MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTS

1
MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTS
Module 4

• Presented by
• Deryck Smith Consulting Engineers

2
GMP Manufacturing Environments

• Air Handling Systems
• HVAC Systems
• Heating
• Ventilation
• Air Conditioning
• Module 4 Pressure Cascades
• Building Layouts

3
GMP Manufacturing Environments

• Topics for this Module
• The integration of air conditioning systems and
  building layouts.
• The requirements for pressure cascades and how to
  achieve them.
• How building finishes and plant components affect
  facility cleanliness.
• Pharmaceutical Equipment

4
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.

5
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.
6
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)
7
Air Pressure Cascade
8
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.

9
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. ?

10
Typical OSD Plant Cross-contamination
Protection
What should the room pressures be ?
11
Dispensary Layout
Is this a good layout ?
PIC/S PH 1/97 (Rev.3) 3.3 3.12
12
Improved Dispensary Layout
Airflow direction
What should the room pressures be ?
13
Sampling Booth Layout (1)
EXTRACT HOOD
SAMPLING BOOTH
WAREHOUSE
14
Poor Design Extract System
Section Through Sampling Booth
15
Sampling Booth Layout (2)
UDAF HOOD
SAMPLING BOOTH
AIR LOCK
AIR LOCK
CHANGE
Step-over-bench
16
Typical Section Through Sampling Boooth
17
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 (lt 25C)

18
Ablution Layout 1
Production Plant
Toilets
Staff
Change Room
Staff
19
Ablution Layout 2
Production Plant
Change Room
Toilets
Staff
Staff
20
Change Room Layout
21
Protective Garments Outside ??
It is pointless having a change room if it is not
used properly
22
Sterile Suite Pressure Cascade
23
Product Flow Diagram
Wood free zone
RAW MAT. RECEIPT
PACK. MAT. RECEIPT
DISPENSARY
PACK. MAT STORE
MANUFACTURING
PRIMARY PACK MAT. CLEAN DOWN
PRIMARY PACKING
GMP ZONE
SECONDARY PACKING
DISPATCH
24
Staff flow Diagram
STAFF ENTRY
CANTEEN
RAW MAT. RECEIPT
PACK. MAT. RECEIPT
DISPENSARY
CHANGE
PACK. MAT STORE
GMP CHANGE
PRODUCTION
PRIMARY PACK MAT. CLEAN DOWN
PRIMARY PACKING
GMP ZONE
SECONDARY PACKING
DISPATCH
25
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.

26
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.

27
Case Study Penicillin Plant
MALE ABLUT.
Add room pressures, Cleanroom class and comment
on layout
LAUNDRY
FINISH. GOODS
28
Case Study Penicillin Plant
29
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.

30
Building Finishes
31
Floors / drains
Tiled Floor
Epoxy Floor
32
Poor Good Windows
Bacteria City !!!
33
Paint Finish

• Not only building paintwork must be considered
  but also equipment

Is there anything wrong with this Tablet Press?
34
Building Equipment Finishes
35
Services Distribution
Impossible to clean!
Easy to clean!
36
Keep a Balance

• Dont ignore building finishes

and then go overboard on staff dress code.
37
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)

38
Split Unit
Poor quality Air filter
Cooling Coil
Condensate drip tray
Fan liberates dust into the air
39
Fluid Bed Drier

• Is the quality of the
• supply air to the FBD
• correct?
• What filtration is used?
• Is the exhaust air filtered?

40
Group session
Airlock
41
Modified Layout with Cascade
MAL Material Air Lock PAL Personnel Air Lock
42
Product Flow Diagram
Work session Connect the arrows between
processes for Product Flow and Staff Flow
Raw Mat. Store
Quarantine
Released Materials
Primary Change room
Sampling A/L
Sampling A/L
GMP Change Room
Pack Mat. Store
Sampling Booth
Dispensary Pre-Staging
Dispensary Post-Staging
Dispensary Weiigh Booth
Primary Pack Mat. Clean Down
Secondary Packing
Pharmaceutical Manufacturing
Primary Packing
F/G Dispatch
43
Product Flow Diagram
Work session Connect the arrows between
processes for Product Flow and Staff Flow
Raw Mat. Store
Quarantine
Released Materials
Primary Change room
Sampling A/L
Sampling A/L
GMP Change Room
Pack Mat. Store
Sampling Booth
Dispensary Pre-Staging
Dispensary Post-Staging
Dispensary Weiigh Booth
Primary Pack Mat. Clean Down
Secondary Packing
Pharmaceutical Manufacturing
Primary Packing
F/G Dispatch