Basic Principles of GMP

Good Practices in
Production and
Quality Control
Section 16 and 17

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Good Practices
Objectives
Discuss aspects of good practices in production
Discuss aspects of good practices in quality control
Group session

Module 13

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January 2006

Good Practices
Manufacture
WHO Definition: All operations of purchase of materials and
products, production, quality control, release, storage and
distribution of pharmaceutical products, and the related controls
Production and QC are parts of GMP
Separate training module on QC

Glossary

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Good Practices
Design of Premises
Design
Walls, floors, ceilings, ledges, drains, air supply, dust extraction
Prevention of build-up of dirt and dust to avoid unnecessary risks of
contamination
Cleaning programme, appropriate cleaning, cleaning records
Effective cleaning and disinfection
choice of materials and chemicals, validation
Drains prevent backflow

12.2, 12.3, 12.7, 12.9, 12.29

Protection from insects, birds, vermin and weather

from receipt of raw materials to dispatch of released product

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Basic Principles of GMP

Walls, floors, ceilings

smooth and easy to clean
No ledges or areas where
dust can accumulate
Prevention of build-up of dirt
and dust to avoid
unnecessary risks of
contamination

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Good Practices
Avoidance of Cross-Contamination I
Special precautions should be taken to prevent generation and
dissemination of dust
Proper air control supply and extraction, suitable quality
Due to uncontrolled release of:
dust, gas, particles, vapours, sprays, organisms, residue, insects

16.10 - 11

Module 13

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Good Practices
Avoidance of Cross-Contamination II

Dedicated and self-contained areas for:

Live vaccines
Live bacterial preparations
Certain other biological materials
Penicillin products

16.12(a)

Module 13

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Good Practices
Avoidance of Cross-Contamination III
Campaign production:
Separation in time
Followed by appropriate cleaning
Validated cleaning procedure

16.12(b)

Module 13

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Good Practices
Avoidance of Cross-Contamination IV
Ventilation systems and airlocks
Appropriately designed ventilation system with air supply and
extraction systems
Supply or incoming air should be filtered
Recirculation of air versus 100% fresh air supply
Proper airflow patterns
Pressure differentials
Appropriately designed airlocks
16.12 (c and d)

Module 13

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Good Practices
Avoidance of Cross-Contamination V
Clothing
Protection of operator and product
Highly potent products or those of particular risk - need for
special protective clothing
Personnel should not move between areas producing different
products
Garments need to be cleaned
16.12(e)

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Good Practices
Avoidance of Cross-Contamination VI
Cleaning and decontamination
Procedure for removing soil and dirt
Remove all cleaning chemical residues or disinfectant residues
Remove and/or reduce micro-organisms
Validated (known effectiveness of the procedure)
Use cleanliness status labels
Test for residues
16.12(f, h and i)

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Good Practices
Avoidance of Cross-Contamination -VII
Closed processing systems
For example: totally enclosed water purification systems
Tanks fitted with appropriate filtration - without removable lids
Present special cleaning difficulties, sometimes use
clean-in-place (CIP)

16.12(g)

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Good Practices
Production Operations Sanitation I
Work-flow
designed to avoid potential contamination
Access
to production areas restricted to authorized personnel
direct operators, QC staff, warehouse staff, maintenance
personnel, cleaners
the more critical the area - fewer number of persons there

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Good Practices
Production Operations Sanitation II

Simultaneous operations
not permissible to process different products in different areas
with a common ventilation system
permissible to carry out secondary packaging activities for
different products within a packing hall with adequate physical
separation

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Good Practices
Production Operations Sanitation III

Area clearance checks

Process of checking
all materials and documentation from the previous batch
removed
all plant and equipment thoroughly cleaned and appropriate
status labelling
checklist useful

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Good Practices
Production Operations Sanitation IV
Area clearance checks
The area clearance check should be carried out by two people
between batches of same product, acceptable for both checks to
be carried out by production personnel
for product changeover, second check carried out by QC staff
all checks carried out in accordance with written SOP and results
recorded on the batch documentation.

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Basic Principles of GMP

Line opening:
Includes checks on
materials and components
Batch number
Expiry date
Printed packaging material
including cartons, leaflets,
foil . . .

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Good Practices
Production Operations Sanitation V
Cleaning and cleaning validation
degree of cleaning depends on whether consecutive batches are of
same or different product
Check cleaning agent is fully removed
If possible hot water alone used for cleaning
all cleaning and disinfecting solutions carefully prepared and expiry
dated
Final rinse with purified water, or water for injection (for sterile products)
Full records kept

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Good Practices
Production Operations Sanitation VI
Water systems
Water - major constituent of most products
SOP for cleaning and sanitization of the water purification system
should include distribution pipework
Validation and removal of disinfectant before reuse

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Good Practices
Production Operations Sanitation VII
Maintenance and repair
activities inevitable in manufacturing area
Should present no risk to product
Whenever possible, all planned maintenance outside normal
operating hours
Emergency work in working area followed by thorough clean down
and disinfection before manufacturing recommences
Area clearance by QC

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Good Practices
Good Practices in Quality Control (QC)
Complete module on Quality Control Laboratories. This section only
reflects some aspects of good practices in QC labs
Each manufacturer should have a QC Department
Independence from production and other departments is fundamental
Under the authority of an appropriately qualified and experienced
person with one or several control laboratories at his or her disposal
17.3

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Good Practices
Basic Requirements for Quality Control
Resources
Adequate facilities
Trained personnel
Approved procedures

17.3(a)

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Good Practices
Basic Requirements for Quality Control
Tasks
Sampling
Inspecting
Testing
Monitoring
Releasing/rejecting
17.3(a)

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Good Practices
Basic Requirements for Quality Control - I
Objects
Starting materials
Packaging materials
Intermediates
Bulk products
Finished products
Environmental conditions
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17.3(a)

Good Practices
Basic Requirements for Quality Control II
1. Sampling: Methods and personnel approved by QC department
2. Qualification and validation done
3. Making records
4. Ensure ingredients and finished products are of the required quality
and comply with marketing authorization, are in correct containers and
have correct labels
17.3 b- e

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Good Practices
Basic Requirements for Quality Control III
5. Records of tests made
6. Review production documentation
7. Assess deviations
8. Retain samples of starting materials and products
9. Release of batches together with the authorized person
17.3 f- h

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Good Practices
Other Duties of the Quality Control Department
1. Establish, validate and implement QC procedures
2. Evaluate, store and maintain reference standards
3. Correct labelling of containers and materials and products
4. Monitor stability of APIs and products
5. Participate in complaint investigations
6. Participate in environmental monitoring
17.4

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Good Practices
Assessment of Finished Products
Should embrace all relevant factors, including:
production conditions
in-process test results
manufacturing documentation
compliance with finished product specification
examination of the finished pack

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17.5

Good Practices
QC Access
QC Personnel must have access to production areas:
for sampling
and investigation
As appropriate

17.6

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Good Practices
Quality Control - summary
QC is part of GMP - refer to the handout
sampling
authorization
specifications
definition of product quality
testing
laboratory operations
release procedures
release decisions
recalls and complaints
investigation and reporting
decision-making in all
quality matters
Part One 3.1, 3.2

Module 13

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