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GOOD LABORATORY PRACTICE REGULATIONS
Table of Provisions (15)
Statutory Text (15 Articles)
GOOD LABORATORY PRACTICE
SUBSIDIARY LEGISLATION 427.56
GOOD LABORATORY PRACTICE
REGULATIONS
30th July, 2004
LEGAL NOTICE 371 of 2004, as amended by Legal Notice 426 of 2012.
The title of these regulations is the Good Laboratory
Practice Regulations.
THE OECD PRINCIPLES OF GOOD LABORATORY PRACTICE (GLP)
Contents
Section I
INTRODUCTION
Preface
1. Scope
2. Definitions of terms
2.1.
Good laboratory practice
2.2.
Terms concerning the organisation of a test facility
2.3.
Terms concerning the non-clinical health and environmental safety
study
2.4.
Terms concerning the test item
Section II
GOOD LABORATORY PRACTICE PRINCIPLES
1. Test facility organisation and personnel
1.1.
Test facility management’s responsibilities
1.2.
Study director’s responsibilities
1.3.
Principal investigator’s responsibilities
1.4.
Study personnel’s responsibilities
2. Quality assurance programme
2.1.
General
2.2.
Responsibilities of the quality assurance personnel
3. Facilities
3.1.
General
3.2.
Test system facilities
3.3.
Facilities for handling test and reference items
3.4.
Archive facilities
3.5.
Waste disposal
4. Apparatus, material, and reagents
5. Test systems
5.1.
Physical/chemical
5.2.
Biological
6. Test and reference items
6.1.
Receipt, handling, sampling and storage
6.2.
Characterisation
(1) Laboratories carrying out tests on chemical products,
in accordance with the Dangerous Substances (Notification)
Regulations, shall comply with the principles of Good Laboratory
Practice as laid down in the First Schedule.
(2) Regulation 2(1) shall apply also where other provisions
provide for the application of the principles of Good Laboratory
Practice in respect of tests on chemical products to evaluate their
safety for man and, or the environment.
(3) These regulations implement the provisions of Directive
2004/9/EC of the European Parliament and of the Council and of
Directive 2004/10/EC of the European Parliament and of the
Council.
Amended by
L.N. 426 of 2012.
The provisions for the inspection and verification of Good Laboratory Practice
which are contained in parts A and B are those contained in Annexes I (Guides for
compliance monitoring procedures for Good Laboratory Practice) and II (Guidance
for the conduct of test facility inspections and study audits) respectively of the
OECD Council Decision-Recommendation on compliance with principles of Good
Laboratory Practice [C(89)87(Final)] of 2 October 1989 as revised by the OECD
Council Decision amending the Annexes to the Council Decision-Recommendation
on compliance with principles of Good Laboratory Practice of 9 March 1995
[C(95)8(Final)].
PART A
REVISED GUIDES FOR COMPLIANCE MONITORING PROCEDURES
FOR GOOD LABORATORY PRACTICE
To facilitate the mutual acceptance of test data generated for submission to
Regulatory Authorities of the OECD member countries, harmonisation of the
procedures adopted to monitor Good Laboratory Practice compliance, as well as
comparability of their quality and rigour, are essential. The aim of this part of the
Annex is to provide detailed practical guidance to the Member States on the
structure, mechanisms and procedures they should adopt when establishing national
Good Laboratory Practice compliance monitoring programmes so that these
programmes may be internationally acceptable.
It is recognised that Member States will adopt Good Laboratory Practice
principles and establish compliance monitoring procedures according to national
legal and administrative practices, and according to priorities they give to, for
example the scope of initial and subsequent coverage concerning categories of
chemicals and types of testing. Since Member States may establish more than one
Good Laboratory Practice Monitoring Authority due to their legal framework for
chemicals control, more than one Good Laboratory Practice compliance programme
may be established. The guidance set forth in the following paragraphs concerns
GOOD LABORATORY PRACTICE
each of these Authorities and compliance programmes, as appropriate.
Definitions of terms
The definitions of terms in the OECD principles of Good Laboratory Practice
adopted in Article 1 of Council Directive 87/18/EEC ( * ) are applicable to this part of
the Annex. In addition, the following definitions apply
-
Good Laboratory Practice principles: principles of Good Laboratory
Practice that are consistent with the OECD principles of Good Laboratory Practice
as adopted in Article 1 of Directive 87/18/EEC,
-
Good Laboratory Practice compliance monitoring: the periodic inspection
of test facilities and, or auditing of studies for the purpose of verifying adherence to
Good Laboratory Practice principles,
-
(National) Good Laboratory Practice compliance programme: the particular
scheme established by a Member State to monitor Good Laboratory Practice
compliance by test facilities within its territories, by means of inspections and study
audits,
-
(National) Good Laboratory Practice Monitoring Authority: a body
established within a Member State with responsibility for monitoring the Good
Laboratory Practice compliance of test facilities within its territories and for
discharging other such functions related to Good Laboratory Practice as may be
nationally determined. It is understood that more than one such body may be
established in a Member State,
-
Test facility inspection: an on-site examination of the test facility’s
procedures and practices to assess the degree of compliance with Good Laboratory
Practice principles. During inspections, the management structures and operational
procedures of the test facility are examined, key technical personnel are interviewed,
and the quality and integrity of data generated by the facility are assessed and
reported,
-
Study audit: a comparison of raw data and associated records with the
interim or final report in order to determine whether the raw data have been
accurately reported, to determine whether testing was carried out in accordance with
the study plan and standard operating procedures, to obtain additional information
not provided in the report, and to establish whether practices were employed in the
development of data that would impair their validity,
-
Inspector: a person who performs the test facility inspections and study
audits on behalf of the (national) Good Laboratory Practice Monitoring Authority,
-
Good Laboratory Practice compliance status: the level of adherence of a
test facility to the Good Laboratory Practice principles as assessed by the (national)
Good Laboratory Practice Monitoring Authority,
-
Regulatory Authority: a national body with legal responsibility for aspects
of the control of chemicals.
Components of Good Laboratory Practice compliance monitoring procedures
Administration
A (national) Good Laboratory Practice compliance programme should be the
responsibility of a properly constituted, legally identifiable body adequately staffed
and working within a defined administrative framework.
*OJ L 15, 17.1.1987, p.29.
GOOD LABORATORY PRACTICE
Member States should
ensure that the (national) Good Laboratory Practice Monitoring
Authority is directly responsible for an adequate ‘team’ of inspectors
having the necessary technical/scientific expertise or is ultimately
responsible for such a team,
publish documents relating to the adoption of Good Laboratory Practice
principles within their territories,
publish documents providing details of the (national) Good Laboratory
Practice compliance programme, including information on the legal or
administrative framework within which the programme operates and
references to published acts, normative documents (e.g., regulations,
codes of practice), inspection manuals, guidance notes, periodicity of
inspections and, or criteria for inspection schedules, etc.,
maintain records of test facilities inspected (and their Good Laboratory
Practice compliance status) and of studies audited for both national and
international purposes.
Confidentiality
(National) Good Laboratory Practice Monitoring Authorities will have access to
commercially valuable information and, on occasion, may even need to remove
commercially sensitive documents from a test facility or refer to them in detail in
their reports.
Member States should
make provision for the maintenance of confidentiality, not only by
Inspectors but also by any other persons who gain access to confidential
information as a result of Good Laboratory Practice compliance
monitoring activities,
ensure that, unless all commercially sensitive and confidential
information has been excised, reports of test facility inspections and
study audits are made available only to Regulatory Authorities and,
where appropriate, to the test facilities inspected or concerned with
study audits and/or to study sponsors.
Personnel and training
(National) Good Laboratory Practice Monitoring Authorities should
ensure that an adequate number of inspectors is available.
The number of inspectors required will depend on
(a) the number of test facilities involved in the (national) Good
Laboratory Practice compliance programme;
(b) the frequency with which the Good Laboratory Practice
compliance status of the test facilities is to be assessed;
(c) the number and complexity of the studies undertaken by those test
facilities;
(d) the number of special inspections or audits requested by
Regulatory Authorities,
ensure that inspectors are adequately qualified and trained.
Inspectors should have qualifications and practical experience in the
range of scientific disciplines relevant to the testing of chemicals.
(National) Good Laboratory Practice Monitoring Authorities should
GOOD LABORATORY PRACTICE
(a) ensure that arrangements are made for the appropriate training of
Good Laboratory Practice inspectors, having regard to their
individual qualifications and experience;
(b) encourage consultations, including joint training activities where
necessary, with the staff of (national) Good Laboratory Practice
Monitoring Authorities in other OECD member countries in order
to promote international harmonisation in the interpretation and
application of Good Laboratory Practice principles, and in the
monitoring of compliance with such principles,
-
ensure that inspectorate personnel, including experts under contract,
have no financial or other interests in the test facilities inspected, the
studies audited or the firms sponsoring such studies,
-
provide inspectors with a suitable means of identification (e.g., a legally
valid identification document).
Inspectors may be
-
on the permanent staff of the (national) Good Laboratory Practice
Monitoring Authority,
-
on the permanent staff of a body separate from the (national)
Good Laboratory Practice Monitoring Authority, or
-
employed on contract, or in another way, by the (national) Good
Laboratory Practice Monitoring Authority to perform test facility
inspections or study audits.
In the latter two cases, the (national) Good Laboratory Practice
Monitoring Authority should have ultimate responsibility for
determining the Good Laboratory Practice compliance status of test
facilities and the quality/acceptability of a study audit, and for taking
any action based on the results of test facility inspections or study audits
which may be necessary.
(National) Good Laboratory Practice compliance programmes
Good Laboratory Practice compliance monitoring is intended to ascertain whether
test facilities have implemented Good Laboratory Practice principles for the conduct
of studies and are capable of assuring that the resulting data are of adequate quality.
As indicated above, Member States should publish the details of their (national)
Good Laboratory Practice compliance programmes.
Such information should, inter alia
-
define the scope and extent of the programme.
A (national) Good Laboratory Practice compliance programme may cover only a
limited range of chem icals, for example, industrial chemicals, pestici des,
pharmaceuticals, etc., or may include all chemicals. The scope of the monitoring for
compliance should be defined, both with respect to the categories of chemicals and
to the types of tests subject to it, for example, physical, chemical, toxicological and/
or ecotoxicological,
-
provide an indication as to the mechanism whereby test facilities enter
the programme.
The application of Good Laboratory Practice principles to health and
environmental safety data generated for regulatory purposes may be mandatory. A
mechanism should be available whereby test facilities may have their compliance
with Good Laboratory Practice principles monitored by the appropriate (national)
Good Laboratory Practice Monitoring Authority,
GOOD LABORATORY PRACTICE
provide information on categories of test facility inspections/study
audits.
A (national) Good Laboratory Practice compliance programme should include
(a) provision for test facility inspections. These inspections include both a
general test facility inspection and a study audit of one or more on-
going or completed studies;
(b) provisions for special test facility inspections/study audits at the request
of a Regulatory Authority, for example, prompted by a query arising
from the submission of data to a Regulatory Authority,
define the powers of inspectors for entry into test facilities and their
access to data held by test facilities (including specimens, SOPs
(standard operating procedures) other documentation, etc.).
While inspectors will not normally wish to enter test facilities against the will of
the facility's management, circumstances may arise where test facility entry and
access to data are essential to protect public health or the environment. The powers
available to the (national) Good Laboratory Practice Monitoring Authority in such
cases should be defined,
describe the test facility inspection and study audit procedures for
verification of Good Laboratory Practice compliance.
The documentation should indicate the procedures which will be used to examine
both the organizational processes and the conditions under which studies are
planned, performed, monitored and recorded.
Guidance for such procedures is available in part B of this Annex,
describe actions that may be taken as follow-up test facility inspections
and study audits.
Follow-up to test facility inspections and study audits
When a test facility inspection or study audit has been completed, the inspector
should prepare a written report of the findings.
Member States should take action where deviations from Good Laboratory
Practice principles are found during or after a test facility inspection or study audit.
The appropriate actions should be described in documents from the (national) Good
Laboratory Practice Monitoring Authority.
If a test facility inspection or study audit reveals only minor deviations from Good
Laboratory Practice principles, the facility should be required to correct such minor
deviations. The inspector may need, at an appropriate time, to return to the facility to
verify that corrections have been introduced.
Where no, or where only minor deviations have been found, the (national) Good
Laboratory Practice Monitoring Authority may
issue a statement that the test facility has been inspected and found to be
operating in compliance with Good Laboratory Practice principles. The
date of the inspections and, if appropriate, the categories of test
inspected in the test facility at that time should be included. Such
statements may be used to provide information to (national) Good
Laboratory Practice Monitoring Authorities in other OECD member
countries, and, or
provide the Regulatory Authority which requested a study audit with a
detailed report of the findings.
GOOD LABORATORY PRACTICE
Where serious deviations are found, the action taken by (national) Good
Laboratory Practice Mon ito rin g A uth ori ties wil l d epend on the particu lar
circumstances of each case and the legal or administrative provisions under which
Good Laboratory Practice compliance monitoring has been established within their
countries. Actions which may be taken include, but are not limited to, the following
-
issuance of a statement, giving details of the inadequacies or faults
found which might affect the validity of studies conducted in the test
facility,
-
issuance of a recommendation to a Regulatory Authority that a study be
rejected,
-
suspension of test facility inspections or study audits of a test facility
and, for example and where administratively possible, removal of the
test facility from the (national) Good Laboratory Practice compliance
programme or from any existing list or register of test facilities subject
to Good Laboratory Practice test facility inspections,
-
requiring that a statement detailing the deviations be attached to
specific study reports,
-
action through the courts, where warranted by circumstances and where
legal/administrative procedures so permit.
Appeals procedures
Problems, or differences of opinion, between inspectors and test facility
management will normally be resolved during the course of a test facility inspection
or study audit. However, it may not always be possible for agreement to be reached.
A procedure should exist whereby a test facility may make representations relating
to the outcome of a test facility inspection or study audit for Good Laboratory
Practice compliance monitoring and/or relating to the action the Good Laboratory
Practice Monitoring Authority proposes to take thereon.
PART B
REVISED GUIDANCE FOR THE CONDUCT OF TEST FACILITY
INSPECTIONS AND STUDY AUDITS
Introduction
The purpose of this part of the Annex is to provide guidance for the conduct of test
facility inspections and study audits which would be mutually acceptable to OECD
member countries. It is principally concerned with test facility inspections, an
activity which occupies much of the time of Good Laboratory Practice inspectors. A
test facility inspection will usually include a study audit or review as a part of the
inspection, but study audits will also have to be conducted from time to time at the
request, for example, of a Regulatory Authority. General guidance for the conduct of
study audits will be found at the end of this Annex.
Test facility inspections are conducted to determine the degree of conformity of
test facilities and studies with Good Laboratory Practice principles and to determine
the integrity of data to assure that resulting data are of adequate quality for
assessment and decision-making by national Regulatory Authorities. They result in
reports which describe the degree of adherence of a test facility to the Good
Laboratory Practice principles. Test facility inspections should be conducted on a
regular, routine basis to establish and maintain records of the Good Laboratory
Practice compliance status of test facilities.
Further clarification of many of the points in this part of the Annex may be
obtained by referring to the OECD consensus documents on Good Laboratory
GOOD LABORATORY PRACTICE
Practice (on, e.g., the role and responsibilities of the study director).
Definitions of terms
The definitions of terms in the OECD principles of Good Laboratory Practice
adopted in Article 1 of Directive 87/18/EEC and in part A of the Annex to this
Directive are applicable to this part of the Annex.
Test facility inspections
Inspections for compliance with Good Laboratory Practice principles may take
place in any test facility generating health or environmental safety data for
regulatory purposes. Inspectors may be required to audit data relating to the
physical, chemical, toxicological or ecotoxicological properties of a substance or
preparation. In some cases, inspectors may need assistance from experts in particular
disciplines.
The wide diversity of facilities (in terms both of physical layout and management
structure), together with the variety of types of studies encountered by inspectors,
means that the inspectors must use their own judgment to assess the degree and
extent of compliance with Good Laboratory Practice principles. Nevertheless,
inspectors should strive for a consistent approach in evaluating whether, in the case
of a particular test facility or study, an adequate level of compliance with each Good
Laboratory Practice principle has been achieved.
In the following sections, guidance is provided on the various aspects of the
testing facility, including its personnel and procedures, which are likely to be
examined by inspectors. In each section, there is a statement of purpose, as well as
an illustrative list of specific items which could be considered during the course of a
test facility inspection. These lists are not meant to be comprehensive and should not
be taken as such.
Inspectors should not concern themselves with the scientific design of the study or
the interpretation of the findings of studies with respect to risks for human health or
the environment. These aspects are the responsibility of those Regulatory
Authorities to which the data are submitted for regulatory purposes.
Test facility inspections and study audits inevitably disturb the normal work in a
facility. Inspectors should therefore carry out their work in a carefully planned way
and, so far as practicable, respect the wishes of the management of the test facility as
to the timing of visits to certain sections of the facility.
Inspectors will, while conducting test facility inspections and study audits, have
access to confidential, commercially valuable information. It is essential that they
e n s u r e t h a t s u c h i n f o r m a t i o n i s s e e n b y a u t h o r i z e d p e r s o n n e l o n l y. T h e i r
responsibilities in this respect will have been established within their (national)
Good Laboratory Practice compliance monitoring programme.
Inspection procedures
Pre-inspection
Purpose
to familiarise the inspector with the facility which is about to be
inspected in respect of management structure, physical layout of
buildings and range of studies.
Prior to conducting a test facility inspection or study audit, inspectors should
familiarise themselves with the facility which is to be visited. Any existing
information on the facility should be reviewed. This may include previous inspection
reports, the layout of the facility, organisation charts, study reports, protocols and
curricula vitae (CVs) of personnel. Such documents would provide information on;
GOOD LABORATORY PRACTICE
the type, size and layout of the facility,
the range of studies likely to be encountered during the inspection,
the management structure of the facility.
Inspectors should note, in particular, any deficiencies from previous test facility
inspections.
Where no previous test facility inspections have been conducted, a pre-inspection
visit can be made to obtain relevant information.
Test facilities may be informed of the date and time of inspector’s arrival, the
objective of their visit and the length of time they expect to be on the premises. This
c o u l d a l l o w t h e t e s t f a c i l i t y t o e n s ur e t h a t t h e a p p r o p r i a t e p e r s o n n e l a n d
documentation are available. In cases where particular documents or records are to
be examined, it may be useful to identify these to the test facility in advance of the
visit so that they will be immediately available during the test facility inspection.
Starting conference
Purpose
to inform the management and staff of the facility of the reason for the
test facility inspection or study audit that is about to take place, and to
identify the facility areas, study(ies) selected for audit, documents and
personnel likely to be involved.
The administrative and practical details of a test facility inspection or study audit
should be discussed with the management of the facility at the start of the visit. At
the starting conference, inspectors should
outline the purpose and scope of the visit,
describe the documentation which will be required for the test facility
inspection, such as lists of on-going and completed studies, study plans,
standard operating procedures, study reports, etc. Access to and, if
necessary, arrangements for the copying of relevant documents should
be agreed on at this time,
clarify or request information as to the management structure
(organisation) and personnel of the facility,
request information as to the conduct of studies not subject to Good
Laboratory Practice principles in the areas of the test facility where
Good Laboratory Practice studies are being conducted,
make an initial determination as to the parts of the facility to be covered
during the test facility inspection,
describe the documents and specimens that will be needed for on-going
or completed study(ies) selected for study audit,
indicate that a closing conference will be held at the completion of the
inspection.
Before proceeding further with a test facility inspection, it is advisable for the
inspector(s) to establish contact with the facility's quality assurance (QA) unit.
As a general rule, when inspecting a facility, inspectors will find it helpful to be
accompanied by a member of the QA unit.
Inspectors may wish to request that a room be set aside for examination of
documents and other activities.
Organisation and personnel
Purpose
to determine whether the test facility has sufficient qualified
GOOD LABORATORY PRACTICE
personnel, staff resources and support services for the variety and
nu m b er of st ud i es un d erta ke n[ t he o rga ni sa ti on al st ru ct u r e is
appropriate, and management has established a policy regarding
training and staff health surveillance appropriate to the studies
undertaken in the facility.
The management should be asked to produce certain documents, such as
floor plans,
facility management and scientific organisation charts,
CVs of personnel involved in the type(s) of studies selected for the
study audit,
list(s) of on-going and completed studies with information on the type
of study, initiation/completion dates, test system, method of application
of test substance and name of study director,
staff health surveillance policies,
staff job descriptions and staff training programmes and records,
an index to the facility’s standard operating procedures (SOPs),
specific SOPs as related to the studies or procedures being inspected or
audited,
list(s) of the study directors and sponsors associated with the study(ies)
being audited.
The inspector should check, in particular
lists of on-going and completed studies to ascertain the level of work
being undertaken by the test facility,
the identity and qualifications of the study director(s), the head of the
quality assurance unit and other personnel,
existence of SOPs for all relevant areas of testing.
Quality assurance programme
Purpose
to determine whether the mechanisms used to assure management that
studies are conducted in accordance with Good Laboratory Practice
principles are adequate.
The head of the quality assurance (QA) unit should be asked to demonstrate the
systems and methods for QA inspection and monitoring of studies, and the system
for recording observations made during QA monitoring.
Inspectors should check
the qualifications of the head of QA, and of all QA staff,
that the QA unit functions independently from the staff involved in the
studies,
how the QA unit schedules and conducts inspections, how it monitors
identified critical phases in a study, and what resources are available for
QA inspections and monitoring activities,
that where studies are of such short duration that monitoring of each
study is impracticable, arrangements exist for monitoring on a sample
basis,
the extent and depth of QA monitoring during the practical phases of the
study,
GOOD LABORATORY PRACTICE
the extent and depth of QA monitoring of routine test facility operation,
the QA procedure for checking the final report to ensure its agreement
with the raw data,
that management receives reports from QA concerning problems likely
to affect the quality or integrity of a study,
the actions taken by QA when deviations are found,
the QA role, if any, if studies or parts of studies are done in contract
laboratories,
the part played, if any, by QA in the review, revision and updating of
SOPs.
Facilities
Purpose
to determine if the test facility, whether indoor or outdoor, is of
suitable size, design and location to meet the demands of the studies
being undertaken.
The inspector should check that
the design enables an adequate degree of separation so that, for
example, test substances, animals, diets, pathological specimens, etc. of
one study cannot be confused with those of another,
environmental control and monitoring procedures exist and function
adequately in critical areas, for example, animal and other biological
test systems rooms, test substance storage areas, laboratory areas,
the general housekeeping is adequate for the various facilities and that
there are, if necessary, pest control procedures.
Care, housing and containment of biological test systems
Purpose
to determine whether the test facility, if engaged in studies using
animals or other biological test systems, has support facilities and
conditions for their care, housing and containment, adequate to prevent
stress and other problems which could affect the test system and hence
the quality of data.
A test facility may be carrying out studies which require a diversity of animal or
plant species as well as microbial or other cellular or sub-cellular systems. The type
of test systems being used will determine the aspects relating to care, housing or
containment that the inspector will monitor. Using his judgment, the inspector will
check, according to the test systems, that
there are facilities adequate for the test systems used and for testing
needs,
there are arrangements to quarantine animals and plants being
introduced into the facility and that these arrangements are working
satisfactorily,
there are arrangements to isolate animals (or other elements of a test
system, if necessary) known to be, or suspected of being, diseased or
carriers of disease,
there is adequate monitoring and record-keeping of health, behaviour or
other aspects, as appropriate to the test system,
the equipment for maintaining the environmental conditions required
for each test system is adequate, well maintained, and effective,
GOOD LABORATORY PRACTICE
animal cages, racks, tanks and other containers, as well as accessory
equipment, are kept sufficiently clean,
analyses to check environmental conditions and support systems are
carried out as required,
facilities exist for removal and disposal of animal waste and refuse from
the test systems and that these are operated so as to minimise vermin
infestation, odours, disease hazards and environmental contamination,
storage areas are provided for animal feed or equivalent materials for all
test systems; that these areas are not used for the storage of other
materials such as test substances, pest control chemicals or
disinfectants, and that they are separate from areas in which animals are
housed or other biological test systems are kept,
stored feed and bedding are protected from deterioration by adverse
environmental conditions, infestation or contamination.
Apparatus, materials, reagents and specimens
Purpose
to determine whether the test facility has suitably located, operational
apparatus in sufficient quantity and of adequate capacity to meet the
requirements of the tests being conducted in the facility and that the
materials, reagents and specimens are properly labelled, used and
stored.
The inspector should check that
apparatus is clean and in good working order,
records have been kept of operation, maintenance, verification,
calibration and validation of measuring equipment and apparatus
(including computerised systems),
materials and chemical reagents are properly labelled and stored at
appropriate temperatures and that expiry dates are not being ignored.
Labels for reagents should indicate their source, identity and
concentration and, or other pertinent information,
specimens are well identified by test system, study, nature and date of
collection,
apparatus and materials used do not alter to any appreciable extent the
test systems.
Test systems
Purpose
to determine whether adequate procedures exist for the handling and
control of the variety of test systems required by the studies
undertaken in the facility, for example, chemical and physical systems,
cellular and microbic systems, plants or animals.
Physical and chemical systems
The inspector should check that
where required by study plans, the stability of test and reference
substances was determined and that the reference substances specified
in test plans were used,
in automated systems, data generated as graphs, recorder traces or
computer print-outs are documented as raw data and archived.
Biological test systems
GOOD LABORATORY PRACTICE
Taking account of the relevant aspects referred to above relating to care, housing
or containment of biological test systems, the inspector should check that
test systems are as specified in study plans,
test systems are adequately and, if necessary and appropriate, uniquely
identified throughout the study, and that records exist regarding receipt
of the test systems and document fully the number of test systems
received, used, replaced or discarded,
housing or containers of test systems are properly identified with all the
necessary information,
there is an adequate separation of studies being conducted on the same
animal species (or the same biological test systems) but with different
substances,
there is an adequate separation of animal species (and other biological
test systems) either in space or in time,
the biological test system environment is as specified in the study plan
or in SOPs for aspects such as temperature, or light/dark cycles,
the recording of the receipt, handling, housing or containment, care and
health evaluation is appropriate to the test systems,
written records are kept of examination, quarantine, morbidity,
mortality, behaviour, diagnosis and treatment of animal and plant test
systems or other similar aspects as appropriate to each biological test
system,
there are provisions for the appropriate disposal of test systems at the
end of tests.
Test and reference substances
Purpose
to determine whether the test facility has procedures designed -
(i)
to ensure that the identity, potency, quantity and composition of
test and reference substances are in accordance with their
specifications, and
(ii) to properly receive and store test and reference substances.
The inspector should check that
there are written records on the receipt (including identification of the
person responsible), and for the handling, sampling, usage and storage
of tests and reference substances,
test and reference substances containers are properly labelled,
storage conditions are appropriate to preserve the concentration, purity
and stability of the test and reference substances,
there are written records on the determination of identity, purity,
composition, stability, and for the prevention of contamination of test
and reference substances, where applicable,
there are procedures for the determination of the homogeneity and
stability of mixtures containing test and reference substances, where
applicable,
containers holding mixtures (or dilutions) of the test and reference
substances are labelled and that records are kept of the homogeneity and
stability of their contents, where applicable,
GOOD LABORATORY PRACTICE
when the test is of longer than four weeks duration, samples from each
batch of test and reference substances have been taken for analytical
purposes and that they have been retained for an appropriate time,
procedures for mixing substances are designed to prevent errors in
identification or cross-contamination.
Standard operating procedures
Purpose
to determine whether the test facility has written SOPs relating to all
the important aspects of its operations, considering that one of the
most important management techniques for controlling facility
operations is the use of written SOPs. These relate directly to the
routine elements of tests conducted by the test facility.
The inspector should check that
each test facility area has immediately available relevant, authorised
copies of SOPs,
procedures exist for revision and updating of SOPs,
any amendments or changes to SOPs have been authorised and dated,
historical files of SOPs are maintained,
SOPs are available for, but not necessarily limited to, the following
activities
(i)
receipt; determination of identity, purity, composition and
stability; labelling; handling; sampling; usage; and storage of test
and reference substances;
(ii) use, maintenance, cleaning, calibration and validation of
measuring apparatus, computerised systems and environmental
control equipment;
(iii) preparation of reagents and dosing formulations;
(iv) record-keeping, reporting, storage and retrieval of records and
reports;
(v) preparation and environmental control of areas containing the test
systems;
(vi) receipt, transfer, location, characterisation, identification and care
of test systems;
(vii)
handling of the test systems before, during and at the termination
of the study;
(viii) disposal of test systems;
(ix) use of pest control and cleaning agents;
(x)
quality assurance programme operations.
Performance of the study
Purpose
to verify that written study plans exist and that the plans and the
conduct of the study are in accordance with Good Laboratory Practice
principles.
The inspector should check that
the study plan was signed by the study director,
any amendments to the study plan were signed and dated by the study
director,
GOOD LABORATORY PRACTICE
the date of the agreement to the study plan by the sponsor was recorded
(where applicable),
measurements, observations and examinations were in accordance with
the study plan and relevant SOPs,
the results of these measurements, observations and examinations were
recorded directly, promptly, accurately and legibly and were signed (or
initialled) and dated,
any changes in the raw data, including data stored in computers, did not
obscure previous entries, included the reason for the change and
identified the person responsible for the change and the date it was
made,
computer-generated or stored data have been identified and that the
procedures to protect them against unauthorised amendments or loss are
adequate,
the computerised systems used within the study are reliable, accurate
and have been validated,
any unforeseen events recorded in the raw data have been investigated
and evaluated,
the results presented in the reports of the study (interim or final) are
consistent and complete and that they correctly reflect the raw data.
Reporting of study results
Purpose
to determine whether final reports are prepared in accordance with
Good Laboratory Practice principles.
When examining a final report, the inspector should check that
it is signed and dated by the study director to indicate acceptance of
responsibility for the validity of the study and confirming that the study
was conducted in accordance with Good Laboratory Practice principles,
it is signed and dated by other principal scientists, if reports from
cooperating disciplines are included,
a quality assurance statement is included in the report and that it is
signed and dated,
any amendments were made by the responsible personnel,
it lists the archive location of all samples, specimens and raw data.
Storage and retention of records
Purpose
to determine whether the facility has generated adequate records and
reports and whether adequate provision has been made for the safe
storage and retention of records and materials[
The inspector should check
that a person has been identified as responsible for the archive,
the archive facilities for the storage of study plans, raw data (including
that from discontinued Good Laboratory Practice studies), final reports,
samples and specimens and records of education and training of
personnel,
the procedures for retrieval of archived materials,
the procedures whereby access to the archives is limited to authorised
GOOD LABORATORY PRACTICE
personnel and records are kept of personnel given access to raw data,
slides, etc.,
that an inventory is maintained of materials removed from, and returned
to, the archives,
that records and materials are retained for the required or appropriate
period of time and are protected from loss or damage by fire, adverse
environmental conditions, etc.
Study audits
Test facility inspections will generally include, inter alia, study audits, which
review on-going or completed studies. Specific study audits are also often requested
by Regulatory Authorities, and can be conducted independently of test facility
inspections. Because of the wide variation in the types of studies which might be
audited, only general guidance is appropriate, and inspectors and others taking part
in study audits will always need to exercise judgment as to the nature and extent of
their examinations. The objective should be to reconstruct the study by comparing
the final report with the study plan, relevant SOPs, raw data and other archived
In some cases, inspectors may need assistance from other experts in order to
conduct an effective study audit, for example, where there is a need to examine
tissue sections under the microscope.
When conducting a study audit, the inspector should
obtain names, job descriptions and summaries of training and
experience for selected personnel engaged in the study(ies) such as the
study director and principal scientists,
check that there is sufficient staff trained in relevant areas for the
study(ies) undertaken,
identify individual items of apparatus or special equipment used in the
study and examine the calibration, maintenance and service records for
the equipment,
review the records relating to the stability of the test substances,
analyses of test substance and formulations, analyses of feed, etc.,
attempt to determine, through the interview process if possible, the
work assignments of selected individuals participating in the study to
ascertain if these individuals had the time to accomplish the tasks
specified in the study plan or report,
obtain copies of all documentation concerning control procedures or
forming integral parts of the study, including
(i) the study plan;
(ii) SOPs in use at the time the study was done;
(iii) logbooks, laboratory notebooks, files, worksheets, print-outs of
computer-stored data, etc.; checking of calculations, where
appropriate;
(iv) the final report.
In studies in which animals (i.e., rodents and other mammals) are used, the
inspectors should follow a certain percentage of individual animals from their arrival
at the test facility to autopsy. They should pay particular attention to the records
relating to
GOOD LABORATORY PRACTICE
-
animal body weight, food/water intake, dose formulation and
administration, etc.,
-
clinical observations and autopsy findings,
-
clinical chemistry,
-
pathology.
Completion of inspection or study audit
When a test facility inspection or study audit has been completed, the inspector
should be prepared to discuss his findings with representatives of the test facility at a
closing conference and should prepare a written report, i.e., the inspection report.
A test facility inspection of any large facility is likely to reveal a number of minor
deviations from Good Laboratory Practice principles but, normally, these will not be
sufficiently serious to affect the validity of studies emanating from that test facility.
In such cases, it is reasonable for an inspector to report that the facility is operating
in compliance with Good Laboratory Practice principles according to the criteria
established by the (national) Good Laboratory Practice Monitoring Authority.
Nevertheless, details of the inadequacies or faults detected should be provided to the
test facility and assurances sought from its senior management that action will be
taken to remedy them.
The inspector may need to revisit the facility after a period of time to verify that
necessary action has been taken.
If a serious deviation from the Good Laboratory Practice principles is identified
during a test facility inspection or study audit which, in the opinion of the inspector,
may have affected the validity of that study, or of other studies performed at the
facility, the inspector should report back to the (national) Good Laboratory Practice
Monitoring Authority. The action taken by that Authority and/or the Regulatory
Authority, as appropriate, will depend on the nature and extent of the non-
compliance and the legal and, or administrative provisions within the Good
Laboratory Practice compliance programme.
Where a study audit has been conducted at the request of a Regulatory Authority, a
full report of the findings should be prepared and sent via the relevant (national)
Good Laboratory Practice Monitoring Authority.
(1) The National Accreditation Body - Malta Standards
Authority (NAB-MSA), hereinafter referred to as the competent
authority, shall be responsible for verifying compliance with the
principles of Good Laboratory Practice of any testing laboratory in
Malta claiming to use Good Laboratory Practice, as referred to in
regulation 2(1), in the conduct of tests on chemicals.
(2) Should it be established on the basis of detailed evidence
that the application of the principles of Good Laboratory Practice
and the verification of their application for tests on chemical
substances show that, although a chemical substance has been
examined in accordance with the requirements of these regulations,
it presents a danger to man and, or the environment, the Director
responsible for Consumer Affairs may, on the advice of the Head of
the Directorate responsible for chem ical s within the Malta
Standards Authority, provisionally prohibit or make subject to
special conditions the marketing of that substance in Malta.
(3) On a yearly basis, the competent authority shall draw up a
report relating to the implementation of Good Laboratory Practice
in Malta. The report shall contain a list of laboratories inspected,
the date on which such inspection was carried out and a brief
summary of the conclusions of the inspections. The report shall be
forwarded to the European Commission each year, not later than
31st March.
Where a laboratory has carried out a test in accordance
with regulation 2(1), it shall give a notice in writing to the person
GOOD LABORATORY PRACTICE
who commissioned the test and to the competent authority, stating
that the test has been carried out in conformity with the principles
of Good Laboratory Practice.
(1) This regulation shall apply to the inspection and
verification of the organizational processes and the conditions
under which laboratory studies are planned, performed, recorded
and reported for the non-clinical testing, carried out in accordance
with the rules and regulations, of all chemicals (e.g. cosmetics,
industrial chemicals, medicinal products, food additives, animal
feed additives, pesticides) in order to assess the effect of such
products on man, animals and the environment.
(2) This regulation is not concerned with the interpretation and
evaluation of test results.
(3) The compliance with Good Laboratory Practice of any
testing laboratory claiming to use Good Laboratory Practice in the
conduct of tests on chemicals shall be verified using the procedure
laid down in this regulation.
(4) Where the provisions of subregulation (3) have been
complied with, and the results of the inspection and verification are
satisfactory, the competent authority may provide endorsement of a
claim by a laboratory that it and the tests that it carries out comply
with Good Laboratory Practice, using the formula ‘Assessment of
conformity with Good Laboratory Practice according to Directive
2004/9/EC on ........................... (date)’.
(5) The competent authority shall inspect the laboratory and
audit the studies in accordance with the provisions laid down in the
Second Schedule.
(6) The competent authority shall ensure that commercially
sensitive and other confidential information to which it gains
access as a result of Good Laboratory Practice com pliance
monitoring activities is made available only to those national and
international bodies which the Minister may, from time to time,
designate, and to a laboratory or study sponsor directly concerned
with a particular inspection or study audit.
(7) The names of the laboratories subject to inspection by the
competent authority, their Good Laboratory Practice compliance
status and the dates upon which laboratory inspections or study
audits have been conducted shall not be considered to be
confidential.
(1) Without prejudice to subregulation (2), the competent
authority shall accept the results of laboratory inspections and
study audits on Good Laboratory Practice compliance carried out
by Member States of the European Community.
(2) Where the competent authority has sufficient reason to
believe that a laboratory in another Member State claiming Good
Laboratory Practice compliance has not carried out a test according
to Good Laboratory Practice, it may request further information
from the competent authority of that Member State prior to taking a
decision on whether to accept the test results.
GOOD LABORATORY PRACTICE
Standard operating procedures
GOOD LABORATORY PRACTICE
Performance of the study
8.1.
Study plan
8.2.
Content of the study plan
8.3.
Conduct of the study
Reporting of study results
9.1.
General
9.2.
Content of the final report
Storage and retention of records and materials
Section I
INTRODUCTION
Preface
Government and industry are concerned about the quality of non-clinical health
and environmental safety studies upon which hazard assessments are based. As a
consequence, OECD Member countries have established criteria for the performance
of these studies.
To avoid different schemes of implementation that could impede international
trade in chemicals, OECD Member countries have pursued international
harmonisation of test methods and Good Laboratory Practice. In 1979 and 1980 an
international group of experts, established under the special programme on the
control of chemicals, developed the ‘OECD principles of Good Laboratory Practice’
(Good Laboratory Practice), utilising common managerial and scientific practices
and experience from various national and international sources. These principles of
Good Laboratory Practice were adopted by the OECD Council in 1981, as an Annex
to the Council Decision on the mutual acceptance of data in the assessment of
chemicals. [C(81)30(Final)].
In 1995 and 1996, a new group of experts was formed to revise and update the
principles. The current document is the result of the consensus reached by that
group. It cancels and replaces the original principles adopted in 1981.
The purpose of these principles of Good Laboratory Practice is to promote the
development of quality test data. Comparable quality of test data forms the basis for
the mutual acceptance of data among countries. If individual countries can
confidently rely on test data developed in other countries, duplicative testing can be
avoided, thereby saving time and resources. The application of these principles
should help to avoid the creation of technical barriers to trade, and further improve
the protection of human health and the environment.
1. Scope
These principles of Good Laboratory Practice should be applied to the non-clinical
safety testing of test items contained in pharmaceutical products, pesticide products,
cosmetic products, veterinary drugs as well as food additives, feed additives, and
industrial chemicals. These test items are frequently synthetic chemicals, but may be
of natural or biological origin and, in some circumstances, may be living organisms.
The purpose of testing these test items is to obtain data on their properties and, or
their safety with respect to human health and, or the environment.
Non-clinical health and environmental safety studies covered by the principles of
Good Laboratory Practice include work conducted in the laboratory, in greenhouses,
and in the field.
GOOD LABORATORY PRACTICE
Unless specifically exempted by national legislation, these principles of Good
Laboratory Practice apply to all non-clinical health and environmental safety studies
required by regulation for the purpose of registering or licensing pharmaceuticals,
pesticides, food and feed additives, cosmetic products, veterinary drug products and
similar products, and for the regulation of industrial chemicals.
2. Definition of terms
2.1. Good laboratory practice
Go od lab o ra to r y p ra cti ce (G LP) i s a q ua li t y sys tem co nc erne d wi t h t he
organisational process and the conditions under which non-clinical health and
environmental safety studies are planned, performed, monitored, recorded, archived
and reported.
2.2. Terms concerning the organisation of a test facility
1. Test facility means the persons, premises and operational unit(s) that are
necessary for conducting the non-clinical health and environmental
safety study. For multisite studies, those which are conducted at more
than one site, the test facility comprises the site at which the study
director is located and all individual test sites, which individually or
collectively can be considered to be test facilities.
2. Test site means the location(s) at which a phase(s) of a study is
conducted.
3. Test facility management means the person(s) who has the authority and
formal responsibility for the organisation and functioning of the test
facility according to these principles of Good Laboratory Practice.
4. Test site management (if appointed) means the person(s) responsible for
ensuring that the phase(s) of the study, for which he is responsible, are
conducted according to these principles of Good Laboratory Practice.
5. Sponsor means an entity which commissions, supports and, or submits a
non-clinical health and environmental safety study.
6. Study director means the individual responsible for the overall conduct
of the non-clinical health and environmental safety study.
7. Principal investigator means an individual who, for a multisite study,
acts on behalf of the study director and has defined responsibility for
delegated phases of the study. The study director’s responsibility for the
overall conduct of the study cannot be delegated to the principal
investigator(s); this includes approval of the study plan and its
amendments, approval of the final report, and ensuring that all
applicable principles of Good Laboratory Practice are followed.
8. Quality assurance programme: means a defined system, including
personnel, which is independent of study conduct and is designed to
assure test facility management of compliance with these principles of
Good Laboratory Practice.
9. Standard operating procedures (SOPs) means documented procedures
which describe how to perform tests or activities normally not specified
in detail in study plans or test guidelines.
10. Master schedule means a compilation of information to assist in the
assessment of workload and for the tracking of studies at a test facility.
2.3. Terms concerning the non-clinical health and environmental safety study
1. Non-clinical health and environmental safety study, henceforth referred
GOOD LABORATORY PRACTICE
to simply as ‘study’, means an experiment or set of experiments in
which a test item is examined under laboratory conditions or in the
environment to obtain data on its properties and, or its safety, intended
for submission to appropriate regulatory authorities.
2. Short-term study means a study of short duration with widely used,
routine techniques.
3. Study plan means a document which defines the objectives and
experimental design for the conduct of the study, and includes any
amendments.
4. Study plan amendment means an intended change to the study plan after
the study initiation date.
5. Study plan deviation means an unintended departure from the study plan
after the study initiation date.
6. Test system means any biological, chemical or physical system or a
combination thereof used in a study.
7. Raw data means all original test facility records and documentation, or
verified copies thereof, which are the result of the original observations
and activities in a study. Raw data also may include, for example,
photographs, microfilm or microfiche copies, computer readable media,
dictated observations, recorded data from automated instruments, or any
other data storage medium that has been recognised as capable of
providing secure storage of information for a time period as stated in
section 10 below.
8. Specimen means any material derived from a test system for
examination, analysis, or retention.
9. Experimental starting date means the date on which the first study
specific data are collected.
10. Experimental completion date means the last date on which data are
collected from the study.
Study initiation date means the date the study director signs the study
plan.
Study completion date means the date the study director signs the final
report.
2.4. Terms concerning the test item
1. Test item means an article that is the subject of a study.
2. Reference item (`control item’) means any article used to provide a basis
for comparison with the test item.
3. Batch means a specific quantity or lot of a test item or reference item
produced during a defined cycle of manufacture in such a way that it
could be expected to be of a uniform character and should be designated
as such.
4. Vehicle means any agent which serves as a carrier used to mix, disperse,
or solubilise the test item or reference item to facilitate the
administration/application to the test system.
GOOD LABORATORY PRACTICE
Section II
GOOD LABORATORY PRACTICE PRINCIPLES
1. Test facility organisation and personnel
1.1. Test facility management’s responsibilities
1. Each test facility management should ensure that these principles of
Good Laboratory Practice are complied with, in its test facility.
2. At a minimum it should
(a) ensure that a statement exists which identifies the individual(s)
within a test facility who fulfil the responsibilities of management
as defined by these principles of Good Laboratory Practice;
(b) ensure that a sufficient number of qualified personnel, appropriate
facilities, equipment, and materials are available for the timely
and proper conduct of the study;
(c) ensure the maintenance of a record of the qualifications, training,
experience and job description for each professional and technical
individual;
(d) ensure that personnel clearly understand the functions they are to
perform and, where necessary, provide training for these
functions;
(e) ensure that appropriate and technically valid standard operating
procedures are established and followed, and approve all original
and revised standard operating procedures;
(f) ensure that there is a quality assurance programme with
designated personnel and assure that the quality assurance
responsibility is being performed in accordance with these
principles of Good Laboratory Practice;
(g) ensure that for each study an individual with the appropriate
qualifications, training, and experience is designated by the
management as the study director before the study is initiated.
Replacement of a study director should be done according to
established procedures, and should be documented;
(h) ensure, in the event of a multisite study, that, if needed, a
principal investigator is designated, who is appropriately trained,
qualified and experienced to supervise the delegated phase(s) of
the study. Replacement of a principal investigator should be done
according to established procedures, and should be documented;
(i) ensure documented approval of the study plan by the study
director;
(j) ensure that the study director has made the approval study plan
available to the quality assurance personnel;
(k) ensure the maintenance of a historical file of all standard
operating procedures;
(l) ensure that an individual is identified as responsible for the
management of the archive(s);
(m) ensure the maintenance of a master schedule;
(n) ensure that test facility supplies meet requirements appropriate to
their use in a study;
(o) ensure for a multisite study that clear lines of communication
GOOD LABORATORY PRACTICE
exist between the study director, principal investigator(s), the
quality assurance programme(s) and study personnel;
(p) ensure that test and reference items are appropriately
characterised;
(q) establish procedures to ensure that computerised systems are
suitable for their intended purpose, and are validated, operated
and maintained in accordance with these principles of Good
Laboratory Practice.
3. When a phase(s) of a study is conducted at a test site, test site
management (if appointed) will have the responsibilities as defined
above with the following exceptions: 1.1.2(g), (i), (j) and (o).
1.2. Study director’s responsibilites
1. The study director is the single point of study control and has the
responsibility for the overall conduct of the study and for its final
report.
2. These responsibilities should include, but not be limited to, the
following functions. The study director should
(a) approve the study plan and any amendments to the study plan by
dated signature;
(b) ensure that the quality assurance personnel have a copy of the
study plan and any amendments in a timely manner and
communicate effectively with the quality assurance personnel as
required during the conduct of the study;
(c) ensure that study plans and amendments and standard operating
procedures are available to study personnel;
(d) ensure that the study plan and the final report for a multisite study
identify and define the role of any principal investigator(s) and
any test facilities and test sites involved in the conduct of the
study;
(e) ensure that the procedures specified in the study plan are
followed, and assess and document the impact of any deviations
from the study plan on the quality and integrity of the study, and
take appropriate corrective action if necessary; acknowledge
deviations from standard operating procedures during the conduct
of the study;
(f) ensure that all raw data generated are fully documented and
recorded;
(g) ensure that computerised systems used in the study have been
validated;
(h) sign and date the final report to indicate acceptance of
responsibility for the validity of the data and to indicate the extent
to which the study complies with these principles of Good
Laboratory Practice;
(i) ensure that after completion (including termination) of the study,
the study plan, the final report, raw data and supporting material
are archived.
1.3. Principal investigator’s responsibilities
The principal investigator will ensure that the delegated phases of the study are
conducted in accordance with the applicable principles of Good Laboratory Practice.
GOOD LABORATORY PRACTICE
1.4. Study personnel’s responsibilities
1. All personnel involved in the conduct of the study must be
knowledgeable in those parts of the principles of Good Laboratory
Practice which are applicable to their involvement in the study.
2. Study personnel will have access to the study plan and appropriate
standard operating procedures applicable to their involvement in the
study. It is their responsibility to comply with the instructions given in
these documents. Any deviation from these instructions should be
documented and communicated directly to the study director, and, or if
appropriate, the principal investigator(s).
3. All study personnel are responsible for recording raw data promptly and
accurately and in compliance with these principles of Good Laboratory
Practice, and are responsible for the quality of their data.
4. Study personnel should exercise health precautions to minimise risk to
themselves and to ensure the integrity of the study. They should
communicate to the appropriate person any relevant known health or
medical condition in order that they can be excluded from operations
that may affect the study.
2. Quality assurance programme
2.1. General
1. The test facility should have a documented quality assurance
programme to assure that studies performed are in compliance with
these principles of Good Laboratory Practice.
2. The quality assurance programme should be carried out by an individual
or by individuals designated by and directly responsible to management
and who are familiar with the test procedures.
3. This individual(s) should not be involved in the conduct of the study
being assured.
2.2. Responsibilities of the quality assurance personnel
The responsibilities of the quality assurance personnel include, but are not
limited to, the following functions. They should
(a) maintain copies of all approved study plans and standard operating
procedures in use in the test facility and have access to an up-to-date
copy of the master schedule;
(b) verify that the study plan contains the information required for
compliance with these principles of Good Laboratory Practice. This
verification should be documented;
(c) conduct inspections to determine if all studies are conducted in
accordance with these principles of Good Laboratory Practice.
Inspections should also determine that study plans and standard
operating procedures have been made available to study personnel and
are being followed.
Inspections can be of three types as specified by quality assurance
programme standard operating procedures
-
study-based inspections,
-
facility-based inspections,
-
process-based inspections.
GOOD LABORATORY PRACTICE
Records of such inspections should be retained;
(d) inspect the final reports to confirm that the methods, procedures, and
observations are accurately and completely described, and that the
reported results accurately and completely reflect the raw data of the
studies;
(e) promptly report any inspection results in writing to management and to
the study director, and to the principal investigator(s) and the respective
management, when applicable;
(f)
prepare and sign a statement, to be included with the final report, which
specifies types of inspections and their dates, including the phase(s) of
the study inspected, and the dates inspection results were reported to
management and the study director and principal investigator(s), if
applicable. This statement would also serve to confirm that the final
report reflects the raw data.
3. Facilities
3.1. General
1. The test facility should be of suitable size, construction and location to
meet the requirements of the study and to minimise disturbance that
would interfere with the validity of the study.
2. The design of the test facility should provide an adequate degree of
separation of the different activities to assure the proper conduct of each
study.
3.2. Test system facilities
1. The test facility should have a sufficient number of rooms or areas to
assure the isolation of test systems and the isolation of individual
projects, involving substances or organisms known to be or suspected of
being biohazardous.
2. Suitable rooms or areas should be available for the diagnosis, treatment
and control of diseases, in order to ensure that there is no unacceptable
degree of deterioration of test systems.
3. There should be storage rooms or areas as needed for supplies and
equipment. Storage rooms or areas should be separated from rooms or
areas housing the test systems and should provide adequate protection
against infestation, contamination, and, or deterioration.
3.3. Facilities for handling test and reference items
1. To prevent contamination or mix-ups, there should be separate rooms or
areas for receipt and storage of the test and reference items, and mixing
of the test items with a vehicle.
2. Storage rooms or areas for the test items should be separate from rooms
or areas containing the test systems. They should be adequate to
preserve identity, concentration, purity, and stability, and ensure safe
storage for hazardous substances.
3.4. Archive facilities
Archive facilities should be provided for the secure storage and retrieval of
study plans, raw data, final reports, samples of test items and specimens. Archive
design and archive conditions should protect contents from untimely deterioration.
3.5. Waste disposal
GOOD LABORATORY PRACTICE
Handling and disposal of wastes should be carried out in such a way as not
to jeopardise the integrity of studies. This includes provision for appropriate
collection, storage and disposal facilities, and decontamination and transportation
procedures.
4. Apparatus, material, and reagents
1. Apparatus, including validated computerised systems, used for the
generation, storage and retrieval of data, and for controlling environmental factors
relevant to the study should be suitably located and of appropriate design and
adequate capacity.
2. Apparatus used in a study should be periodically inspected, cleaned,
maintained, and calibrated according to standard operating procedures. Records of
these activities should be maintained. Calibration should, where appropriate, be
traceable to national or international standards of measurement.
3. Apparatus and materials used in a study should not interfere adversely with
the test systems.
4. Chemicals, reagents, and solutions should be labelled to indicate identity
(with concentration if appropriate), expiry date and specific storage instructions.
Information concerning source, preparation date and stability should be available.
The expiry date may be extended on the basis of documented evaluation or analysis.
5. Test systems
5.1. Physical/chemical
1. Apparatus used for the generation of physical/chemical data should be
suitably located and of appropriate design and adequate capacity.
2. The integrity of the physical/chemical test systems should be ensured.
5.2. Biological
1. Proper conditions should be established and maintained for the storage,
housing, handling and care of biological test systems, in order to ensure
the quality of the data.
2. Newly received animal and plant test systems should be isolated until
their health status has been evaluated. If any unusual mortality or
morbidity occurs, this lot should not be used in studies and, when
appropriate, should be humanely destroyed. At the experimental starting
date of a study, test systems should be free of any disease or condition
that might interfere with the purpose or conduct of the study. Test
systems that become diseased or injured during the course of a study
should be isolated and treated, if necessary to maintain the integrity of
the study. Any diagnosis and treatment of any disease before or during a
study should be recorded.
3. Records of source, date of arrival, and arrival condition of test systems
should be maintained.
4. Biological test systems should be acclimatised to the test environment
for an adequate period before the first administration/application of the
test or reference item.
5. All information needed to properly identify the test systems should
appear on their housing or containers. Individual test systems that are to
be removed from their housing or containers during the conduct of the
study should bear appropriate identification, wherever possible.
GOOD LABORATORY PRACTICE
6. During use, housing or containers for test systems should be cleaned
and sanitised at appropriate intervals. Any material that comes into
contact with the test system should be free of contaminants at levels that
would interfere with the study. Bedding for animals should be changed
as required by sound husbandry practice. Use of pest control agents
should be documented.
7. Test systems used in field studies should be located so as to avoid
interference in the study from spray drift and from past usage of
pesticides.
6. Test and reference items
6.1. Receipt, handling, sampling and storage
1. Records including test item and reference item characterisation, date of
receipt, expiry date, quantities received and used in studies should be
maintained.
2. Handling, sampling, and storage procedures should be identified in
order that the homogeneity and stability are assured to the degree
possible and contamination or mix-up are precluded.
3. Storage container(s) should carry identification information, expiry
date, and specific storage instructions.
6.2. Characterisation
1. Each test and reference item should be appropriately identified (e.g.
code, chemical abstracts service registry number (CAS number), name,
biological parameters).
2. For each study, the identity, including batch number, purity,
composition, concentrations, or other characteristics to appropriately
define each batch of the test or reference items should be known.
3. In cases where the test item is supplied by the sponsor, there should be a
mechanism, developed in cooperation between the sponsor and the test
facility, to verify the identity of the test item subject to the study.
4. The stability of test and reference items under storage and test
conditions should be known for all studies.
5. If the test item is administered or applied in a vehicle, the homogeneity,
concentration and stability of the test item in that vehicle should be
determined. For test items used in field studies (e.g. tank mixes), these
may be determined through separate laboratory experiments.
6. A sample for analytical purposes from each batch of test item should be
retained for all studies except short-term studies.
7. Standard operating procedures
1. A test facility should have written standard operating procedures approved
by test facility management that are intended to ensure the quality and integrity of
the data generated by that test facility. Revisions to standard operating procedures
should be approved by test facility management.
2. Each separate test facility unit or area should have immediately available
current standard operating procedures relevant to the activities being performed
therein. Published text books, analytical methods, articles and manuals may be used
as supplements to these standard operating procedures.
3. Deviations from standard operating procedures related to the study should
GOOD LABORATORY PRACTICE
be documented and should be acknowledged by the study director and the principal
investigator(s), as applicable.
4. Standard operating procedures should be available for, but not be limited to,
the following categories of test facility activities. The details given under each
heading are to be considered as illustrative examples.
1. Test and reference items
Receipt, identification, labelling, handling, sampling and storage.
2. Apparatus, materials and reagents
(a) Apparatus
use, maintenance, cleaning and calibration.
(b) Computerised systems
validation, operation, maintenance, security, change control and
back-up.
(c) Materials, reagents and solutions
preparation and labelling.
3. Record keeping, reporting, storage, and retrieval
Coding of studies, data collection, preparation of reports, indexing
systems, handling of data, including the use of computerised systems.
4. Test system (where appropriate)
(a) Room preparation and environmental room conditions for the test
system.
(b) Procedures
for
receipt,
transfer,
proper
placement,
characterisation, identification and care of the test system.
(c) Test system preparation, observations and examinations, before,
during and at the conclusion of the study.
(d) Handling of test system individuals found moribund or dead
during the study.
(e) Collection, identification and handling of specimens including
necropsy and histopathology.
(f) Siting and placement of test systems in test plots.
5. Quality assurance procedures Operation of Quality Assurance personnel
in planning, scheduling, performing, documenting and reporting
inspections.
8. Performance of the study
8.1. Study plan
1. For each study, a written plan should exist prior to the initiation of the
study. The study plan should be approved by dated signature of the
study director and verified for Good Laboratory Practice compliance by
quality assurance personnel as specified in 2.2(b) of Section II. The
study plan should also be appproved by the test facility management
and the sponsor, if required by national regulation or legislation in the
country where the study is being performed.
2. (a) Amendments to the study plan should be justified and approved
by dated signature of the study director and maintained with the
study plan.
(b) Deviations from the study plan should be described, explained,
GOOD LABORATORY PRACTICE
acknowledged and dated in a timely fashion by the study director
and, or principal investigator(s) and maintained with the study
raw data.
3. For short-term studies, a general study plan accompanied by a study
specific supplement may be used.
8.2. Content of the study plan
The study plan should contain, but not be limited to the following
1. Identification of the study, the test item and reference item
(a) a descriptive title;
(b) a statement which reveals the nature and purpose of the study;
(c) identification of the test item by code or name (IUPAC; CAS
number, biological parameters, etc.);
(d) the reference item to be used.
2. Information concerning the sponsor and the test facility
(a)
name and address of the sponsor;
(b)
name and address of any test facilities and test sites involved;
(c)
name and address of the study director;
(d)
name and address of the principal investigator(s), and the phase(s)
of the study delegated by the study director and under the
responsibility of the principal investigator(s).
3. Dates
(a) the date of approval of the study plan by signature of the study
director. The date of approval of the study plan by signature of the
test facility management and sponsor if required by national
regulation or legislation in the country where the study is being
performed;
(b) the proposed experimental starting and completion dates.
4. Test methods
Reference to the OECD test guideline or other test guideline or method
to be used.
5. Issues (where applicable)
(a) the justification for selection of the test system;
(b) characterisation of the test system, such as the species, strain,
substrain, source of supply, number, body weight range, sex, age
and other pertinent information;
(c) the method of administration and the reason for its choice;
(d) the dose levels and, or concentration(s), frequency, and duration
of administration/application;
(e) detailed information on the experimental design, including a
description of the chronological procedure of the study, all
methods, materials and conditions, type and frequency of
analysis, measurements, observations and examinations to be
performed, and statistical methods to be used (if any).
6. Records
a list of records to be retained.
GOOD LABORATORY PRACTICE
8.3. Conduct of the study
1. A unique identification should be given to each study. All items
concerning this study should carry this identification. Specimens from
the study should be identified to confirm their origin. Such
identification should enable traceability, as appropriate for the specimen
and study.
2. The study should be conducted in accordance with the study plan.
3. All data generated during the conduct of the study should be recorded
directly, promptly, accurately, and legibly by the individual entering the
data. These entries should be signed or initialled and dated.
4. Any change in the raw data should be made so as not to obscure the
previous entry, should indicate the reason for change and should be
dated and signed or initialled by the individual making the change.
5. Data generated as a direct computer input should be identified at the
time of data input by the individual(s) responsible for direct data
entries. Computerised system design should always provide for the
retention of full audit trails to show all changes to the data without
obscuring the original data. It should be possible to associate all
changes to data with the persons having made those changes, for
example, by use of timed and dated (electronic) signatures. Reason for
changes should be given.
9. Reporting of study results
9.1. General
1. A final report should be prepared for each study. In the case of short-
term studies, a standardized final report accompanied by a study
specific extension may be prepared.
2. Reports of principal investigators or scientists involved in the study
should be signed and dated by them.
3. The final report should be signed and dated by the study director to
indicate acceptance of responsibility for the validity of the data. The
extent of compliance with these principles of Good Laboratory Practice
should be indicated.
4. Corrections and additions to a final report should be in the form of
amendments. Amendments should clearly specify the reason for the
corrections or additons and should be signed and dated by the study
director.
5. Reformatting of the final report to comply with the submission
requirements of a national registration or regulatory authority does not
constitute a correction, addition or amendment to the final report.
9.2. Content of the final report
The final report should include, but not be limited to, the following
information
1. Identification of the study, the test item and reference item
(a) a descriptive title;
(b) identification of the test item by code or name (IUPAC, CAS
number, biological parameters, etc.);
(c) identification of the reference item by name;
GOOD LABORATORY PRACTICE
(d) characterisation of the test item including purity, stability and
homogeneity.
2. Information concerning the sponsor and the test facility
(a)
name and address of the sponsor;
(b)
name and address of any test facilities and test sites involved;
(c)
name and address of the study director;
(d)
name and address of the principal investigator(s) and the phase(s)
of the study delegated, if applicable;
(e) name and address of scientists having contributed reports to the
final report.
3. Dates
experimental starting and completion dates.
4. Statement
a quality assurance programme statement listing the types of inspections
made and their dates, including the phase(s) inspected, and the dates
any inspection results were reported to management and to the study
director and principal investigator(s), if applicable. This statement
would also serve to confirm that the final report reflects the raw data.
5. Description of materials and test methods
(a) description of methods and materials used;
(b) reference to OECD test guideline or other test guideline or
method.
6. Results
(a) a summary of results;
(b) all information and data required by the study plan;
(c) a presentation of the results, including calculations and
determinations of statistical significance;
(d) an evaluation and discussion of the results and, where
appropriate, conclusions.
7. Storage
the location(s) where the study plan, samples of test and reference
items, specimens, raw data and the final report are to be stored.
10. Storage and retention of records and materials
10.1 The following should be retained in the archives for the period specified by
the appropriate authorities
(a) the study plan, raw data, samples of test and reference items, specimens,
and the final report of each study;
(b) Records of all inspections performed by the quality assurance
programme, as well as master schedules;
(c) records of qualifications, training, experience and job descriptions of
personnel;
(d) records and reports of the maintenance and calibration of apparatus;
(e) validation documentation for computerised systems;
(f)
the historical file of all standard operating procedures;
GOOD LABORATORY PRACTICE
(g) environmental monitoring records. In the absence of a required
retention period, the final disposition of any study materials should be
documented. When samples of test and reference items and specimens
are disposed of before the expiry of the required retention period for any
reason, this should be justified and documented. Samples of test and
reference items and specimens should be retained only as long as the
quality of the preparation permits evaluation.
10.2. Material retained in the archives should be indexed so as to facilitate orderly
storage and retrieval.
10.3. Only personnel authorised by management should have access to the
archives. Movement of material in and out of the archives should be properly
recorded.
10.4. If a test facility or an archive contracting facility goes out of business and
has no legal successor, the archive should be transferred to the archives of the
sponsor(s) of the study(s).