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Module 13 | Slide 1 of 30 January 2006

Good Practices in

Production and QualityControl

Basic Principles of GMP

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 andproducts, production, quality control, release, storage anddistribution 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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Walls, floors, ceilings smooth and easy to clean

No ledges or areas wheredust can accumulate

Prevention of build-up of dirtand dust to avoidunnecessary risks of

contamination

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16.10 - 11

Good Practices

Avoidance of Cross-Contamination I

Special precautions should be taken to prevent generation anddissemination of dust

Proper air control supply and extraction, suitable quality

Due to uncontrolled release of:

dust, gas, particles, vapours, sprays, organisms, residue, insects

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16.12(a)

Good Practices

Avoidance of Cross-Contamination II

Dedicated and self-contained areas for:

Live vaccines

Live bacterial preparations Certain other biological materials

Penicillin products

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16.12(b)

Good Practices

Avoidance of Cross-Contamination III

Campaign production:

Separation in time

Followed by appropriate cleaning Validated cleaning procedure

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16.12 (c and d)

Good Practices

Avoidance of Cross-Contamination IV

Ventilation systems and airlocks

Appropriately designed ventilation system with air supply andextraction systems

Supply or incoming air should be filtered

Recirculation of air versus 100% fresh air supply

Proper airflow patterns

Pressure differentials

Appropriately designed airlocks

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16.12(e)

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 differentproducts

Garments need to be cleaned

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16.12(f, h and i)

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

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16.12(g)

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)

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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, maintenancepersonnel, cleaners

the more critical the area - fewer number of persons there

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Good Practices


Sanitation

II

Simultaneous operations

not permissible to process different products in different areaswith a common ventilation system

permissible to carry out secondary packaging activities fordifferent products within a packing hall with adequate physicalseparation

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Good Practices


Sanitation

III

Area clearance checks

Process of checking

all materials and documentation from the previous batchremoved

all plant and equipment thoroughly cleaned and appropriate

status labelling

checklist useful

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Good Practices


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 tobe 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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Line opening:

Includes checks onmaterials 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 ofsame 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 expirydated

Final rinse with purified water, or water for injection (for sterile products)

Full records kept

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Good Practices


Sanitation

VI

Water systems

Water - major constituent of most products

SOP for cleaning and sanitization of the water purification systemshould 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 downand disinfection before manufacturing recommences

Area clearance by QC

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17.3

Good Practices

Good Practices in Quality Control (QC)

Complete module on Quality Control Laboratories. This section onlyreflects 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 experiencedperson with one or several control laboratories at his or her disposal

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17.3(a)

Good Practices

Basic Requirements for Quality Control

Resources

Adequate facilities

Trained personnel

Approved procedures

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17.3(a)

Good Practices


Tasks

Sampling

Inspecting

Testing

Monitoring

Releasing/rejecting

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17.3(a)

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 b- e

Good Practices


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 qualityand comply with marketing authorization, are in correct containers andhave correct labels

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17.3 f- h

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

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17.4

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

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17.5

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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17.6

Good Practices

QC Access

QC Personnel must have access to production areas:

for sampling

and investigation

As appropriate

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Part One 3.1, 3.2

Good 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

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