Transcript Slide 1
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
GMP applies to production and QC
Separate training module on QC
Glossary
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Good Practices
All activities in accordance with written SOPs
Records made at the time of action – and maintained
Deviations avoided – when occur, follow SOP
– Quality unit involved
Checks on yields - reconciliation
One product at a time in an area
16.2 – 16.5
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Good Practices
All containers, equipment and areas labelled
Access to areas controlled
No non-medicinal products in the areas
In process controls performed
Prevention of mix-ups, contamination and crosscontamination kept in mind
16.6 – 16.9
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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
12.2, 12.3, 12.7, 12.9, 12.29
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 to prevent generation and dissemination of dust
Proper air control – supply and extraction, suitable quality
Risk assessment
Avoid contamination by :
dust, gas,
particles, clothing, skin,
vapours, sprays,
organisms, residue,
insects
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16.10 - 11
Good Practices
Avoidance of Cross-Contamination II
Technical or organizational measures taken
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 (See HVAC module)
Supply or incoming air should be filtered
Filtered recirculation of air or 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
Environmental monitoring (particles and micro)
Effectiveness of systems checked
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16.12(f, h and i), 16.13,
16.14
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
Processing operations
Always ensure the work area is ready for the process
(e.g. line opening)
Environmental and in-process controls done and
recorded
Deviations and failures recorded
Cleaning performed within specified (validated) time
limits
16.15 – 16.20
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Good Practices
Processing operations
Use clean containers
All pipes, equipment, instruments are:
– suitable for use, integrity checks
– calibrated and verified / checked
– in good state of repair
– correct connections
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16.21 – 16.24
Good Practices
Packaging operations
No risk of mix-ups, contamination and cross-contamination
Preferrably physical separation between lines
Area indicates product under process
Filling followed by sealing and labelling- no delays
Correct performance e.g. overprinting, labels, leaflets
– Automated checks preferred
16.25 – 16.30
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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
Packaging operations
Online control during packaging should include at least checks on:
– general appearance of the packages;
– whether the packages are complete;
– whether the correct products and packaging materials are
used;
– whether any overprinting is correct;
– the correct functioning of line monitors.
Samples taken away from the packaging line should not be
returned.
16.32
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Good Practices
Packaging operations
Reintroduction - only after special inspection, investigation and
approval. Detailed records of this operation.
Discrepancy in reconciliation investigated and recorded before
release.
Unused batch-coded packaging materials destroyed.
Returning of unused materials to stores – SOP followed
Batch records reviewed as part of batch release
Investigation in case of discrepancies
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16.33 – 16.36
Good Practices
Production Operations – Sanitation – I
Work-flow
designed to avoid potential contamination , mix-ups and errors
Access
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 – 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
QC concerned with sampling, testing, specifications
QC should be independent from production
17.1. – 17.2.
Involved in various areas – not confined only to the laboratory
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Good Practices
Each manufacturer should have a QC “function”
Supervised by a person with qualification and experience
Resources should include:
Adequate facilities
Trained personnel
Approved procedures for all activities
Specifications and test procedures
Pharmacopoeia
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17.3(a)
Good Practices
Basic Requirements for Quality Control – II
1. Sampling inspecting and testing of materials, bulk, finished
products
2. Monitoring environmental conditions
3. Qualification and validation
4. Maintaining records of actions, deviations, investigations
5. Ensure ingredients and finished products are of the required
quality and comply with marketing authorization
6. Keeping retention samples
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17.3 .
Good Practices
Other responsibilities include
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
7. Participate in Quality Risk Management programs
17.4
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Good Practices
QC Access
QC personnel must have access to production
and other areas
Sampling e.g. water system, steam,
environmental monitoring
For investigations
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17.5
Good Practices
Sampling
Avoid contamination, cross-contamination and
mix-ups during sampling - no adverse effects
Sampled containers labelled and re-sealed
Clean sampling equipment used - stored
separately from other laboratory equipment
17.8 – 17.10
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Good Practices
Control of starting materials and intermediate, bulk and
finished products – and printed packaging material
Each lot/batch examined following receipt
Samples taken - representative of the batch
Samples tested according to test procedures
Results checked by supervisor prior to release or
17.6 – 17.7, 17.15
rejection
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Good Practices
Each sample container should bear a label indicating:
(a) the name of the sampled material;
(b) the batch or lot number;
(c) the number of the container from which the sample was taken;
(d) the number of the sample;
(e) the signature of the person who has taken the sample;
(f) the date of sampling.
17.11
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Good Practices
Out of specification results
SOP for OOS investigation followed
OOS reported without delay
Investigated
Action taken – see also guidelines from stringent regulatory
authorities)
17.12
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Good Practices
Test requirements: Starting and packaging materials
Materials tested prior to release
Results checked by QC manager (meet specification)
An identity test on a sample from each container normally
required
Reduced sampling and testing subject to certain
17.13-17.14
conditions in supplier qualification
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Good Practices
Reduced sampling: A validated procedure
Consider the nature and status of the manufacturer and supplier
(GMP);
QA system of the manufacturer of the starting material;
Manufacturing conditions;
17.14
nature of the starting material and products in which it will be used
– coming from a single product manufacturer or plant;
– coming directly from a manufacturer, or in the manufacturer’s sealed container where
there is a history of reliability, and regular audits of the manufacturer’s QA system
are conducted by the purchaser (the manufacturer of the medicinal product) or by an
officially accredited body.
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Good Practices
Not applicable normally to:
starting materials supplied through agents and
brokers where the source of manufacture is
unknown or not audited;
starting materials for use in parenteral products
17.14
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Good Practices
Can results be taken from the Certificate of Analysis (from the
supplier?)
Subject to appropriate periodic validation
Reliability of the supplier’s analysis
On-site audits of the supplier’s capabilities
Original COAs (not photocopies) or authenticity assured
COAs must contain relevant information such as name and address
of supplier; signatures, qualifications, materials, batch number,
specifications, results, dates
17.16
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Good Practices
In-process control records – keep as part of the
batch records
Each batch of finished product – confirm
compliance with specification before release
If a product does not meet the specification –
rejected
17.17 – 17.19
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Good Practices
Review of Records
QC records reviewed as part of batch approval process
Batch failure should be thoroughly investigated - written record of
the investigation – extend to other batches if needed
Retention samples kept of finished product
– in their final packaging
– stored under the recommended conditions
– Samples of active starting materials and excipients also kept
17.20- 17.21
Sufficient quantity to permit at least two full re-examinations.
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Good Practices
Stability studies
QC to evaluate the quality and stability of finished pharmaceutical
products and, when necessary, of starting materials and
intermediate products
Establish expiry dates and shelf-life specifications on the basis of
stability tests related to storage conditions
Stability determined prior to marketing
Significant changes in processes, equipment, packaging
materials,
17.2217.23,
17.25
etc. – stability testing.
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Good Practices
Written programme for ongoing stability consisting of:
(a) complete description of the medicine involved in the study;
(b) testing parameters and methods;
(c) provision for the inclusion of a sufficient number of batches;
(d) the testing schedule for each medicine;
(e) provision for special storage conditions;
(f) provision for adequate sample retention
17.24
(g) data summary, evaluation and the conclusions of the study.
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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
2.1, 17.1 - 17.3
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