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

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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 Protection from insects, birds, vermin and weather from receipt of raw materials to dispatch of released product
12.2, 12.3, 12.7, 12.9, 12.29

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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

Module 13

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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

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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)

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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)

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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)

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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)

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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
17.5

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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

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