Module 13 | Slide 1 of 30 January 2006

Good Practices in Production and Quality Control

Basic Principles of GMP

Section 16 and 17

Module 13 | Slide 2 of 30 January 2006

Good PracticesGood Practices

Objectives

Discuss aspects of good practices in production

Discuss aspects of good practices in quality control

Group session

Module 13 | Slide 3 of 30 January 2006

Good PracticesGood 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

Module 13 | Slide 4 of 30 January 2006

Good PracticesGood 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

Module 13 | Slide 5 of 30 January 2006

Basic Principles of GMPBasic 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 | Slide 6 of 30 January 2006

16.10 - 11

Good PracticesGood 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

Module 13 | Slide 7 of 30 January 2006

16.12(a)

Good PracticesGood Practices

Avoidance of Cross-Contamination II

Dedicated and self-contained areas for: Live vaccines Live bacterial preparations Certain other biological materials Penicillin products

Module 13 | Slide 8 of 30 January 2006

16.12(b)

Good PracticesGood Practices

Avoidance of Cross-Contamination III

Campaign production:

Separation in time

Followed by appropriate cleaning

Validated cleaning procedure

Module 13 | Slide 9 of 30 January 2006

16.12 (c and d)

Good PracticesGood 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

Module 13 | Slide 10 of 30 January 2006

16.12(e)

Good PracticesGood 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

Module 13 | Slide 11 of 30 January 2006

16.12(f, h and i)

Good PracticesGood 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

Module 13 | Slide 12 of 30 January 2006

16.12(g)

Good PracticesGood 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)

Module 13 | Slide 13 of 30 January 2006

Good PracticesGood 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

Module 13 | Slide 14 of 30 January 2006

Good PracticesGood 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

Module 13 | Slide 15 of 30 January 2006

Good PracticesGood 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

Module 13 | Slide 16 of 30 January 2006

Good PracticesGood 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.

Module 13 | Slide 17 of 30 January 2006

Basic Principles of GMPBasic Principles of GMP

Line opening:

Includes checks on materials and components

Batch number

Expiry date

Printed packaging material including cartons, leaflets, foil . . .

Module 13 | Slide 18 of 30 January 2006

Good PracticesGood 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

Module 13 | Slide 19 of 30 January 2006

Good PracticesGood 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

Module 13 | Slide 20 of 30 January 2006

Good PracticesGood 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

Module 13 | Slide 21 of 30 January 2006

17.3

Good PracticesGood 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

Module 13 | Slide 22 of 30 January 2006

17.3(a)

Good PracticesGood Practices

Basic Requirements for Quality Control

Resources

Adequate facilities

Trained personnel

Approved procedures

Module 13 | Slide 23 of 30 January 2006

17.3(a)

Good PracticesGood Practices

Basic Requirements for Quality Control

Tasks

Sampling

Inspecting

Testing

Monitoring

Releasing/rejecting

Module 13 | Slide 24 of 30 January 2006

17.3(a)

Good PracticesGood Practices

Basic Requirements for Quality Control - I

Objects

Starting materials

Packaging materials

Intermediates

Bulk products

Finished products

Environmental conditions

Module 13 | Slide 25 of 30 January 2006

17.3 b- e

Good PracticesGood 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

Module 13 | Slide 26 of 30 January 2006

17.3 f- h

Good PracticesGood 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

Module 13 | Slide 27 of 30 January 2006

17.4

Good PracticesGood 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

Module 13 | Slide 28 of 30 January 2006

17.5

Good PracticesGood 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

Module 13 | Slide 29 of 30 January 2006

17.6

Good PracticesGood Practices

QC Access

QC Personnel must have access to production areas: for sampling and investigation

As appropriate

Module 13 | Slide 30 of 30 January 2006

Part One 3.1, 3.2

Good PracticesGood Practices

Quality Control - summary

QC is part of GMP - refer to the handout sampling specifications testing release procedures recalls and complaints decision-making in all

quality matters

authorization definition of product quality laboratory operations release decisions investigation and reporting