Proposal for a Directive of the European Parliament and of the Council on the harmonisation 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 (codified version)
Date: 2002-09-26
Institutions: European Commission
Subjects: OECD, approximation of laws, chemical product, codification of EU law, environmental risk prevention, health control, research body, testing

COMMISSION OF THE EUROPEAN COMMUNITIES

Brussels, 26.09.2002
COM(2002) 530 final

2002/0231 (COD)

Proposal for a

DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

on the harmonisation 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

(codified version)

(presented by the Commission)

1.

2.

3.

4.

1

2

3

4

EXPLANATORY MEMORANDUM

In the context of a people’s Europe, the Commission attaches great importance to
simplifying and clarifying Community law so as to make it clearer and more
accessible to the ordinary citizen, thus giving him new opportunities and the chance
to make use of the specific rights it gives him.

This aim cannot be achieved so long as numerous provisions that have been amended
several times, often quite substantially, remain scattered, so that they must be sought
partly in the original instrument and partly in later amending ones. Considerable
research work, comparing many different instruments, is thus needed to identify the
current rules.

For this reason a codification of rules that have frequently been amended is also
essential if Community law is to be clear and transparent.

On 1 April 1987 the Commission therefore decided1 to instruct its staff that all
legislative measures should be codified after no more than ten amendments, stressing
that this was a minimum requirement and that departments should endeavour to
codify at even shorter intervals the texts for which they are responsible, to ensure that
the Community rules were clear and readily understandable.

The Conclusions of the Presidency of the Edinburgh European Council (December
1992) confirmed this2, stressing the importance of codification as it offers certainty
as to the law applicable to a given matter at a given time.

Codification must be undertaken in full compliance with the normal Community
legislative procedure.

Given that no changes of substance may be made to the instruments affected by
codification, the European Parliament, the Council and the Commission have agreed,
by an interinstitutional agreement dated 20 December 1994, that an accelerated
procedure may be used for the fast-track adoption of codification instruments.

this proposal3

is to undertake the codification of Council
The purpose of
Directive 87/18/EEC of 18 December 1986, on the harmonisation of
laws,
regulations and administrative provisions relating to the principles of good laboratory
practice and the verification of their applications for tests on chemical substances.
The new Directive will supersede the various Directives incorporated in it4; their
content is fully preserved, and they are brought together with only such formal
amendments as are required by the codification exercise itself.

COM(1987) 868 PV.
See Annex 3 to Part A of such conclusions.
Carried out pursuant to the Communication from the Commission to the European Parliament and the
Council – Codification of the Acquis communautaire, COM(2001) 645 final.
See Annex II, Part A of this proposal.

2

5.

The codification proposal was drawn up on the basis of a preliminary consolidation,
in all official languages, of Directive 87/18/EEC and the instruments amending it,
carried out by the Office of Official Publications of the European Communities, by
means of a data-processing system. Insofar as the Articles have been given new
numbers, the correlation between the old and the new numbers is shown in a table
contained in Annex III to the codified Directive.

3

(cid:1)

87/18/EEC

Proposal for a

DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

on the harmonisation 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

(Text with EEA relevance)

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,

(cid:1)

87/18/EEC (adapted)

Having regard to the Treaty establishing the European Community, and in particular
Article 95 thereof,

Having regard to the proposal from the Commission,

Having regard to the opinion of the Economic and Social Committee1,

Acting in accordance with the procedure laid down in Article 251 of the Treaty2,

Whereas:

(cid:1)

(1)

Council Directive 87/18/EEC of 18 December 1986 on the harmonisation of laws,
regulations and administrative provisions relating to the application of principles of
good laboratory practice and the verification of their applications for tests on chemical
substances3 has been substantially amended4. In the interests of clarity and rationality
the said Directive should be codified.

1

2

3

4

OJ C , , p. .
OJ C , , p. .
OJ L 15, 17. 1. 1987, p. 29. Directive amended by Commission Directive 1999/11/EC (OJ L 77, 23.3.1999, p. 8).
See Annex II, Part A.

4

(cid:1)

87/18/EEC Recital (1)

(2)

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 substances5 requires tests to be carried out on chemical
substances in order to enable their potential risk to man and the environment to be
determined.

(3) When the active substances in pesticides undergo tests they should do so in

accordance with Directive 67/548/EEC.

(cid:1)

87/18/EEC Recital (3)

(adapted)

(cid:1)

87/18/EEC Recital (2)

(adapted)

(4)

2001/82/EC of

the European Parliament

Directive
the Council
of 6 November 2001 on the Community code relating to veterinary medicinal
products6 and Directive 2001/83/EC of the European Parliament and of the Council
of 6 November 2001 on the Community code relating to medicinal products for human
use7 lay down that non-clinical tests on pharmaceutical products are to be carried out
in accordance with the principles of good laboratory practice (GLP) in force in the
Community for chemical substances, compliance with which is also required by other
Community legislation.

and

of

(5)

The methods
Directive 67/548/EEC.

to be used for

these tests are laid down in Annex V to

(cid:1)

87/18/EEC Recital (4)

(6)

It is necessary to comply with the principles of GLP 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.

(cid:1)

87/18/EEC Recital (5)

5

6

7

OJ 196, 16. 8. 1967, p. 1. Directive as last amended by Commission Directive 2001/59/EC (OJ L 225,
21. 8. 2001, p.1).
OJ L 311, 28. 11. 2001, p. 1.
OJ L 311, 28. 11. 2001, p. 67.

5

(7)

The resources devoted to the tests should not be wasted by having to repeat tests
owing to differences in laboratory practice from one Member State to another.

(cid:1)

87/18/EEC Recital (7)

(cid:1)
(cid:2)

87/18/EEC Recital (8)
1 1999/11/EC recital (1)

(adapted)

(8)

(9)

The Council of the Organisation 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; it issued a recommendation on 26 July 1983 concerning the
mutual recognition of compliance with GLP;
1 the principles of GLP have been
modified by OECD Council Decision [C(97) 186 (Final)].

(cid:3)

(cid:2)

(cid:1)

87/18/EEC Recital (9)

Animal protection requires that the number of experiments conducted on animals be
restricted; mutual recognition of the results of tests obtained using standard and
recognised methods is an essential condition for reducing the number of experiments
in this area.

(10)

It is necessary to set up a procedure allowing rapid adaptation of the principles
of GLP.

(cid:1)

87/18/EEC recital (10)

(cid:1)

(11)

This Directive should be without prejudice to the obligations of the Member States
concerning the time-limits for transposition of the Directives set out in Annex II,
Part B,

HAVE ADOPTED THIS DIRECTIVE:

6

87/18/EEC, Art. 1

Article 1

(cid:1)

(cid:1)

1.

2.

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 (GLP) as laid down in Annex I to this
Directive.

1999/11/EC, Art. 1 (adapted)

(cid:1)

87/18/EEC, Art.1(2)

Paragraph 1 shall apply also where other Community provisions provide for the
application of the principles of GLP in respect of tests on chemical products to
evaluate their safety for man and/or the environment.

(cid:1)

87/18/EEC, Art. 2 (adapted)

Article 2

When submitting results, the laboratories referred to in Article 1 shall certify that the tests
have been carried out in conformity with the principles of GLP referred to in that Article.

(cid:1)

87/18/EEC, Art. 3

Article 3

1.

2.

Member States shall adopt the measures necessary for verification of compliance
with the principles of GLP. These measures shall include, in particular, inspections
and study checks in accordance with the recommendations of the OECD in this area.

Member States shall notify to the Commission the name or names of the authority or
authorities responsible for verifying compliance with the principles of GLP, as
referred to in paragraph 1. The Commission shall inform the other Member States
thereof.

7

(cid:1)

87/18/EEC, Art. 4 (adapted)

Article 4

Any adaptation to the principles of GLP mentioned in Article 1 shall be adopted in
accordance with the procedure referred to in Article 29 of Directive 67/548/EEC.

(cid:1)

87/18/EEC, Art. 5

Article 5

1.

2.

Where Community provisions require application of the principles of GLP following
the entry into force of this Directive for tests on chemical products, Member States
may not, on grounds relating to the principles of GLP, 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.

Should a Member State establish on the basis of detailed evidence that
the
application of the principles of GLP 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
It shall
immediately inform the Commission and the other Member States thereof and give
the grounds for its decision.

that substance on its territory.

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 referred to in Article 4. In that case, the
Member State which adopted the safeguard measures may maintain them until the
entry into force of those adaptations.

(cid:1)

Article 6

Directive 87/18/EEC, as amended by the Directive set out in Annex II, Part A, is hereby
repealed, without prejudice to the obligations of the Member States concerning the time-limits
for transposition of the said Directive as set out in Annex II, Part B.

References to the repealed Directive shall be construed as references to this Directive and
shall be read in accordance with the correlation table set out in Annex III.

8

This Directive shall enter into force on the twentieth day following that of its publication in
the Official Journal of the European Communities.

Article 7

(cid:1)

87/18/EEC, Art. 7

Article 8

This Directive is addressed to the Member States.

Done at Brussels, […]

For the European Parliament
The President

For the Council
The President

9

(cid:1)

1999/11/EC Art. 2

ANNEX I

THE OECD PRINCIPLES OF GOOD LABORATORY PRACTICE (GLP)

Contents

Section I

INTRODUCTION

Preface

1.

2.

Scope

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

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4.

5.

3.4. Archive facilities

3.5. Waste disposal

Apparatus, material, and reagents

Test systems

5.1. Physical/chemical

5.2. Biological

6.

Test and reference items

6.1. Receipt, handling, sampling and storage

7.

8.

6.2. Characterisation

Standard operating procedures

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

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 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» (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 Council Decision on the
mutual acceptance of data in the assessment of chemicals. [C(81)30(Final)].

11

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.

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.

2.1.

Good laboratory practice

2. Definition of terms

Good laboratory practice (GLP) 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.

2.

3.

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.

Test site means the location(s) at which a phase(s) of a study is conducted.

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.

12

4.

5.

6.

7.

8.

9.

Test site management (if appointed) means the person(s) responsible for
the phase(s) of the study, for which he is responsible, are
ensuring that
conducted according to these principles of good laboratory practice.

Sponsor means an entity which commissions, supports and/or submits a non-
clinical health and environmental safety study.

Study director means the individual responsible for the overall conduct of the
non-clinical health and environmental safety study.

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
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.

investigator(s);

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.

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.

2.

3.

4.

5.

6.

7.

Non-clinical health and environmental safety study, henceforth referred 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.

Short-term study means a study of short duration with widely used, routine
techniques.

Study plan means a document which defines the objectives and experimental
design for the conduct of the study, and includes any amendments.

Study plan amendment means an intended change to the study plan after the
study initiation date.

Study plan deviation means an unintended departure from the study plan after
the study initiation date.

Test system means any biological, chemical or physical system or a
combination thereof used in a study.

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

13

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.

9.

Specimen means any material derived from a test system for examination,
analysis, or retention.

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.

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.

2.

3.

4.

Test item means an article that is the subject of a study.

Reference item («control item») means any article used to provide a basis for
comparison with the test item.

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.

Vehicle means any agent which serves as a carrier used to mix, disperse, or
the
solubilise
administration/application to the test system.

item or

item to

reference

facilitate

test

the

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)

(b)

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;

ensure that a sufficient number of qualified personnel, appropriate
facilities, equipment, and materials are available for the timely and
proper conduct of the study;

14

(c)

(d)

(e)

(f)

(g)

(h)

(i)

(j)

(k)

(l)

ensure the maintenance of a record of the qualifications,
training,
experience and job description for each professional and technical
individual;

ensure that personnel clearly understand the functions they are to perform
and, where necessary, provide training for these functions;

ensure that appropriate and technically valid standard operating
procedures are established and followed, and approve all original and
revised standard operating procedures;

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;

for each study an individual with the appropriate
ensure that
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;

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
study.
Replacement of a principal investigator should be done according to
established procedures, and should be documented;

the delegated phase(s) of

the

ensure documented approval of the study plan by the study director;

ensure that the study director has made the approval study plan available
to the quality assurance personnel;

ensure the maintenance of a historical file of all standard operating
procedures;

ensure that an individual is identified as responsible for the management
of the archive(s);

(m)

ensure the maintenance of a master schedule;

(n)

(o)

ensure that test facility supplies meet requirements appropriate to their
use in a study;

ensure for a multisite study that clear lines of communication exist
between the study director, principal
the quality
assurance programme(s) and study personnel;

investigator(s),

(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.

15

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.

2.

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.

These responsibilities should include, but not be limited to, the following
functions. The study director should:

(a)

(b)

(c)

(d)

(e)

approve the study plan and any amendments to the study plan by dated
signature;

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;

ensure that study plans and amendments and standard operating
procedures are available to study personnel;

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;

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)

(i)

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;

ensure that after completion (including termination) of the study, the
the final report, raw data and supporting material are
study plan,
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.

16

1.4.

Study personnel's responsibilities

1.

2.

3.

4.

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.

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).

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.

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.

2.

3.

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.

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.

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)

(c)

verify that the study plan contains the information required for compliance
with these principles of good laboratory practice. This verification should be
documented;

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.

17

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)

(e)

(f)

the final reports to confirm that

inspect
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;

promptly report any inspection results in writing to management and to the
investigator(s) and the respective
study director, and to the principal
management, when applicable;

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
if applicable. This
statement would also serve to confirm that the final report reflects the raw data.

investigator(s),

3.1.

General

3. Facilities

1.

2.

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.

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.

2.

3.

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.

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.

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.

18

3.3.

Facilities for handling test and reference items

1.

2.

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.

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

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.

2.

3.

4.

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.

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.

Apparatus and materials used in a study should not interfere adversely with the test
systems.

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.

5.1.

Physical/chemical

5. Test systems

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.

19

5.2.

Biological

1.

2.

3.

4.

5.

6.

7.

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.

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.

Records of source, date of arrival, and arrival condition of test systems should
be maintained.

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.

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.

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.

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.

6.1.

Receipt, handling, sampling and storage

6. Test and reference items

1.

2.

3.

Records including test item and reference item characterisation, date of receipt,
expiry date, quantities received and used in studies should be maintained.

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.

Storage container(s) should carry identification information, expiry date, and
specific storage instructions.

20

6.2.

Characterisation

1.

2.

3.

4.

5.

6.

Each test and reference item should be appropriately identified (e.g. code,
chemical abstracts service registry number (CAS number), name, biological
parameters).

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.

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.

The stability of test and reference items under storage and test conditions
should be known for all studies.

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.

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.

2.

3.

4.

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.

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.

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.

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.

21

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)

(c)

Procedures for
receipt,
identification and care of the test system.

transfer, proper placement, characterisation,

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 GLP 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.

22

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 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 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 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.

23

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)

(e)

the dose levels and/or concentration(s), frequency, and duration of
administration/application;

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.

8.3.

Conduct of the study

1.

2.

3.

4.

5.

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.

The study should be conducted in accordance with the study plan.

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.

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.

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.

24

9.1.

General

9. Reporting of study results

1.

2.

3.

4.

5.

A final report should be prepared for each study. In the case of short-term
studies, a standardised final report accompanied by a study specific extension
may be prepared.

Reports of principal investigators or scientists involved in the study should be
signed and dated by them.

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.

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.

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
homogeneity.

the test

item including purity,

stability and

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)

(e)

name and address of the principal investigator(s) and the phase(s) of the
study delegated, if applicable;

name and address of scientists having contributed reports to the final
report.

25

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)

(d)

a presentation of the results, including calculations and determinations of
statistical significance;

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,
personnel;

training, experience and job descriptions of

(d)

records and reports of the maintenance and calibration of apparatus;

26

(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 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.

10.4.

Only personnel authorised by management should have access to the archives.
Movement of material in and out of the archives should be properly recorded.

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).

_____________

27

(cid:4)

ANNEX II

Part A
Repealed Directive and its amendment
(Article 6)

Council Directive 87/18/EEC

(OJ L 15, 17.1.1987, p.29)

Commission Directive 1999/11/EC

(OJ L 77, 23.3.1999, p. 8)

Part B
Deadlines for transposition into national law
Article 6)

Directive

87/18/EEC

1999/11/EC

Deadline for transposition

30 June 1988

30 September 1999

_____________

28

ANNEX III

CORRELATION TABLE

Directive 87/18/EEC

This Directive

Articles 1 – 5

Article 6

––––––––

––––––––

Article 7

Annex

––––––––

––––––––

Articles 1 – 5

––––––––

Article 6

Article 7

Article 8

Annex I

Annex II

Annex III

_____________

29