Containment – smoke tests
• Temperatures (< 25°C)
17
Ablution Layout 1

Toilets
Staff
Production
Plant

Change
Staff
Room

18
Ablution Layout 2

Production
Plant

Change
Staff Room Toilets
Staff

19
Change Room Layout

A IR
F A C T O R Y C H A N G E
L O C K
R O O M
T O IL E T S

C A N T E E N

20
Protective Garments
Outside ??

It is pointless having
a change room if it
is not used properly
21
Sterile Suite Pressure Cascade
STERILE
CHANGE 2 0 P a
2 0 P a
5 0 P a 5 T 4 0 P a
4 0 P a
COMPONENT 5T A/L
PREP 5T
3 0 P a 6 6
STERILE STERILE
7 STAGING FILLING RM
6
AUTO- 5U 6

MACHINE
FILLING
CLAVES 1 5 P a 2 0 P a

FORMULATION
ROOM
5T CHANGE
4 0 P a
AUTO- A/L
6 0 P a 4 0 P a
CLAVES 2 5 P a 46/7
0 P a 7
5 T

8
7
MAT. MAT. PERSONEL
A/L 9 A/L 2 0 P a
A/L
1 5 P a 2 0 P a FINISHED PRODUCT STAGING 2 0 P a
1 0 P a 8
1 5 P a 2 0 P a
8

15Pa = Room Pressure

8 = ISO Cleanroom Class

T = Turbulent
U = Uni-directional
Product Flow Diagram

RAW MAT.
Wood free zone
RECEIPT PACK. MAT.
RECEIPT

DISPENSARY

PACK. MAT
STORE

MANUFACTURING

PRIMARY PACK
PRIMARY MAT. CLEAN DOWN
PACKING
GMP ZONE

SECONDARY
PACKING
DISPATCH

23
Staff flow Diagram

RAW MAT. STAFF ENTRY CANTEEN

RECEIPT PACK. MAT.
RECEIPT

DISPENSARY CHANGE
PACK. MAT
GMP STORE
CHANGE
PRODUCTION

PRIMARY PACK
PRIMARY MAT. CLEAN DOWN
PACKING
GMP ZONE

SECONDARY
PACKING
DISPATCH

24
Negative Pressure Facilities

• Required for facilities handling potent

compounds such as penicillin & hormones.
• Special precautions required to prevent product
contamination from the atmosphere.
• Exhaust air must be efficiently filtered and safe
filter handling must be used.

25
Safe Change Filters
Used for filtering hazardous
materials:
•Dirty filters are removed into a
plastic bag
•The bag is automatically sealed
at the filter unit housing
•A new filter is inserted via a
plastic bag and the cover closed
•At no time is the operator or
the atmosphere exposed to the
hazardous powder.
26
Case Study – Penicillin
Plant W A
U P
S H S
P
Y
R
R
E
U
P
P
A
S
R A T I O N
T A B L E T
C O M P R E S -
C A P S U L E S I O N
F I L L I N G
M I X I N G

S Y R U P S
F I L L I N G D R Y S T A G I N G
G R A N U L A T I N G
P O W D E R
F I L L I N G

W E I G H
R O O M

P R O D U C T I O N P A S S A G E

P R O D U C T
S T O R E
A / L

MALE

A B L U T IO N S
ABLUT.
P A C K I N G P A C K I N G

M A L E
M A T G O O D S F E M A L E
A / L A B L U T I O N S

S U P E R -
V I S O R
M A L E
F E M A L E C H A N G E
C H A N G E LAUNDRY
Add room pressures, FINISH.

Cleanroom class and

F IN IS H E D

GOOD
G O O D S

S A I R

comment on layout
L O C K

27
Case Study – Penicillin
Plant
WASH -30Pa TABLET
UP SYRUPS COMPRES-
PREPARATION CAPSULE SION
-40Pa FILLING
MIXING -35Pa
-35Pa

DRY STAGING
-30Pa GRANULATING SYRUPS
FILLING -25Pa POWDER -25Pa
FILLING -30Pa

WEIGH
ROOM
-40Pa

PRODUCTION PASSAGE -15Pa

-20Pa PRODUCT
STORE -30Pa -25Pa
A/L

ABLUTIONS
-45Pa

-25Pa

-25Pa
-45Pa
MALE
PACKING PACKING
MAT GOODS FEMALE
A/L ABLUTIONS
-10Pa -35Pa

SUPER-
VISOR -35Pa
MALE
FEMALE CHANGE
-35Pa CHANGE
LEGEND
-35Pa -35Pa
FINISHED

ROOM PRESSURE RELATIVE

GOODS

-15Pa
TO AMBIENT
AIR -35Pa
AIR LEAKAGE DIRECTION LOCK

-15Pa
-25Pa

28
 Building Finishes:

• In module 1 we discussed the need for all

facility components to complement each other.
• Therefore a good air handling system must
be complemented by a building of good
design and good finishes.
• On the next slide we will be looking at some
of the Acceptable and Un-acceptable building
finishes.

29
Building Finishes
Not Acceptable Acceptable
PVA Paint  Epoxy or Enamel paint 
Window sills  Flush glazed windows 
Exposed pipes  Smooth surfaces 
Horizontal pipes &  Concealed services 
services
Open floor drains  Hygienic drains 
Floor cracks, flaking  Homogonous sealed 
floor surfaces floors – epoxy finish or
welded vinyl
Ceiling cracks &  Smooth sealed 
joints ceilings
Exposed, open light  Flush light fittings 
fittings
Wooden furniture  S/Steel or Melamine 
furniture
30
Floors / drains

Tiled Floor

Epoxy Floor

31
Poor & Good Windows

!!!
ty
Ci
ia
er
ct
Ba

32
Paint Finish…
• Not only building
paintwork must be
considered but also
equipment

Is there anything wrong

with this Tablet Press?

33
Building & Equipment
Finishes

34
Services Distribution

Impossible to clean! Easy to clean!

35
 Keep a
Balance
Don’t ignore
building
finishes…

… and then go
overboard on
staff dress code.
36
Services Distribution

•Where ever possible services should be located

behind wall panels
•Exposed services & pipes are very difficult to
clean & sometimes impossible to clean
•Equipment such as Film Coaters should be
enclosed so that only the front face is in the GMP
area. This makes cleaning much easier.
•Make use of service corridors behind equipment
(but must be under negative pressure)

37
Split Unit
RETURN AIR

Poor quality
Air filter

Cooling Coil

Condensate drip tray

SUPPLY AIR

Fan liberates dust

into the air
38
 Fluid Bed Drier

•Is the quality of the

supply air to the FBD
correct?

•What filtration is used?

•Is the exhaust air filtered?

39
Group session
S a m p l i n g
R o o o m S e r v i c e C o r r i d o r
( c o n t a in s V a c u u m & R O w a t e r s u p p ly )
A i r S h o w e r
Airlock

W a r e h o u s e
W e i g h i n g T a b l e t T 1 a b l e t L2 i q u i d s M i Sx o f t g e l C a p s u l e
A ir L o c k 2

P a c k i n g
A/ Lock 1

C l e a n C o r r i d o r
E m e r g e n c y
E x it

M a l e F e m a l e
2 S t aC g h e a n g eC h2 a n g e 2
S t e r i l e e py ee dr s r o o n p n s e l P r i m a r y & S e c o n d
d i s p e n s ien ng t r y f o r P a c k e d
P a c k i n g
& a c e p t i ce y f ie l ld i nr o g p s G o o d s
A i r L o c k 3
Q u a r a n t i n e

M a l e F e m a l e
C h a n g eC h1 a n g e 1
E q u i p m e n t W a s h A i r L o c k 4
S e r v i c e R o o m

40
Modified Layout with
Cascade 2 0 P a S a m p l i n g
R o o o m 0 P a S e r v i c e C o r r i d o r
3 0 P a ( c o n t a in s V a c u u m & R O w a t e r s u p p ly )
A i r S h o w e r
2 0 P a 3 0 P a
1 0 P a
W e i g h P o s t
B o o t h S t a g i n g S o f t g e l C a p s u l e
W a r e h o u s e
M AL 2 2 0 P a 3 0 P a T a b l e t T 1 a b l e t L2 i q u i d s M i x P a c k i n g
1 5 P a 1 5 P a 3 0 P a
0 P a
A i r L o c k
M A L1

1 5 P a

3 0 P a

C l e a n C o r r i d o r
E m e r g e n c y
E x it

2 0 P a 2 0 P a
P A L
4 0 P a M a l e F e m a l 1e 0 P a
M A L 3 C h a n g eC h2 a n g e 2 S e c o n d a P r ry i m a r y
S t e r i l e e y e d r o p s P a c k i n g P
4 0 P a
a c k i n g
d i s p e n s i n g P a c k e d
& a s c e p t i c f i l l i n g G o o d s
Q u a r a n t i2 n0 P e a 3 0 P a
1 0 P a 1 0 P a
6 0 P a
C h a n gM e a l e F e m a l e
1 5 P a M A L 4
5 0 P a C h a n g eC h1 a n g e 1
E q u i p m e n t 5 0 WP a a s h A i r L o c k 4
S e r v i c e 0 PR a o o m
0 P a

0 P a

MAL = Material Air Lock

PAL = Personnel Air Lock 41
 Work session: Connect the arrows
Product Flow Diagram between processes for Product
Flow and Staff Flow

Raw Mat.
Store Quarantine Released Primary
Materials Change room

Sampling A/L
Sampling A/L
GMP Change
Sampling Room
Pack Mat.
Booth Store
Dispensary
Pre-Staging
Dispensary
Post-Staging
Dispensary
Weiigh Booth Primary Pack
Mat. Clean Down

Pharmaceutical Primary Secondary

Manufacturing Packing Packing
F/G
Dispatch
42
 Work session: Connect the arrows
Product Flow Diagram between processes for Product
Flow and Staff Flow

Raw Mat.
Store Quarantine Released Primary
Materials Change room

Sampling A/L
Sampling A/L
GMP Change
Sampling Room
Pack Mat.
Booth Store
Dispensary
Pre-Staging
Dispensary
Post-Staging
Dispensary
Weiigh Booth Primary Pack
Mat. Clean Down

Pharmaceutical Primary Secondary

Manufacturing Packing Packing
F/G
Dispatch
43