Good Manufacturing

Practices
Good Manufacturing Practices

Presentation on GMP (Production
focus)
Product specific focus
Group session

Presentation on GMP (QC focus)
Product specific focus
Group session
GMP: World Health Organization

WHO Technical Report Series, No. 908,
2003, Annex 4. Good Manufacturing
Practices for pharmaceutical products:
main principles

WHO Technical Report Series, No. Annex
3. Water

WHO Technical Report Series, No. Annex
3. HVAC

Introduction
General considerations
Glossary

Quality management in the drug industry: philosophy and
essential
elements

1. Quality assurance
2. Good manufacturing practices for pharmaceutical products
(GMP)
3. Sanitation and hygiene
4. Qualification and validation
5. Complaints
6. Product recalls
7. Contract production and analysis
General
The contract giver
The contract accepter
The contract
8. Self-inspection and quality audits
Items for self-inspection
Self-inspection team
Frequency of self-inspection
Self-inspection report
Follow-up action
Quality audit
Suppliers audits and approval
9. Personnel
General
Key personnel
10. Training
11. Personal hygiene
12. Premises
General
Ancillary areas
Storage areas
Weighing areas
Production areas
Quality control areas
13. Equipment
14. Materials
General
Starting materials
Packaging materials
Intermediate and bulk products
Finished products
Rejected, recovered, reprocessed and reworked
materials
Recalled products
Returned goods
Reagents and culture media
Reference standards
Waste materials
Miscellaneous
15. Documentation
General
Documents required


16. Good practices in production
General
Prevention of cross-contamination and
bacterial contamination during production
Processing operations
Packaging operations

17. Good practices in quality control
Control of starting materials and intermediate,
bulk and finished products
Test requirements
Batch record review
Stability studies
Production
Utilities
Equipment
Dosage form and data
verification (development,
validation, biobatch, stability,
BMR and specification)
Quality control
API, excipients
Packaging material
Data verification (e.g. stability)
Production
Product focus
Premises
Utilities
Equipment
Dosage form and data
verification (development,
validation, biobatch, stability,
BMR and specification)
Documentation
Where to start the inspection?
Facility layout
Flow of personnel and
material, activities
Product list
Type of products, dosage
forms, activities
Utilities (HVAC, water, etc)
Validation status

Q C


Offices
Gowning

Canteen
Incoming
goods

Corridor



Corridor

Shipping
Corridor




Packaging
Weighing Processing


Filling

Raw
Materials
&
Packaging
Storage


Washing

Machine
Shop



Finished
Products
Storage

Corridor
Utilities and Services Waste Treatment






Zone: Clean

Zone: Packaging

Zone: Controlled
Example of Materials and People Flow
Sampling (starting materials and
packaging materials)
Weighing
Mixing
Milling
Sieving/sifting/screening
Granulation
Drying
Sieving
Blending
Compression
In process bulk stores
Packaging areas (primary and
secondary packaging)
Finished product
Multi-product
Various tablets
Uncoated artesunate

Risk of cross-contamination and
contamination
Non dedicated areas and
equipment
Batch to batch consistency
Batch Manufacturing Document
Formula and manufacturing steps
API and excipients
Properties and requirements for
temperature or RH control
Material quantities, batch size
Sub lots
Equipment and utilities
Production areas
Sieving/sifting sifter (e.g. vibrosifter)
Mixing mixer
Granulation - granulator
Drying fluid bed drier
Blending octagonal blender
Compression compression machine
Packaging - blister machine

Others include Metal detector, sieves,
punches and dies

In process quality control instruments and
equipment may include hardness tester,
disintegration tester, balance, caliper
HVAC air supply and extraction
Compressed air machine
operation, drying of equipment and
parts
Water washing, rinsing,
manufacture
Steam cleaning
The environment may be influenced by:

Light
Temperature
Humidity
Air movement
Microbial contamination
Particulate contamination

Uncontrolled environments can lead to:
Product degradation
Product contamination
Loss of Product & Profit
HVAC: GMP and GEP
Effective ventilation
Cross-contamination and
contamination
Qualification/validation
Design
Installation
Operation
Performance

Q C


Offices
Gowning

Canteen
Incoming
goods

Corridor



Corridor

Shipping
Corridor




Packaging
Weighing Processing


Filling

Raw
Materials
&
Packaging
Storage


Washing

Machine
Shop



Finished
Products
Storage

Corridor
Utilities and Services Waste Treatment






Red: Supply

Green: Exhaust

Air supply and extraction
Filters

Fan

Flow rate controller

Control damper

Humidifier

Cooling coil


Ducts


Incorrect retention rate/leaking/badly
installed
Low air flow loss of pressure cascade

Blocked poor pressure cascade cross-
contamination
Poorly adjusted, bad pressure differential
system
Bad water/steam quality/poor drainage/

No elimination of condensed water/poor
drainage/stagnating water

Inappropriate material/internal insulation
Leaking ducts
Type of water
Intended use
Quality (specification)
Design of the system
Qualification and validation
Ongoing monitoring and quality
control
Sampling, testing, trends
Validation Master Plan

Manufacturing areas
Utilities
Equipment
Manufacturing process
Cleaning validation
Computer systems
Others
From receiving to stores
Sampling and weighing
Manufacturing areas
Utilities
Documentation review
Powder
Container
Floor Scale
Temperature Cooling coil
Relative humidity Dehumidifier
Particulate matter Filters
Air movement and
pressure differentials
Fan
ISPE Baseline Vol. 2 #6.3.3 (d)
WHO HVAC Guideline
Production
Room
F
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C
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D
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F
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C
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I
N
G

C
O
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P
R
I
M
A
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Y
F
I
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T
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R
S
U
P
P
L
Y
A
I
R

F
A
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AIRHANDLING UNIT
R
S
HEPA filters
installed?

Cationic column Anionic column
Hygienic pump
Outlets or storage.
Ozone generator
UV light
HCl NaOH
Eluates to
neutralization
plant
Air break to sewer
Drain line
from water softener
Water
must be
kept
circulating
Typical de-ionizer schematic
1
2
3
4
5
6
1
2
3
4
5
6
Return to de-ioniser
Cartridge
filter 5 m
Cartridge
filter 1 m
HVAC
DQ, IQ, OQ, PQ
Important aspects including air
flow direction, filtration, air
changes, pressure differentials

Water
DQ, IQ, OQ, PQ
Sampling and testing
Equipment and utilities
SOPs (operation, cleaning,
calibration)
Records and use logs
Calibration records/certificates
Preventative maintenance and
maintenance
Qualification
Product related
Batch Manufacturing document as
per product dossier
Process Validation protocol and
report
Bio-batch records
Stability batches
Batch records
Other documents
SOPs including:
Cleaning
Complaints
Recalls
Validation protocols and reports
including:
Cleaning validation
Computer validation
Inspection of the quality control
laboratory