Supplementary Training Modules on

Good Manufacturing Practice

Good Practices
for Quality
Control
Laboratories
 Quality Control
Introduction
This Module consists of four parts:

 Part 1: Management and infrastructure

 Part 2: Materials, equipment, instruments and devices

 Part 3: Working procedures, documents and safety

 Part 4: Inspecting the laboratory

Part One.
Supplementary Training Modules on
Good Manufacturing Practice

Good Practices for Quality Control

Laboratories

Part 1: Management and infrastructure

 Quality Control
Objectives

 To discuss Good Practices for Quality Control laboratories

including quality systems and infrastructure

 To understand the role and importance of the Quality

Control laboratory in:
– sampling and testing
– materials, equipment and systems

 To discuss approaches in inspecting a Quality Control

laboratory Part One.
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General
 Many of the recommendations relevant to quality control
testing at the site of the pharmaceutical manufacturer
 In line, and beyond ISO17025
 The QC laboratory provides a service and is like a
manufacturing unit – its “products” include test results,
advice and investigations
 It needs
– buildings, personnel, resources
– equipment, raw materials Part One.
– quality systems
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General
 Activities include sampling, testing
 APIs, excipients, finished products
 Components, packaging materials
 Specifications and test methods
 Planning and organization of work
Part One.
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In Part 1: Management and infrastructure:

 Organization and management

 Quality management systems
 Control of documentation and records
 Data processing equipment
 Personnel
 Premises, equipment, instruments and other devices
Part One.
 Contracts
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Organization and management: (1)

 Function in accordance with national legislation

 Operate in accordance with good practice norms and

standards

 See also general texts on Good Manufacturing

Practices and Good Practices in Quality control
– WHO Technical Report Series, No. 908, 2003,
Annex 4
1.1– 1.2
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Organization and management (2):

 Personnel
– Managerial and technical positions to ensure
operation in accordance with quality systems
– No conflict of interest

 Organizational chart and job descriptions

 Supervision and training

1.3
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Organization and management (3):
The laboratory should have:

 Managerial and technical personnel with authority and resources

 Arrangements to prevent commercial, political, financial and other

pressures or conflicts of interest

 Policy and procedure in place to ensure confidentiality of

— information contained in marketing authorizations,
— transfer of results or reports,
— and to protect data in archives (paper and electronic);
1.3
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Organization and management (4):
The laboratory should:

 Have organizational charts showing e.g. relationships between

management, technical operations, support services and the
quality management system

 Specify personnel responsibility, authority and interrelationships

 Nominate trained substitutes/deputies for personnel

 Provide adequate supervision of staff

1.3
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Organization and management (5):
The laboratory should have:

 Management which has overall responsibility

 A designated quality manager (ensure compliance with the quality

management system). Direct access to top management

 Adequate information flow

 Traceability of the samples (from receipt to test report completion)

 Up-to-date specifications and related documents (paper or

electronic) and safety procedures 1.3
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Organization and management (6):

 A registry should be kept and may include information on

– receiving, distributing and supervising the
consignment of the samples
– keeping records on all incoming samples and
accompanying documents.

 Ensure communication and coordination between the

staff involved in the testing of the same sample in
different units.
1.4. – 1.5.
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Quality Management System (QMS)
 Establish, implement and maintain QMS covering
– Type of activities, range and volume of testing and/or calibration,
validation and verification
– Policies, systems, programmes, procedures and instructions

 Communicated, available, understood and implemented

 Documented in a quality manual

– available to the laboratory personnel
– maintained and updated by a responsible person
2.1
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The quality manual should refer to at least (1):

 Quality policy

 Organizational chart; operational and functional activities

 Operational and functional activities

 Structure of documents

 Internal QM procedures
2.2
 Procedures for tests
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The quality manual should refer to at least (2):
 Qualifications, experience and competencies of personnel

 Initial and in-service training

 Internal and external audit

 Implementing and verifying corrective and preventive actions

 Dealing with complaints

2.2
 Management reviews

 Selecting, establishing and approving analytical procedures

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The quality manual should contain at least (3):

 Handling of OOS results

 Reference substances and reference materials

 Participation in appropriate proficiency testing schemes

and collaborative trials and the evaluation of the
performance

 Selection of service providers and suppliers 2.2

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The quality policy statement should include at
least: intentions and commitment to:
 Standard of service it will provide

 An effective quality management system

 Good professional practice and quality of testing, calibration,

validation and verification

 Compliance with good practices guidelines

 Personnel commitments to quality and the implementation of the

policies and procedures in their work 2.2a
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Authorized, written SOPs should be established,
implemented and maintained. Examples include
procedures on:

 Personnel matters, including qualifications, training, clothing and

hygiene

 Change control; internal audits

 Dealing with complaints

 Corrective and preventive actions

2.3
 Purchase and receipt of materials (e.g. samples, reagents)
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SOPs (2)

 Reference substances and reference materials - procurement,

preparation and control

 Internal labelling, quarantine and storage of materials

 Qualification, calibration and verification of equipment

 Preventive maintenance

 Sampling, and testing of samples, atypical and OOS results

 Validation of analytical procedures 2.3

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SOPs (3)

 Cleaning of laboratory facilities, including bench tops, equipment,

work stations, clean rooms (aseptic suites) and glassware

 Monitoring of environmental conditions, e.g. temperature and

humidity

 Monitoring storage conditions

 Disposal of reagents and solvent samples; and

 Safety measures
2.3
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 Laboratory activities systematically and periodically
audited (internally and, where appropriate, by external
audits or inspections) to verify compliance - CAPA

 Audits by trained and qualified personnel

 Planning and organizing internal audit

 Regular management review (e.g. annually) to cover e.g.

– audit or inspection reports
– investigations (complaints, atypical results) and CAPAs
2.4 - 2.5, 4.4.
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Control of documents

 Documentation is essential part of the QMS

 Procedures to control and review all documents

 Master list maintained

– Current versions and distribution

3.1
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Procedures should ensure that:
 Documents have a unique number, version number and date of
implementation – and are “current”

 Authorized SOPs are available near points of use

 Invalid documents are removed and replaced

 Revised documents refer to the previous document

 Documents are archived, e.g. 5 years and copies are destroyed

3.2 – 3.3.
 Staff are trained for the new and revised SOPs
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Records
 Procedure for the identification, collection, indexing, retrieval,
storage, maintenance and disposal of documents/records

 All original observations, calculations and derived data,

calibration, validation and verification records, etc. and final
results must be retained on record for an appropriate period of
time, e.g.
– whole length of time the drug is on the market

 Records to contain sufficient information to permit repetition of

tests and traceability 4.1 – 4.2
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Records must be:

 Legible, readily retrievable, stored and retained

 In a suitable environment that will prevent modification,

damage or deterioration and/or loss

 Secure, confidential. Access restricted to authorized

personnel.

 Electronic storage and signatures allowed - restricted

access and in conformance with requirements for 4.3

electronic records
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Data processing equipment
Includes computers, automated tests or calibration equipment;
used for collection, processing, recording, reporting, storage or
retrieval of test and/or calibration data

 See recommendations in Appendix 5 to Annex 4 of the Fortieth

report of the WHO Expert Committee on Specifications for
Pharmaceutical Preparations: Supplementary guidelines in good
manufacturing practice: validation. Validation of computerized
systems (12)

 Where used, requires systematic verifications of calculations and

data transfers 5.1
 Quality Control
 Software is documented and appropriately validated or verified

 Procedures are established and implemented for protecting the

integrity of data
– confidentiality of data entry or collection
– storage, transmission and processing
– access control, and audit trail

 Maintenance and an appropriate environment

 Change control

 Back up (intervals, retrievable, storage, no data loss).

5.2
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Personnel
 Sufficient personnel with job descriptions and records proving
appropriate education, training, technical knowledge and
experience

 Ensure the competence of all personnel

 Staff undergoing training should be appropriately supervised and

should be assessed on completion of the training.

 Permanent employees or contract workers

– Contract workers are trained and know the QMS
6.5 – 6.4
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Managerial and technical personnel:

 Head of laboratory (supervisor)

 Technical managers

 Analysts

 Technical staff
6.6
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The Head of laboratory should have
extensive experience in medicine analysis
and laboratory management.
Responsibilities/functions include:
 All key staff have the requisite competence
 Periodic review of adequacy of existing staffing,
management, and training procedures
6.6.a

 Ensuring technical management is supervised

 Quality Control
Technical management to ensure that:
 Procedures are in place and implemented:
– calibration, verification and (re-) qualification of instruments, monitoring of
environmental and storage conditions

 Training programmes are current

 Materials are kept (also poisons and narcotic and psychotropic

substances under the supervision of an authorized person

 Participation in proficiency testing schemes and collaborative trials

where appropriate
6.6 b
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Analysts and technical staff:
 Analysts should be qualified in e.g. pharmacy, analytical chemistry,
microbiology or other relevant subjects, have knowledge, skills and
ability to do the work

 Technical staff should hold diplomas in their subjects awarded by

technical or vocational schools

 Quality manager to ensure compliance with the quality

management system

6.6.c – e
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Premises (1)
 Suitable size, construction and location – appropriate for the
functions and operations

 Instruments and equipment, work benches, work stations and fume

hoods

 Separate rest and refreshment rooms, changing areas and toilets

 Adequate safety equipment and good housekeeping

 Environmental conditions (lighting, energy, temperature, humidity,

air pressure) - monitored, controlled and documented
7.1 – 7.3

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Premises (2)
 Suitable archive facilities - protect and prevent deterioration.
Access controlled

 Highly toxic substances - special precautions such as separate

and dedicated unit or equipment (e.g. isolator, laminar flow work
bench)

 Microbiological testing (see separate WHO guideline)

 In vivo biological testing – separate

 Waste removal including toxic waste

7.4 – 7.8
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Laboratory storage facilities (1)

 Well organized for the correct storage of samples, reagents and
equipment. – locked and access controlled

 Separate areas for samples, retained samples, reagents and

laboratory accessories, reference substances and reference
materials

 Provision for refrigeration (2–8°C) and frozen (-20°C). Controlled,

monitored and recorded. 7.9 – 7.11

 Safety procedures for storage of toxic or flammable reagents

 Quality Control

Laboratory storage facilities (2)

 Poisons, narcotic and psychotropic substances clearly marked

 Kept separately in locked cabinets.

 Designated responsible person to maintain a register

 Gases stored in a dedicated store, if possible isolated from the

main building.

 Gas bottles avoided in the laboratory or safely secured.

7.12 – 7.13
Note: Consider installation of gas generators.
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Equipment, instruments and
other devices
 Laboratory should have necessary
equipment

 Meet requirements and specifications

 Designed, constructed, adapted, located,

calibrated, qualified, verified and
maintained

 Purchased from agents capable of

providing full technical support and 8.1 – 8.3
maintenance when necessary
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Contracts

Purchasing services and supplies

 Procedure for the selection and purchasing of services and
supplies

 Evaluate suppliers of critical consumables, supplies and services

which affect quality of testing - maintain records

 Approved suppliers list

9.1 – 9.3
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Subcontracting of testing
 Subcontracting - in writing and, with approval

 Written contract with duties and responsibilities of each party

 Use organizations approved for the type of activity required

 Periodic assessment of the competence of contracted organization

 No delegation to a third party without prior evaluation and

approval

 Register of all subcontractors 9.3 – 9.8.