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11

MCC PRESENTATION - GMPMCC PRESENTATION - GMP

MANUFACTURINGMANUFACTURING

ENVIRONMENTSENVIRONMENTS

Presented by :Presented by :

Deryck Smith Consulting EngineersDeryck Smith Consulting Engineers

Module 4

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22

GMPGMP Manufacturing EnvironmentsManufacturing Environments

Air Handling SystemsAir Handling Systems

HVAC SystemsHVAC Systems

HHeatingeating

VVentilationentilation

AAirir CConditioningonditioning

ModuleModule 44:: Pressure Cascades &Pressure Cascades &

Building LayoutsBuilding Layouts

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33

GMPGMP

Manufacturing EnvironmentsManufacturing Environments

Topics for this Module:

1. The integration of air conditioning systems andbuilding layouts.

2. The requirements for pressure cascades and howto achieve them.

3. How building finishes and plant componentsaffect facility cleanliness.

4. Pharmaceutical Equipment

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44

Inter-dependenceInter-dependence of Airof Air

Handling SystemHandling System

s & Buildingss & Buildings

Building layouts, Pressure cascades,

Air handling systems andPharmaceutical equipment are all

inter-related.

No one can exist without the other.

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55

What is a PressureWhat is a Pressure

Cascade?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.

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66

What Is the Purpose of aWhat Is the Purpose of a

Pressure Cascade?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)

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77

Air Pressure CascadeAir Pressure Cascade

D i r t y E n v i r o n

A m b i e n t P r e s

1 5 P a P r e s s

D i f f e r e n t i a

L e s s C l e a n E n v i r o

L o w e r P r e s s u r

1 5 P a P r e s s u

D i f f e r e n t i a l

C l e a n e s t E n v i r o n

H i g h e s t R o o m P r

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88

Measuring the Air PressureMeasuring the Air Pressure

CascadeCascadeThe pressure differential over the doorway isThe pressure differential over the doorway ismeasured with a portable magnahelic gauge or micromeasured with a portable magnahelic gauge or micro

manometer.manometer.

Permanently installedgauges are preferred.

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99

Room Pressure & AirRoom Pressure & Air

MovementMovement A room pressure cascade system forces air toA room pressure cascade system forces air to

flow from clean areas to less-clean areas.flow from clean areas to less-clean areas.

Directional air movement helps carry

contaminants away from a critical process.

Air movement, such as laminar flow (UDAF) over

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

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1010

Typical OSD Plant :Typical OSD Plant :

Cross-contamination ProtectionCross-contamination Protection

What should the room pressures be ?

T A B L E T S

C O M P R .

T A B L E T S

C O M P R .

E N C A P S U L A

P R O D U C T I O N C O R R I D O

A I R

L O C K

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

1 5 P a

3 0 P

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1111

Dispensary LayoutDispensary Layout

M A T E R E A L SF R O M W A R E H O U S

W E I G H E D M A TT O P R O D U C T I

S T A G I N G A R E A

W E I G HB O O T H 2

W E I G HB O O T H 1

Is this a good layout ? PIC/S PH 1/97 (Rev.3) #3.3 & 3.12

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1212

Improved DispensaryImproved Dispensary

LayoutLayout

What should the room pressures be ?

P R E - W E I G H

S T A G I N GP O S T - W E I G H

S T A G I N G

W E I G H

B O O T H 1

W E I G H

B O O T H 2

U N I - D I R E C T I O N A L

A I R F L O W

U N I - D I R E C T I O N A L

A I R F L O WM A T E R E A L S

F R O M

W A R E H O U S E

W E I G H E D

M A T E R I A L

P R O D U C T

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

2 0 P

Airflow direction

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1313

Sampling Booth Layout (1)Sampling Booth Layout (1)

SAMPLING

BOOTH

EXTRACT

HOOD

WAREHOUSE

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1515

Sampling Booth Layout (2)Sampling Booth Layout (2)

SAMPLINGBOOTH

UDAF

HOOD

AIR

LOCK

AIRLOCK

Step-over-bench

CHANGE

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1616

Typical Section ThroughTypical Section Through

Sampling BooothSampling BooothR e t u r n a i r S u p p l y a i r

L a m i n a r f l o w

d i s t r i b u t o r

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1818

Ablution Layout 1Ablution Layout 1

Production

Plant

ChangeRoom

ToiletsStaff

Staff

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1919

Ablution Layout 2Ablution Layout 2

Production

Plant

ChangeRoom ToiletsStaff

Staff

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2121

Protective GarmentsProtective Garments

Outside ??Outside ??

It is pointless having

a change room if it

is not used properly

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Sterile Suite Pressure Cascade

= Room Pressure

= ISO Cleanroom Class

T = TurbulentU = Uni-directional

8

FILLING

MAC

HINE

15Pa

AUTO-CLAVES

AUTO-CLAVES

STERILEFILLING RM

FINISHED PRODUCT STAGING

MAT.

A/L

MAT.

A/L

A/L

FORMULATIONROOM

PERSONELA/L

CHANGE

A/L

STERILECHANGE

STERILESTAGING

COMPONENTPREP

6 0 P

5 0 P a

4 0 P a

4 0 P a

2 5 P a

3 0 P a

2 0 P a

2 0 P a

1 5 P a

1 5 P a

1 5 P a

1 0 P a

7

5T

67

5T

5T

6

6

7

8

8

9

5U

6/7

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2323

Product Flow DiagramProduct Flow Diagram

DISPATCH

SECONDARYPACKING

PRIMARYPACKING

DISPENSARY

RAW MAT.RECEIPT PACK. MAT.

RECEIPT

PACK. MATSTORE

MANUFACTURING

GMP ZONE

PRIMARY PACK

MAT. CLEAN DOWN

Wood free zone

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2424

StaffStaffflow Diagramflow Diagram

DISPATCH

SECONDARYPACKING

PRIMARYPACKING

DISPENSARY

RAW MAT.RECEIPT PACK. MAT.

RECEIPT

PACK. MATSTORE

PRODUCTION

STAFF ENTRY CANTEEN

CHANGE

GMPCHANGE

GMP ZONE

PRIMARY PACK

MAT. CLEAN DOWN

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2525

Negative Pressure FacilitiesNegative Pressure Facilities

Required for facilities handling potentRequired for facilities handling potentcompounds such as penicillin & hormones.compounds such as penicillin & hormones.

Special precautions required to prevent productSpecial precautions required to prevent productcontamination from the atmosphere.contamination from the atmosphere.

Exhaust air must be efficiently filtered and safeExhaust air must be efficiently filtered and safefilter handling must be used.filter handling must be used.

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2626

Safe Change FiltersSafe Change Filters

Used for filtering hazardousmaterials:

Dirty filters are removed into a

plastic bag

The bag is automatically sealedat the filter unit housingA 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.

C St d P i illiCase Study Penicillin

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2727

Case Study PenicillinCase Study Penicillin

PlantPlant

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

W E I G H

R O O M

F

IN

IS

H

E

D

G

O

O

D

S

A I R

L O C K

M

A

L

E

A

B

L

U

T

IO

N

S

G R A N U L A T I N G

S Y R U P S

F I L L I N G

S U P E R -

V I S O R

F E M A L E

C H A N G E

M A L E

C H A N G E

F E M A L E

A B L U T I O N S

P A C K I N G

P R O D U C T

S T O R EA / L

M A T

A / L

P A C K I N G

G O O D S

D R Y

P O W D E R

F I L L I N G

T A B L E T

C O M P R E S -

S I O N

S Y R U P S

P R E P A R A T I O N

W A S H

U P

M I X I N G

C A P S U L E

F I L L I N G

S T A G I N G

Add room pressures,

Cleanroom class and

comment on layout

MALE

ABLUT.

LAUNDRY

FINISH.

GOODS

C St d P i illiC St d P i illi

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2828

Case Study PenicillinCase Study Penicillin

PlantPlant

PRODUCTION PASSAGE

-25Pa

-15Pa ROOM PRESSURE RELATIVETO AMBIENTAIR LEAKAGE DIRECTION

LEGEND

WEIGHROOM

-40Pa

F I N I S H E D

G O O D S

AIRLOCK

M A L E

A B L U T I O N S

GRANULATING SYRUPSFILLING

SUPER-

VISOR

FEMALECHANGE

MALECHANGE

FEMALEABLUTIONS

PACKING

PRODUCTSTORE

A/L

MATA/L

PACKINGGOODS

DRYPOWDERFILLING

TABLET

COMPRES-SIONSYRUPSPREPARATION

WASHUP

MIXING

CAPSULEFILLING

STAGING

-40Pa

-35Pa

-30Pa

-30Pa

-35Pa

-25Pa

-15Pa

-30Pa

-20Pa-30Pa

-10Pa -35Pa

-25Pa

-45Pa

-35Pa

-35Pa

-35Pa

-35Pa

-35Pa

-15Pa-25Pa

- 2 5 P

a

- 4 5 P

a

- 2 5 P

a

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2929

Building Finishes: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 someof the Acceptable and Un-acceptable building

finishes.

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3030

Building FinishesBuilding FinishesNot Acceptable Acceptable

PVA Paint Epoxy or Enamel paint

Window sills Flush glazed windows

Exposed pipes Smooth surfaces

Horizontal pipes &services

Concealed services

Open floor drains Hygienic drains

Floor cracks, flakingfloor surfaces

Homogonous sealedfloors epoxy finish orwelded vinyl

Ceiling cracks &joints

Smooth sealedceilings

Exposed, open lightfittings

Flush light fittings

Wooden furniture S/Steel or Melaminefurniture

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3131

Floors / drainsFloors / drains

Tiled Floor

Epoxy Floor

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3232

Poor & Good WindowsPoor & Good Windows

BacteriaC

ity!!!

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3333

Paint FinishPaint Finish

Not only buildingNot only buildingpaintwork must bepaintwork must beconsidered but alsoconsidered but alsoequipmentequipment

Is there anything wrong

with this Tablet Press?

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3434

Building & EquipmentBuilding & Equipment

FinishesFinishes

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3535

Services DistributionServices Distribution

Impossible to clean! Easy to clean!

KKeep a

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3636

Keep aKeep a

BalanceBalance

Dont ignoreDont ignore

buildingbuilding

finishesfinishes

and then gooverboard onstaff dress code.

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3737

Services DistributionServices 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)

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3838

Split UnitSplit Unit

RETURN AIR

SUPPLY AIR

Fan liberates dust

into the air

Condensate drip tray

Cooling Coil

Poor quality

Air filter

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Fluid Bed DrierFluid Bed Drier

Is the quality of the

supply air to the FBD

correct?

What filtration is used?

Is the exhaust air filtered?

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4040

S e r v i c e R o o m

W a r e h o u s e

A

/L

o

c

k

1

A

ir

L

o

c

k

2

A i r S h o w e r

S a m p l i n gR o o o m S e r v i c e C o r r i d o r

( c o n t a i n s V a c u u m & R O w a t e r s u p p l y )

W e i g h i n g T a b l e t 1T a b l e t 2L i q u i d s M i xS o f t g e l C a p

P a c k i n g

E m e r g e n c y

E x i t

C l e a n C o r r i d o r

E q u i p m e n t W a s h

A i r L o c k 3

S t e r i l e e y e d r o p s

d i s p e n s i n g

& a c e p t i c f i l l i n g

2 S t a g ep e r s o n n e l

e n t r y f o r

e y e d r o p s

M a l e

C h a n g e 2

M a l e

C h a n g e 1

F e m a l e

C h a n g e 1

F e m a l e

C h a n g e 2

P a c k e d

G o o d sQ u a r a n t i n e

A i r L o c k 4

P r i m a r y & S e c

P a c k i n g

Group sessionGroup session

Airlock

difi d i hM difi d L t ith

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4141

Modified Layout withModified Layout with

CascadeCascade

S e c o n d a r y

P a c k i n g

3 0 P a

0 P a

2 0 P a 3 0 P a

0 P a0 P a

1 0 P a

1 0 P a 1 0 P a

2 0 P a2 0 P a

4 0 P a

5 0 P a

6 0 P a

5 0 P a

4 0 P a

1 5 P a

1 5 P a

P r i m a r yP a c k i n g

C h a n g e

M A L 3

A i r L o c k

3 0 P a

P o s t

S t a g i n g

3 0 P a

3 0 P a

0 P a

1 5 P a1 5 P a

2 0 P a

2 0 P a

3 0 P a

2 0 P a

0 P a

1 0 P a

S e r v i c e R o o mA i r L o c k 4

P a c k e d

G o o d sQ u a r a n t i n e

F e m a l eC h a n g e 2

F e m a l e

C h a n g e 1

M a l e

C h a n g e 1

M a l eC h a n g e 2

P A L

S t e r i l e e y e d r o p s

d i s p e n s i n g

& a s c e p t i c f i l l i n g

M A L 4

E q u i p m e n t W a s h

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

E x i t

S o f t g e l C a p

P a c k i n gL i q u i d s M i xT a b l e t 2T a b l e t 1

W e i g h

B o o t h

( c o n t a i n s V a c u u m & R O w a t e r s u p p l y )

S e r v i c e C o r r i d o r

S a m p l i n g

R o o o m

A i r S h o w e r

M

A

L

2

M

A

L

1

W a r e h o u s e

MAL = Material Air Lock

PAL = Personnel Air Lock

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Work session: Connect the arrows

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Product Flow DiagramProduct Flow Diagram

F/GDispatch

SecondaryPacking

PrimaryPacking

Sampling A/L

Raw Mat.Store Released

Materials

Pack Mat.Store

PharmaceuticalManufacturing

Primary Pack

Mat. Clean Down

Work session: Connect the arrows

between processes for Product

Flow and Staff Flow

Quarantine

Sampling A/L

SamplingBooth

PrimaryChange room

GMP ChangeRoom

DispensaryPre-Staging

DispensaryPost-Staging

DispensaryWeiigh Booth