This document is meant purely as documentation tool and the institutions do not assume any liability for its contents
"BCOUNCIL DIRECTIVE
of 18 December 1986
on the harmonization of laws, regulations and administrative provisions relating to the application of
the principles of good laboratory practice and the verification of their applications for tests on
chemical substances
(87/18/EEC)
(OJ L 15, 17.1.1987, p. 29)
Amended by:
Official Journal
No page date
"M1 Commission Directive 1999/11/EC of 8 March 1999 L 77 8 23.3.19991987L0018 — EN — 12.04.1999 — 001.001 — 1
COUNCIL DIRECTIVE
of 18 December 1986
on the harmonization of laws, regulations and administrative
provisions relating to the application of the principles of good
laboratory practice and the verification of their applications for tests
on chemical substances
(87/18/EEC)
THE COUNCIL OF THE EUROPEAN COMMUNITIES,
Having regard to the Treaty establishing the European Economic
Community, and in particular Article 100 thereof,
Having regard to the proposal from the Commission,Having regard to the opinion of the European Parliament (
1),
Having regard to the opinion of the Economic and Social Committee (2),
Whereas Council Directive 67/548/EEC of 27 June 1967 on the
approximation of laws, regulations and administrative provisions relating
to the classification, packaging and labelling of dangerous substances (3),
as last amended by Directive 84/449/EEC (4), requires tests to be carried
out on chemical substances in order to enable their potential risk to man
and the environment to be determined;
Whereas Directive 75/318/EEC (5)a sa m e n d e db yD i r e c t i v e
87/19/EEC (6), and Directive 81/852/EEC (7) as amended by Directive
87/20/EEC (8) lay down that non-clinical tests on pharmaceutical
products shall be carried out in accordance with the principles of good
laboratory practice in force in the Community for chemical substances;
Whereas when the active substances in pesticides undergo tests they shall
do so in accordance with the protocols provided for by Directive
67/548/EEC, and hence in accordance with good laboratory practice for
chemical substances;
Whereas the methods to be used for these tests are laid down in Annex V
to Directive 67/548/EEC;
Whereas it is necessary to comply with the principles of good laboratory
practice in carrying out the tests laid down by Directive 67/548/EEC so
as to ensure that the results are comparable and of high quality;
Whereas the Commission intends shortly to submit a proposal to the
Council for a Directive aiming at verifying compliance with the
principles of good laboratory practice;
Whereas the resources devoted to the tests must not be wasted by having
to repeat tests owing to differences in laboratory practice from one
Member State to another;
Whereas the Council of the Organization for Economic Cooperation and
Development (OECD) took a Decision on 12 May 1981 on the mutual
acceptance of data for the evaluation of chemical products; whereas it
issued a recommendation on 26 July 1983 concerning the mutual
recognition of compliance with good laboratory practice;!B
(1) OJ No C 120, 20. 5. 1986, p. 177.
(2) OJ No C 354, 31. 12. 1985, p. 5.
(3) OJ No 196, 16. 8. 1967, p. 1.
(4) OJ No L 251, 19. 9. 1984, p. 1.
(5) OJ No L 147, 9. 6. 1975, p. 1.
(6) See page 31 of this Official Journal.
(7) OJ No L 317, 6. 11. 1981, p. 16.
(8) See page 34 of this Official Journal.1987L0018 — EN — 12.04.1999 — 001.001 — 2
Whereas animal protection requires that the number of experiments
conducted on animals be restricted; whereas mutual recognition of the
results of tests obtained using standard and recognized methods is an
essential condition for reducing the number of experiments in this area;
Whereas it is necessary to set up a procedure allowing rapid adaptation
of the principles of good laboratory practice,
HAS ADOPTED THIS DIRECTIVE:
Article 1
1. Member States shall take all measures necessary to ensure that
laboratories carrying out tests on chemical products, in accordance with
Directive 67/548/EEC, comply with the principles of good laboratory
practice as laid down in the Annex to this Directive.
2. Paragraph 1 shall apply also where other Community 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.
Article 2
When submitting results, the laboratories referred to in Article 1 must
certify that the tests have been carried out in conformity with the
principles of good laboratory practice referred to in that Article.
Article 3
1. Member States shall adopt the measures necessary for verification of
compliance with the principles of good laboratory practice. These
measures shall include, in particular, inspections and study checks in
accordance with the recommendations of the OECD in this area.
2. Member States shall notify to the Commission the name or names of
the authority or authorities responsible for verifying compliance with the
principles of good laboratory practice, as referred to in paragraph 1. The
Commission shall inform the other Member States thereof.
Article 4
Adaptations to the principles of good laboratory practice mentioned in
Article 1 may be adopted in accordance with the procedure laid down in
Article 21 of Directive 67/548/EEC.
Article 5
1. Where Community provisions require application of the principles of
good laboratory practice following the entry into force of this Directive
for tests on chemical products, Member States may not, on grounds
relating to the principles of good laboratory practice, prohibit, restrict or
impede the placing on the market of chemical products if the principles
applied by the laboratories concerned are in conformity with those
mentioned in Article 1.
2. Should a Member State establish 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 this Directive, it presents a danger to man and
the environment, the Member State may provisionally prohibit or make
subject to special conditions the marketing of that substance on its
territory. It shall immediately inform the Commission and the other
Member States thereof and give the grounds for its decision.!B
!M1
!B1987L0018 — EN — 12.04.1999 — 001.001 — 3
The Commission shall, within six weeks, consult the Member States
concerned and then give its opinion and take suitable measures without
delay.
Should the Commission consider that technical adaptations to this
Directive are necessary, those adaptations shall be adopted either by the
Commission or by the Council in accordance with the procedure laid
down in Article 4. In that case, the Member State which adopted the
safeguard measures may maintain them until entry into force of those
adaptations.
Article 6
Member States shall bring into force the laws, regulations and
administrative provisions necessary to comply with this Directive not
later than 30 June 1988. They shall forthwith inform the Commission
thereof.
Article 7
This Directive is addressed to the Member States.!B1987L0018 — EN — 12.04.1999 — 001.001 — 4
ANNEX
THE OECD PRINCIPLES OF GOOD LABORATORY PRACTICE (GLP)
Contents
Section IINTRODUCTION
Preface
1. Scope
2. Definitions of terms
2.1. Good laboratory practice
2.2. Terms concerning the organisation of a test facility2.3. Terms concerning the non-clinical health and environmental safety study
2.4. Terms concerning the test item
Section II
GOOD LABORATOR Y 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 responsibilities1.4. Study personnel’ s responsibilities
2. Quality assurance programme
2.1. General2.2. Responsibilities of the quality assurance personnel
3. Facilities
3.1. General3.2. Test system facilities
3.3. Facilities for handling test and reference items
3.4. Archive facilities3.5. Waste disposal
4. Apparatus, material, and reagents
5. Test systems
5.1. Physical/chemical5.2. Biological
6. Test and reference items
6.1. Receipt, handling, sampling and storage6.2. Characterisation
7. Standard operating procedures
8. Performance of the study
8.1. Study plan
8.2. Content of the study plan
8.3. Conduct of the study
9. Reporting of study results
9.1. General
9.2. Content of the final report!
M11987L0018 — EN — 12.04.1999 — 001.001 — 5
10. 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 aconsequence, OECD Member countries have established criteria for theperformance 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 thecontrol of chemicals, developed the ‘OECD principles of good laboratorypractice’ (GLP), utilising common managerial and scientific practices and
experience from various national and international sources. These principles of
GLP were adopted by the OECD Council in 1981, as an Annex to the CouncilDecision 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 basisfor the mutual acceptance of data among countries. If individual countries canconfidently 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 improvethe 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, pesticideproducts, 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 dataon 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 green-
houses, and in the field.
Unless specifically exempted by national legislation, these principles of good
laboratory practice apply to all non-clinical health and environmental safetystudies required by regulation for the purpose of registering or licensingpharmaceuticals, 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
Good laboratory practice (GPL) is a quality system concerned with the
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 environ-mental 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, whichindividually or collectively can be considered to be test facilities.!
M11987L0018 — EN — 12.04.1999 — 001.001 — 6
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 principalinvestigator(s); this includes approval of the study plan and itsamendments, 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 toassure 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 notspecified 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 testfacility.
2.3. Terms concerning the non-clinical health and environmental safety study
1. Non-clinical health and environmental safety study, henceforth
referred to simply as ‘study’, means an experiment or set ofexperiments 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 auth-orities.
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 anyamendments.
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 originalobservations 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 automatedinstruments, or any other data storage medium that has beenrecognised 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.!
M11987L0018 — EN — 12.04.1999 — 001.001 — 7
11. Study initiation date means the date the study director signs the study
plan.
12. 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 theadministration/application to the test system.
Section II
GOOD LABORATOR Y 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 manage-ment as defined by these principles of good laboratory practice;
(b) ensure that a sufficient number of qualified personnel, appropri-
ate 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 thesefunctions;
(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 theseprinciples 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 toestablished 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;!
M11987L0018 — EN — 12.04.1999 — 001.001 — 8
(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
exist between the study director, principal investigator(s), thequality assurance programme(s) and study personnel;
(p) ensure that test and reference items are appropriately char-
acterised;
(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 goodlaboratory 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 definedabove 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 andcommunicate 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 thestudy;
(e) ensure that the procedures specified in the study plan are
followed, and assess and document the impact of any deviationsfrom 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 theconduct 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 goodlaboratory practice.!
M11987L0018 — EN — 12.04.1999 — 001.001 — 9
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 laboratorypractice 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 bedocumented and communicated directly to the study director, and/or ifappropriate, 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 shouldcommunicate to the appropriate person any relevant known health ormedical 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 tomanagement 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-datecopy 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 standardoperating 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.
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 thestudies;
(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 thephase(s) of the study inspected, and the dates inspection results were!
M11987L0018 — EN — 12.04.1999 — 001.001 — 10
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 ofeach 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 nounacceptable 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, andmixing 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 fromuntimely deterioration.
3.5. Waste disposal
Handling and disposal of wastes should be carried out in such a way as not
to jeopardise the integrity of studies. This includes provision forappropriate collection, storage and disposal facilities, and decontaminationand transportation procedures.
4.Apparatus, material, and reagents
1. Apparatus, including validated computerised systems, used for the
generation, storage and retrieval of data, and for controllingenvironmental 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 pro-cedures. Records of these activities should be maintained. Calibrationshould, 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 specificstorage instructions. Information concerning source, preparation date!
M11987L0018 — EN — 12.04.1999 — 001.001 — 11
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 ormorbidity 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 orcondition that might interfere with the purpose or conduct of thestudy. 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 diseasebefore 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 areto be removed from their housing or containers during the conduct ofthe study should bear appropriate identification, wherever possible.
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 levelsthat would interfere with the study. Bedding for animals should bechanged 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 ofpesticides.
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 shouldbe 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 appropriatelydefine each batch of the test or reference items should be known.!
M11987L0018 — EN — 12.04.1999 — 001.001 — 12
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 laboratoryexperiments.
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 thequality 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 theactivities 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 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. Thedetails 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 ofcomputerised systems.
4. Test system (where appropriate)
(a) Room preparation and environmental room conditions for
the test system.
(b) Procedures for receipt, transfer, proper placement, char-
acterisation, 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 includ-
ing necropsy and histopathology.
(f) Siting and placement of test systems in test plots.
5. Quality assurance procedures!
M11987L0018 — EN — 12.04.1999 — 001.001 — 13
Operation of Quality Assurance personnel in planning, schedul-
ing, 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 GLP compliance by quality assurance
personnel as specified in 2.2(b) of Section II. The study plan shouldalso be appproved by the test facility management and the sponsor, ifrequired by national regulation or legislation in the country where the
study is being performed.
2. 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,
acknowledged and dated in a timely fashion by the study director
and/or principal investigator(s) and maintained with the studyraw 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
information:
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 underthe 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 ofthe test facility management and sponsor if required by nationalregulation 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;!
M11987L0018 — EN — 12.04.1999 — 001.001 — 14
(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 beperformed, and statistical methods to be used (if any).
6. Records:
a list of records to be retained.
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 thespecimen 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 theretention of full audit trails to show all changes to the data withoutobscuring 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 forchanges 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 standardised final report accompanied by a studyspecific 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. Theextent 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;
(d) characterisation of the test item including purity, stability and
homogeneity.!
M11987L0018 — EN — 12.04.1999 — 001.001 — 15
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 andto 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 deter-
minations of statistical significance;
(d) an evaluation and discussion of the results and, where appropri-
ate, 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;(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 onlyas 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.!
M11987L0018 — EN — 12.04.1999 — 001.001 — 16
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).!M11987L0018 — EN — 12.04.1999 — 001.001 — 17