QUALITY MANAGEMENT

GMP FOR PHARMACEUTICAL PRODUCT (CPOB)

Modul-6
CRITICAL SUPPORTING FACILITIES
Wayan Redja
FACULTY OF PHARMACY INSTITUTE OF SCIENCE AND TECHNOLOGY
JAKARTA

2021
 Utilities

AHU (Air Handling Unit) or HVAC (Heating

Ventilation and Air-Conditioning) Systems
Sistem Pengendali Udara

Water Treatment for Pharmaceutical Use

Sistem Pengolahan Air untuk Farmasi

Compressed Air/Gas
Sistem Udara Tekan
WR01
 AHU/ HVAC
Definition
AHU (Air Handling Unit) is air controlling system to meet the quality
parameter of air (i.e. temperature, RH , particles, microbes, air change)
as required by GMP for a particular room classes to protect the quality
of materials or products from cross-contamination and degradatioan.

Types of AHU
> Circulated Air Sytem
> Full Fresh Air System
> Exhaust Air System

Purpose
To protect the quality of product from cross-contamination, degradation,
and to provide comfortable and safe environment for people
WR03
WR08
 Production Room Classification and Requirements
Temp RH Qty of particles / m3
Room Classes o
C ≥0,5μm ≥5μm
% AC/
Qty of
hr
Microbe/

m3

•
A <1 >120
1 100 B 3.5x103 0 5 40-60
WA
2 10.000 C 16-25 45-55 3.5x105 2x103 100 20-40
D
GA 3 100.000 E 20-28 30-40
E 20-28 45-75 3.5x106 2x104 500 5-20
F
WA=White Area (Sterile), GA=Grey Area (Non-sterile), BA=Black Area (Uncontrolled Air)
BA 4 # Pressure difference between different room classes = 10 to 15 Pa WR16
G
 Introduction to AHU/HVAC

How to provide suitable AHU/HVAC?

It depends on a number of criteria:
Clean area classification or level of protection
Type of product
Occupancy
Climatic condition and locations.
Location of air terminals and directional air flow
Configuration of the room, air supply, and extract
locations

WR04
 Clean Area

Clean Area (Clean Room)

An area (or room) with defined environmental control of
particulate and microbial contamination, constructed and
used in such a way to reduce the introduction, generation
and retention of contaminants within the area.

Purpose
To facilitate production processes in which pharmaceutical
starting materials and products, utensils and equipment are
exposed within the area.

WR05
 BAGAN AHU
BPOM, Juknis SPK 01/CPOB/2013

WR07
 Full Fresh-Air System AHU

-CC
6 1 5 4a 2 3

1 Primary filter, 30% 5 Cooling coil

2 Secondary filter, 90% 6 Damper PRODUCTION
3 HEPA filter, 99,95% F Fresh air FACILITY
4a Supply air fan E Exhaust air handling
4b Exhaust air fan unit (optional filtration)

6 4b 3 2 1

Exhaust-air handling unit WR09

 Recirculation System AHU
* Chemical Drier 4
Desiccant Wheel Reactivation 1

RHC
Air Fan
E Reactivation Air F

+
Returned Air

Process Air
Fan

5 2 3
Supply

CC
Air Fan
F
● ●
S

1 1 Primary Air Filter

-
2 Secondary Air Filter Supply Air Handling Unit
3 HEPA Filter
4 Re-heat Coil Low RH
5 Cooling Coil Production Suite
F Fresh Air
E Exhaust Air
S Supply Air
Leakage
Returned Air
WR10
WR11
 AHU KELAS E
BPOM, Juknis SPK 01/CPOB/2013

WR12
AHU KELAS C
BPOM, Juknis SPK 01/CPOB/2013

WR13
AHU KELAS A DAN B
BPOM, Juknis SPK 01/CPOB/2013

WR14
WR15
WATER TREATMENT SYSTEM FOR
PHARMACEUTICAL USE
SPA
WATER TREATMENT FOR PHARMACEUTICAL USE
SYSTEM PENGOLAHAN AIR UNTUK FARMASI (SPA)

Definition
Water purification system is water processing installation to purify
the feed water to produce pure water that meet the spesification for
•
preparation of pharmaceutical products.

Types of Water for Pharmaceutical Use

> Pure Water: demineralized water, distilled water.
> Water for Injection
Occupancy
Outside air conditions

WR06
 WATER TREATMENT SYSTEM
SISTEM PENGOLAHAN AIR (SPA)

• Distillation
• Ion Exchange
• Reverse Osmoses
• Ultrafiltration
• Deionization

WR17
 SISTEM PENGOLAHAN AIR / SPA
(WATER TREATMENT SYSTEM)
WHAT?
Water Treatment System is water purification to produce
Water for Pharmaceutical Use (WPU) that fulfill the
pharmacopoeia specification for a particular pharmaceutical
product.
• Purified Water
Purified drinking water by distillation, ion exchange, reverse osmosis,
or other appropriate process.
• Water for Injection
The highest quality of distilled Purified Water used as an intermediate
or bulk product for injection.
• Highly Purified Water, EP
The highest quality of Purified Water produced by combined methods
of RO, ultrafiltration and deionization
WR18
 SISTEM PENGOLAHAN AIR / SPA
(WATER TREATMENT SYSTEM)

WHY?
 Purified water plays an important and critical role as a
raw material for pharmaceutical products.
 Water is good media for microbe, and can dissolve,
absorb, adsorb, suspend many compounds including
poisonous contaminants.
 As raw material, purified water is directly used without
prior test.
 Microbial test is obtained after the water has been used,
care should be taken for microbiological contamination
and proliferation into the system.
WR19
 BASIC CONCEPTS OF
PURIFIED WATER TREATMENT DESIGNS
How?
Pengo- Penghi Penghi- Pengo- Penyim
Lahan langan Ion langan Ion Polishing lahan panan &
Awal Primer Sekunder Akhir WFI Distri-
busi

RO Continuous Mixed
Feed EDI Bed Ion
Water
RO Ultra-
filtrasi
Penukar Distilasi
Ion Micro-
filtration
Penukar Penukar
Ion Ion UV Lamp

Distilasi
WR20
Feed Water

 Drinking Water
 Natural Water
- Deep well
- River
- Lake
- Sea

WR21
Water Treatment for Drinking Water
(PAM)
 Precipitation
 Coagulation
 Filtration (sand, carbon active)
 Softening
 Disinfection
 Iron removal
 Removal of organik /specific
inorganic compounds
WR22
WFI

WR23
 Qualification of
Water Treatment System

 Design Qualification (DQ)

 Installation Qualification (IQ)
 Operational Qualification (OQ)
 Performance Qualification (PQ)
- Phase-1 (2-4 weeks): Approval of procedures, specification,
demonstration of purified water production and distribution,
chemical and microbiological testing
- Phase-2 (2-4 weeks); Consistent operational parameter,
consistent quality and quantity of product. Water quality fulfill
requirements.
- Phase-3 (12 months): Demonstrate system reliability.
WR24
COMPRESSED AIR/GAS
 COMPRESSED AIR/GAS

 WHAT, WHY, HOW?

 AIR/GAS IMPURITIES
 CONFIGURATION SYSTEM
 MONITORING SYSTEM
 MAINTENANCE AND SAFETY

WR25
 COMPRESSED AIR/GAS
WHAT, WHY, HOW?
WHAT?

One of the Critical Supporting Facilities of Industrial Pharmacy

which will directly affect to the quality of the product if the system
is not function properly, e.g. Compressed Air for Tablet Coating,
Machine Cleaning, Compressed Nitrogen for Ampoule Filling.
 WHY?
Air or gas impurities will directly contact to the product.

 How?
- The system should be design according to the Standard
Guidelines (BPOM, SPK-01/CPOB/2013).
- The system must be properly maintained and monitored.
WR26
 COMPRESSED AIR/GAS

 AIR/GAS IMPURITIES
- Particles
- Water or water vapor
- Oil vapor or oil aerosol
- Microorganism

WR27
 COMPRESSED AIR/GAS

 CONFIGURATION SYSTEM
Compressor
Water separator
Compressed air/gas tank
Prefilter
Oil and high efficiency filter
Desiccant /Heatless absorption dryer
Dust filter
Activated carbon filter
WR28
 COMPRESSED AIR/GAS
 MONITORING SYSTEM
- Pressure and working hours > To avoid leaking
- PDP (Pressure Dew Point)
To understand air drying requirements in preventing the supply of
moisture saturated air to sensitive processes and equipment.

# PDP is the temperature measured at which the water vapor reaches the
maximum saturation in the compressed air within an air compression unit
exceeding the atmospheric air pressure.

PDP depends on the type of dryer used

- Refrigeration dryers, PDP + 30C
- Deliquescent dryers, PDP +100C
- Desiccant dryers, PDP -40 to -700C

WR29
 COMPRESSED AIR/GAS
MAINTENANCE AND SAFETY
SOP FOR:
 Oil stock
 Filter change
 Disposal of oil and water from line water trap
 Leak test along the distribution line
 Monitoring of oil content of the compressed air/gas
 Calibration program for critical sensors

# Care should be taken on safety and the specification of material

used for this critical supporting facility.

WR30
 ASSIGNMENT
1. What are the types of Critical Supporting Facilities for
Pharmaceutical industry and why they are called as such?
2. Why AHU is needed in GMP for Pharmaceutical Product (CPOB)?
3. What is the function of the important parts of AHU System?
4. Compare the diagram of the Full Fresh Air and the Recirculated Air
AHU System. Explain the difference of those two AHU types.
5. Show in a table the requirements of A,B,C,D and E room classes..
6. What errors will occur if the AHU System is not functioning well?
7. Write some methods for water treatment in pharmaceutical industry.
8. Explain with diagram the function of water treatment system by ion
exchange method using deep well water as the feed water.
9. Describe the function and the monitoring system of Compressed
Air/Gas for Pharmaceutical Industry.
10. Explain the method and the reason of the monitoring system of
Compressed Air/Gas for Pharmaceutical Industry
Thank you