Proposal for a Directive of the European Parliament and of the Council on the inspection and verification of good laboratory practice (GLP) (codified version)
Date: 2002-09-26
Institutions: European Commission
Subjects: chemical product, codification of EU law, exchange of information, health control, research body, testing

EN

COMMISSION OF THE EUROPEAN COMMUNITIES

Brussels, 26.09.2002
COM(2002) 529 final

2002/0233 (COD)

Proposal for a

DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

on the inspection and verification of good laboratory practice (GLP)

(codified version)

(presented by the Commission)

 
 
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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.

The  purpose  of  this  proposal3  is  to  undertake  the  codification  of  Council  Directive
88/320/EEC  of  7  June  1988  on  the  inspection  and  verification  of  good  laboratory
practice (GLP). 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.

The codification proposal was drawn up on the basis of a preliminary consolidation,
in all official languages, of Directive 88/320/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.

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.
Annex II, Part A of this proposal.

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2002/0233 (COD)

(cid:1) 88/320/EEC

Proposal for a

DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL

on the inspection and verification of good laboratory practice (GLP)

(Text with EEA relevance)

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,

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

(cid:1) 88/320/EEC (adapted)

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:

(1)

(2)

1

2

3

4

Council  Directive  88/320/EEC  of  7  June  1988  on  the  inspection  and  verification  of
Good  Laboratory  Practice  (GLP)3  has  been  substantially  amended  several  times4.  In
the interests of clarity and rationality the said Directive should be codified.

(cid:1) 

The application of standardised  organisational processes  and  conditions  under  which
laboratory studies are planned, performed,  recorded and reported  for the non-clinical
testing  of  chemicals  for  the  protection  of  man,  animals  and  the  environment,

(cid:1) 88/320/EEC Recital (1)

OJ C , , p. .
OJ C , , p. .
OJ L 145, 11.6.1988, p.35. Directive as last amended by Commission Directive 1999/12/EC (OJ L 77,
23.3.1999, p.22).
See Annex II, Part A.

3

                                                
hereinafter  referred  to  as  «good  laboratory  practice»  (GLP),  contributes  to  the
reassurance of Member States as to the quality of the test data generated.

(3)

(4)

(cid:1) 88/320/EEC Recital (2)
(adapted)

In  Annex  2 to its Decision of 12 May 1981  on  the  mutual  acceptance  of  data  in  the
assessment  of  chemicals,  the  council  of  the  Organisation  for  Economic  Cooperation
and  Development  (OECD)  adopted  principles  of  good  laboratory  practice  which  are
accepted  within  the  Community  and  are  specified  in  the  European  Parliament  and
Council  Directive  […]  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 substances5.

(cid:1) 88/320/EEC Recital (3)

In  the  conduct  of  tests  on  chemicals,  it  is  desirable  that  specialist  manpower  and
testing laboratory resources should not be wasted owing to the need to duplicate tests
because of differences in laboratory practices from one Member State to another. This
applies especially for animal protection which requires that the number of experiments
on  animals  be  restricted  in  accordance  with  Council  Directive  86/609/EEC  of
24 November  1986  on  the  approximation  of  laws,  regulations  and  administrative
provisions  of  the  Member  States  regarding  the  protection  of  animals  used  for
experimental and other scientific purposes6. 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.

(5)

However,  in  order  to  ensure  that  test  data  generated  by  laboratories  in  one  Member
State  are  also  recognised  by  other  Member  States,  it  is  necessary  to  provide  for  a
harmonised  system  for  study  audit  and  inspection  of  laboratories  to  ensure  that  they
are working under GLP conditions.

(cid:1) 88/320/EEC Recital (4)

(6)

Member  States  should  designate  the  authorities  responsible  for  carrying  out
monitoring on compliance with GLP.

(cid:1) 88/320/EEC Recital (5)
(adapted)

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6

OJ L , , p. .
OJ L 358, 18. 12. 1986, p. 1.

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(cid:1) 88/320/EEC Recital (6)
(adapted)

(7)

A committee, the members of which will be appointed by the Member States, would
be of assistance to the  Commission in the technical  application of this  Directive  and
would  cooperate  in  its  efforts  to  encourage  the  free  movement  of  goods  through  the
mutual recognition by  Member States of procedures  for monitoring  compliance  with
GLP. The Committee set up by 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  substances7  should  be  used  for
this purpose.

(8)

That  Committee  may  assist  the  Commission  not  only  in  the  application  of  this
Directive  but  also  in  contributing  to  the  exchange  of  information  and  experience  in
this field.

(cid:1) 88/320/EEC Recital (7)

(cid:1) 

(9)

(10)

The measures necessary for the implementation of this Directive should be adopted in
accordance  with  Council  Decision  1999/468/EC  of  28  June  1999  laying  down  the
procedures for the exercise of implementing powers conferred on the Commission8.

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:

(cid:1) 88/320/EEC, Art. 1 (adapted)

Article 1

This  Directive  shall  apply  to  the  inspection  and  verification  of  the  organisational
processes and the conditions under which laboratory studies are planned, performed,
recorded and reported for the non-clinical testing, carried out in accordance with the
rules  and  regulations,  of  all  chemicals  (e.  g.  cosmetics,  industrial  chemicals,
medicinal  products,  food  additives,  animal  feed  additives,  pesticides)  in  order  to
assess the effect of such products on man, animals and the environment.

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 184, 17.7.1999, p. 23.

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2.

3.

1.

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1.

For  the  purposes  of  this  Directive,  «good  laboratory  practice»  (GLP),  shall  mean
laboratory  practice  conducted  in  accordance  with  the  principles  set  out  in
Directive […].

This Directive does not concern the interpretation and evaluation of test results.

(cid:1) 88/320/EEC

Article 2

Using  the  procedure  laid  down  in  Article  3,  Member  States  shall  verify  the
compliance with GLP of any testing laboratory within their territory claiming to use
GLP in the conduct of tests on chemicals.

Where the provisions of paragraph 1 have been complied with, and the results of the
inspection  and  verification  are  satisfactory,  the  Member  State  in  question  may
provide endorsement of a claim by a laboratory that it and the tests that it carries out
comply  with  GLP,  using  the  formula  «Assessment  of  conformity  with  GLP
according to Directive […] on … (date)».

Article 3

Member  St  ates  shall  designate  the  authorities  responsible  for  the  inspection  of
laboratories  within  their  territories  and  for  the  audit  of  studies  carried  out  by
laboratories to assess compliance with GLP.

The authorities  referred to in paragraph 1  shall  inspect the  laboratory  and audit  the
studies in accordance with the provisions laid down in the Annex.

(cid:1) 88/320/EEC, Art. 4 (adapted)

Article 4

Each  year, Member States shall draw  up  a  report  relating  to  the  implementation  of
GLP within their territory.

This  report  shall  contain  a  list  of  laboratories  inspected,  the  date  on  which  such  inspection

was carried out and a brief summary of the conclusions of the inspections.

2.

3.

The  reports  shall  be  forwarded  to  the  Commission  each  year,  not  later  than  31
March.  The  Commission  shall  communicate  them  to  the  Committee  referred  to  in
Article 7(1). The Committee may request information in addition to those elements
mentioned in paragraph 1.

Member  States  shall  ensure  that  commercially  sensitive  and  other  confidential
information  to  which  they  gain  access  as  a  result  of  GLP  compliance  monitoring
activities  is  made  available  only  to  the  Commission,  to  national  regulatory  and

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2.

1.

2.

3.

designated authorities and to a laboratory or study sponsor directly concerned with a
particular inspection or study audit.

The names of laboratories subject to inspection by a designated authority, their GLP
compliance  status  and  the  dates  upon  which  laboratory  inspections  or  study  audits
have been conducted shall not be considered to be confidential.

(cid:1) 88/320/EEC

Article 5

Without prejudice to Article 6, the results of laboratory inspections and study audits
on  GLP  compliance  carried  out  by  a  Member  State  shall  be  binding  on  the  other
Member States.

Where a Member State considers that a laboratory within its territory claiming GLP
compliance  does  not  in  fact  comply  with  GLP  to  the  extent  that  the  integrity  or
authenticity  of  the  studies  it  performs  might  be  compromised,  it  shall  forthwith
inform the Commission. The Commission shall inform the other Member States.

(cid:1) 88/320/EEC, Art. 6 (adapted)

Article 6

Where a  Member State has sufficient  reason  to believe  that a laboratory in  another
Member State claiming GLP compliance has not carried out a test in accordance with
GLP,  it  may  request  further  information  from  that  Member  State  and  in  particular
may request a study audit, possibly in conjunction with a new inspection.

Should it not be  possible for the Member States concerned  to reach agreement,  the
Member  States  in  question  shall  immediately  inform  the  other  Member  States  and
the Commission, giving reasons for their decision.

The Commission shall examine  as  soon  as  possible  the  reasons  put  forward  by  the
Member States within the Committee referred to in Article 7(1); it shall then take the
appropriate measures in accordance with procedure referred to in Article 7(2). It may
in  this  connection  ask  for  expert  opinions  from  the  designated  authorities  in  the
Member States.

If the Commission considers that amendments to this Directive are necessary in order
to  resolve  the  matters  referred  to  in  paragraph  1,  it  shall  initiate  the  procedure
referred to in Article 7(2) with a view to adopting those amendments.

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(cid:1) 

Article 7

The  Commission  shall  be  assisted  by  the  Committee  set  up  in  Article  29  of
Directive 67/548/EEC, hereinafter "the Committee", composed of representatives of
the Member States and chaired by the representative of the Commission.

reference 

Where 
this  paragraph,  Articles  5  and  7  of
Decision 1999/468/EC  shall  apply,  having  regard  to  the  provisions  of  Article  8
thereof.

is  made 

to 

The  period  referred  to  in  Article  5(6)  of  Decision  1999/468/EC  shall  be  three
months.

The Committee shall adopt its rules of procedure.

(cid:1) 88/320/EEC, Art. 7 (adapted)

Article 8

The  Committee  referred  to  in  Article  7(1)  may  examine  any  question  which  is
referred  to  it  by  its  chairman  either  on  his  own  initiative  or  at  the  request  of  a
representative  of  a  Member  State,  concerning  the  implementation  of  this  Directive
and in particular regarding:

– 

cooperation  between  the  authorities  designated  by  the  Member  States  in
technical and administrative matters arising from the implementation of GLP,
and

– 

the exchange of information on the training of inspectors.

The  amendments  necessary  for  the  adaptation  of  the  formula  referred  to  in  Article
2(2)  and  of  Annex  I  to  take  account  of  technical  progress  shall  be  adopted  in
accordance with the procedure referred to in Article 7(2).

1.

2.

3.

4.

1.

2.

(cid:1)

Article 9

Directive 88/320/EEC,  as  amended  by  the  Directives  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 Directives 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.

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(cid:1)

Article 10

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

(cid:1) 88/320/EEC, Art. 10

Article 11

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) 1999/12/EC Art. 1

ANNEX I

The provisions for the inspection and verification of GLP which are contained in parts A and
B are those contained in Annexes I (Guides for compliance monitoring procedures for good
laboratory  practice)  and  II  (Guidance  for  the  conduct  of  test  facility  inspections  and  study
audits)  respectively  of  the  OECD  Council  Decision-Recommendation  on  compliance  with
principles of good  laboratory practice  [C(89)87(Final)] of 2 October 1989 as revised by the
OECD Council Decision amending the Annexes to the Council Decision-Recommendation on
compliance with principles of good laboratory practice of 9 March 1995 [C(95)8(Final)].

PART A

REVISED GUIDES FOR COMPLIANCE MONITORING PROCEDURES FOR GOOD
LABORATORY PRACTICE

To  facilitate  the  mutual  acceptance  of  test  data  generated  for  submission  to  Regulatory
Authorities  of  the  OECD  member  countries,  harmonisation  of  the  procedures  adopted  to
monitor  good  laboratory  practice  compliance,  as  well  as  comparability  of  their  quality  and
rigour,  are  essential.  The  aim  of  this  part  of  this  Annex  is  to  provide  detailed  practical
guidance  to  the  Member  States  on  the  structure,  mechanisms  and  procedures  they  should
laboratory  practice  compliance  monitoring
adopt  when  establishing  national  good 
programmes so that these programmes may be internationally acceptable.

It  is  recognised  that  Member  States  will  adopt  GLP  principles  and  establish  compliance
monitoring procedures according to national legal and administrative practices, and according
to priorities they give to, for example the scope of initial and subsequent coverage concerning
categories of chemicals  and  types  of  testing.  Since  Member  States  may  establish  more  than
one  Good  Laboratory  Practice  Monitoring  Authority  due  to  their  legal  framework  for
chemicals  control,  more  than  one  good  laboratory  practice  compliance  programme  may  be
established.  The  guidance  set  forth  in  the  following  paragraphs  concerns  each  of  these
Authorities and compliance programmes, as appropriate.

Definitions of terms

The  definitions  of  terms  in  the  OECD  principles  of  good  laboratory  practice  adopted  in
Article 1 of  European  Parliament  and  Council  Directive  [87/18/EEC]1 are  applicable  to  this
part of this Annex. In addition, the following definitions apply:

– 

– 

GLP  principles:  principles  of  good  laboratory  practice  that  are  consistent  with  the
OECD  principles  of  good  laboratory  practice  as  adopted  in  Article  1  of
Directive87/18/EEC],

GLP compliance monitoring: the periodic inspection of test facilities and/or auditing
of studies for the purpose of verifying adherence to GLP principles,

1

[OJ L 15, 17. 1. 1987, p. 29.]

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– 

– 

– 

– 

– 

– 

(National)  GLP  compliance  programme:  the  particular  scheme  established  by  a
Member  State  to  monitor  good  laboratory  practice  compliance  by  test  facilities
within its territories, by means of inspections and study audits,

(National)  GLP  Monitoring  Authority:  a  body  established  within  a  Member  State
with  responsibility  for  monitoring  the  good  laboratory  practice  compliance  of  test
facilities within its territories and for discharging other such functions related to good
laboratory practice as may be nationally determined. It is understood that more than
one such body may be established in a Member State,

Test  facility  inspection:  an  on-site  examination  of  the  test  facility's  procedures  and
practices  to  assess  the  degree  of  compliance  with  GLP  principles.  During
inspections, the management structures and operational procedures of the test facility
are examined, key technical personnel are interviewed, and the quality and integrity
of data generated by the facility are assessed and reported,

Study  audit:  a  comparison  of  raw  data  and  associated  records  with  the  interim  or
final report in order to determine whether the raw data have been accurately reported,
to determine whether testing was carried out in accordance with the study plan and
standard  operating  procedures,  to  obtain  additional  information  not  provided  in  the
report, and to establish whether practices were employed in the development of data
that would impair their validity,

Inspector:  a  person  who  performs  the  test  facility  inspections  and  study  audits  on
behalf of the (national) GLP Monitoring Authority,

GLP compliance status: the level of adherence of a test facility to the GLP principles
as assessed by the (national) GLP Monitoring Authority,

Regulatory  Authority:  a  national  body  with  legal  responsibility  for  aspects  of  the
control of chemicals.

Components of good laboratory practice compliance monitoring procedures

Administration

A  (national)  GLP  compliance  programme  should  be  the  responsibility  of  a  properly
constituted,  legally  identifiable  body  adequately  staffed  and  working  within  a  defined
administrative framework.

Member States should:

– 

– 

– 

ensure  that  the  (national)  GLP  Monitoring  Authority  is  directly  responsible  for  an
adequate «team»  of inspectors having the necessary technical/scientific expertise or
is ultimately responsible for such a team,

publish documents relating to the adoption of GLP principles within their territories,

publish documents providing details  of  the  (national)  GLP  compliance  programme,
including  information  on  the  legal  or  administrative  framework  within  which  the
programme  operates  and  references  to  published  acts,  normative  documents  (e.g.,
regulations,  codes  of  practice),  inspection  manuals,  guidance  notes,  periodicity  of
inspections and/or criteria for inspection schedules, etc.,

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– 

maintain records of test facilities inspected (and their GLP compliance status) and of
studies audited for both national and international purposes.

Confidentiality

(National)  GLP  Monitoring  Authorities  will  have  access  to  commercially  valuable
information  and,  on  occasion,  may  even  need  to  remove  commercially  sensitive  documents
from a test facility or refer to them in detail in their reports.

Member States should:

– 

– 

make  provision  for  the  maintenance  of  confidentiality,  not  only  by  Inspectors  but
also by any other persons who gain access to confidential information as a result of
GLP compliance monitoring activities,

ensure that, unless all commercially sensitive and confidential information has been
excised, reports of test facility inspections and study audits are made available only
to  Regulatory  Authorities  and,  where  appropriate,  to  the  test  facilities  inspected  or
concerned with study audits and/or to study sponsors.

Personnel and training

(National) GLP Monitoring Authorities should:

– 

ensure that an adequate number of inspectors is available.

The number of inspectors required will depend on:

(a)

(b)

the  number  of  test  facilities  involved  in  the  (national)  GLP  compliance
programme;

the frequency with which the GLP compliance status of the test facilities is to
be assessed;

(c)

the number and complexity of the studies undertaken by those test facilities;

(d)

the  number  of  special  inspections  or  audits  requested  by  Regulatory
Authorities,

– 

ensure that inspectors are adequately qualified and trained.

Inspectors  should  have  qualifications  and  practical  experience  in  the  range  of
scientific disciplines relevant to the testing of chemicals. (National) GLP Monitoring
Authorities should:

(a)

(b)

ensure  that  arrangements  are  made  for  the  appropriate  training  of  GLP
inspectors, having regard to their individual qualifications and experience;

encourage  consultations,  including  joint  training  activities  where  necessary,
with  the  staff  of  (national)  GLP  Monitoring  Authorities  in  other  OECD
member  countries  in  order  to  promote  international  harmonisation  in  the
interpretation  and  application  of  GLP  principles,  and  in  the  monitoring  of
compliance with such principles,

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– 

– 

ensure  that  inspectorate  personnel,  including  experts  under  contract,  have  no
financial  or  other  interests  in  the  test  facilities  inspected,  the  studies  audited  or  the
firms sponsoring such studies,

provide inspectors with a suitable means of identification (e.g., an identity card).

Inspectors may be:

– 

– 

– 

on the permanent staff of the (national) GLP Monitoring Authority,

on  the  permanent  staff  of  a  body  separate  from  the  (national)  GLP  Monitoring
Authority, or

employed  on  contract,  or  in  another  way,  by  the  (national)  GLP  Monitoring
Authority to perform test facility inspections or study audits.

In  the  latter  two  cases,  the  (national)  GLP  Monitoring  Authority  should  have  ultimate
responsibility  for  determining  the  GLP  compliance  status  of  test  facilities  and  the
quality/acceptability  of  a  study  audit,  and  for  taking  any  action  based  on  the  results  of  test
facility inspections or study audits which may be necessary.

(National) GLP compliance programmes

GLP compliance monitoring is intended to ascertain whether test facilities have implemented
GLP principles for the conduct of studies and are capable of assuring that the  resulting data
are of adequate quality. As indicated above, Member States should publish the details of their
(national) GLP compliance programmes. Such information should, inter alia:

– 

define the scope and extent of the programme.

A  (national)  GLP  compliance  programme  may  cover  only  a  limited  range  of
chemicals,  for  example,  industrial  chemicals,  pesticides,  pharmaceuticals,  etc.,  or
may  include  all  chemicals.  The  scope  of  the  monitoring  for  compliance  should  be
defined,  both  with  respect  to  the  categories  of  chemicals  and  to  the  types  of  tests
subject to it, for example, physical, chemical, toxicological and/or ecotoxicological,

– 

provide  an  indication  as  to  the  mechanism  whereby  test  facilities  enter  the
programme.

The application of GLP principles to health and environmental safety data generated
for  regulatory  purposes  may  be  mandatory.  A  mechanism  should  be  available
whereby test facilities may have their compliance with GLP principles monitored by
the appropriate (national) GLP Monitoring Authority,

– 

provide information on categories of test facility inspections/study audits.

A (national) GLP compliance programme should include:

(a)

provision for test facility inspections. These inspections include both a general
test facility inspection and a study audit of one or more on-going or completed
studies;

13

(b)

provisions  for  special  test  facility  inspections/study  audits  at  the  request  of  a
Regulatory  Authority,  for  example,  prompted  by  a  query  arising  from  the
submission of data to a Regulatory Authority,

define the powers  of inspectors  for  entry into  test facilities and their  access  to data
held  by  test  facilities  (including  specimens,  SOPs  (standard  operating  procedures)
other documentation, etc.).

While inspectors will not normally wish to enter test facilities against the will of the
facility's management, circumstances may arise  where test facility  entry  and  access
to  data  are  essential  to  protect  public  health  or  the  environment.  The  powers
available  to  the  (national)  GLP  Monitoring  Authority  in  such  cases  should  be
defined,

describe  the  test  facility  inspection  and  study  audit  procedures  for  verification  of
GLP compliance.

The  documentation  should  indicate  the  procedures  which  will  be  used  to  examine
both the organisational processes and the conditions under which studies are planned,
performed,  monitored  and  recorded.  Guidance  for  such  procedures  is  available  in
part B of this Annex,

describe  actions  that  may  be  taken  as  follow-up  test  facility  inspections  and  study
audits.

– 

– 

– 

Follow-up to test facility inspections and study audits

When  a  test  facility  inspection  or  study  audit  has  been  completed,  the  inspector  should
prepare a written report of the findings.

Member States should take action where deviations from GLP principles are found during or
after a test facility inspection or study audit. The  appropriate actions should be described in
documents from the (national) GLP Monitoring Authority.

If a test facility inspection or study audit reveals only minor deviations from GLP principles,
the facility should be required to correct such minor deviations. The inspector may need, at an
appropriate time, to return to the facility to verify that corrections have been introduced.

Where no, or where only minor deviations have been found, the (national) GLP Monitoring
Authority may:

– 

– 

issue a statement that the test facility has been inspected and found to be operating in
compliance with GLP principles. The date of the inspections and, if appropriate, the
categories of test inspected in the test facility at that time should be included. Such
statements  may  be  used  to  provide  information  to  (national)  GLP  Monitoring
Authorities in other OECD member countries,

and/or

provide  the  Regulatory  Authority  which  requested  a  study  audit  with  a  detailed
report of the findings.

14

Where  serious  deviations  are  found,  the  action  taken  by  (national)  GLP  Monitoring
Authorities  will  depend  on  the  particular  circumstances  of  each  case  and  the  legal  or
administrative  provisions  under  which  GLP  compliance  monitoring  has  been  established
within  their  countries.  Actions  which  may  be  taken  include,  but  are  not  limited  to,  the
following:

– 

– 

– 

– 

– 

issuance  of  a  statement,  giving  details  of  the  inadequacies  or  faults  found  which
might affect the validity of studies conducted in the test facility,

issuance of a recommendation to a Regulatory Authority that a study be rejected,

suspension  of  test  facility  inspections  or  study  audits  of  a  test  facility  and,  for
example  and  where  administratively  possible,  removal  of  the  test  facility  from  the
(national)  GLP  compliance  programme  or  from  any  existing  list  or  register  of  test
facilities subject to GLP test facility inspections,

requiring  that  a  statement  detailing  the  deviations  be  attached  to  specific  study
reports,

through 

action 
legal/administrative procedures so permit.

the  courts,  where  warranted  by  circumstances  and  where

Appeals procedures

Problems,  or  differences  of  opinion,  between  inspectors  and  test  facility  management  will
normally be resolved during the course of a test facility inspection or study audit. However, it
may not always be possible for agreement to be reached. A procedure should exist whereby a
test facility may make representations relating to the outcome of a test facility  inspection or
study audit for GLP compliance monitoring and/or relating to the action the GLP Monitoring
Authority proposes to take thereon.

15

PART B

REVISED GUIDANCE FOR THE CONDUCT OF TEST FACILITY INSPECTIONS AND
STUDY AUDITS

Introduction

The purpose of this part of this Annex is to provide guidance for the conduct of test facility
inspections  and  study  audits  which  would  be  mutually  acceptable  to  OECD  member
countries. It is principally concerned with test facility inspections, an activity which occupies
much  of  the  time  of  GLP  inspectors.  A  test  facility  inspection  will  usually  include  a  study
audit  or  review  as  a  part  of  the  inspection,  but  study  audits  will  also  have  to  be  conducted
from time to time at the request, for example, of a Regulatory Authority. General guidance for
the conduct of study audits will be found at the end of this Annex.

Test facility inspections are conducted to determine the degree of conformity of test facilities
and studies with GLP principles and to determine the integrity of data to assure that resulting
data  are  of  adequate  quality  for  assessment  and  decision-making  by  national  Regulatory
Authorities. They result in reports which describe the degree of adherence of a test facility to
the GLP principles. Test facility inspections should be conducted on a regular, routine basis to
establish and maintain records of the GLP compliance status of test facilities.

Further  clarification  of  many  of  the  points  in  this  part  of  this  Annex  may  be  obtained  by
referring to the OECD consensus documents on GLP (on, e.g., the role and responsibilities of
the study director).

Definitions of terms

The  definitions  of  terms  in  the  OECD  principles  of  good  laboratory  practice  adopted  in
Article 1 of Directive [87/18/EEC] and in part A of this Annex are applicable to this part of
this Annex.

Test facility inspections

Inspections for compliance with GLP principles may take place in any test facility generating
health  or  environmental  safety  data  for  regulatory  purposes.  Inspectors  may  be  required  to
audit data relating to the physical, chemical, toxicological or ecotoxicological properties of a
substance  or  preparation.  In  some  cases,  inspectors  may  need  assistance  from  experts  in
particular disciplines.

The wide diversity of facilities (in terms both of physical layout and management structure),
together  with  the  variety  of  types  of  studies  encountered  by  inspectors,  means  that  the
inspectors must  use their own judgment to assess the  degree  and  extent of  compliance  with
GLP principles. Nevertheless, inspectors should strive for a consistent approach in evaluating
whether, in the case of a particular test facility or study, an adequate level of compliance with
each GLP principle has been achieved.

In the following sections, guidance is provided on the various aspects of the testing facility,
including its personnel and procedures, which are likely to be examined by inspectors. In each
section, there is a statement of purpose, as well as an illustrative list of specific items which

16

could be considered during the course of a test facility inspection. These lists are not meant to
be comprehensive and should not be taken as such.

Inspectors  should  not  concern  themselves  with  the  scientific  design  of  the  study  or  the
interpretation  of  the  findings  of  studies  with  respect  to  risks  for  human  health  or  the
environment.  These  aspects  are  the  responsibility  of  those  Regulatory  Authorities  to  which
the data are submitted for regulatory purposes.

Test  facility  inspections  and  study  audits  inevitably  disturb  the  normal  work  in  a  facility.
Inspectors  should  therefore  carry  out  their  work  in  a  carefully  planned  way  and,  so  far  as
practicable, respect the wishes of the management of the test facility as to the timing of visits
to certain sections of the facility.

Inspectors  will,  while  conducting  test  facility  inspections  and  study  audits,  have  access  to
confidential,  commercially  valuable  information.  It  is  essential  that  they  ensure  that  such
information  is  seen  by  authorised  personnel  only.  Their  responsibilities  in  this  respect  will
have been established within their (national) GLP compliance monitoring programme.

Inspection procedures

Pre-inspection

Purpose: to familiarise the inspector with the facility which is about to be inspected in respect
of management structure, physical layout of buildings and range of studies.

Prior  to  conducting  a  test  facility  inspection  or  study  audit,  inspectors  should  familiarise
themselves  with  the  facility  which  is  to  be  visited.  Any  existing  information  on  the  facility
should be reviewed. This may include previous inspection reports, the layout of the facility,
organisation  charts,  study  reports,  protocols  and  curricula  vitae  (CVs)  of  personnel.  Such
documents would provide information on:

– 

– 

– 

the type, size and layout of the facility,

the range of studies likely to be encountered during the inspection,

the management structure of the facility.

Inspectors should note, in particular, any deficiencies from previous test facility inspections.
Where no previous test facility inspections have been conducted, a pre-inspection visit can be
made to obtain relevant information.

Test  facilities  may  be  informed  of  the  date  and  time  of  inspector's  arrival,  the  objective  of
their visit and the length of time they expect to be on the premises. This could allow the test
facility  to  ensure  that  the  appropriate  personnel  and  documentation  are  available.  In  cases
where particular documents or records are to be examined, it may be useful to identify these
to the test facility in advance of the visit so that they will be immediately available during the
test facility inspection.

Starting conference

Purpose: to inform the management and staff of the facility of the reason for the test facility
inspection  or  study  audit  that  is  about  to  take  place,  and  to  identify  the  facility  areas,
study(ies) selected for audit, documents and personnel likely to be involved.

17

The administrative and practical details of a test facility inspection or  study audit  should be
discussed  with  the  management  of  the  facility  at  the  start  of  the  visit.  At  the  starting
conference, inspectors should:

– 

– 

– 

– 

– 

– 

– 

outline the purpose and scope of the visit,

describe  the  documentation  which  will  be  required  for  the  test  facility  inspection,
such  as  lists  of  on-going  and  completed  studies,  study  plans,  standard  operating
procedures,  study  reports,  etc.  Access  to  and,  if  necessary,  arrangements  for  the
copying of relevant documents should be agreed on at this time,

clarify  or  request  information  as  to  the  management  structure  (organisation)  and
personnel of the facility,

request information as to the conduct of studies not subject to GLP principles in the
areas of the test facility where GLP studies are being conducted,

make an initial determination as to the parts of the facility to be covered during the
test facility inspection,

describe the documents and specimens that will be needed for on-going or completed
study(ies) selected for study audit,

indicate that a closing conference will be held at the completion of the inspection.

Before proceeding further with a test facility inspection, it is advisable for the inspector(s) to
establish contact with the facility's quality assurance (QA) unit.

As a general rule, when inspecting a facility, inspectors will find it helpful to be accompanied
by a member of the QA unit.

Inspectors  may  wish  to  request  that  a  room  be  set  aside  for  examination  of  documents  and
other activities.

Organisation and personnel

Purpose:  to  determine  whether  the  test  facility  has  sufficient  qualified  personnel,  staff
resources  and  support  services  for  the  variety  and  number  of  studies  undertaken;  the
organisational  structure  is  appropriate,  and  management  has  established  a  policy  regarding
training and staff health surveillance appropriate to the studies undertaken in the facility.

The management should be asked to produce certain documents, such as:

– 

– 

– 

– 

– 

floor plans,

facility management and scientific organisation charts,

CVs of personnel involved in the type(s) of studies selected for the study audit,

list(s)  of  on-going  and  completed  studies  with  information  on  the  type  of  study,
initiation/completion dates, test system, method of application of test substance and
name of study director,

staff health surveillance policies,

18

– 

– 

– 

– 

staff job descriptions and staff training programmes and records,

an index to the facility's standard operating procedures (SOPs),

specific SOPs as related to the studies or procedures being inspected or audited,

list(s)  of  the  study  directors  and  sponsors  associated  with  the  study(ies)  being
audited.

The inspector should check, in particular:

– 

– 

– 

lists  of  on-going  and  completed  studies  to  ascertain  the  level  of  work  being
undertaken by the test facility,

the  identity  and  qualifications  of  the  study  director(s),  the  head  of  the  quality
assurance unit and other personnel,

existence of SOPs for all relevant areas of testing.

Quality assurance programme

Purpose: to  determine  whether  the  mechanisms  used  to  assure  management  that  studies  are
conducted in accordance with GLP principles are adequate.

The head of the quality assurance (QA) unit should be asked to demonstrate the systems and
methods  for  QA  inspection  and  monitoring  of  studies,  and  the  system  for  recording
observations made during QA monitoring. Inspectors should check:

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

the qualifications of the head of QA, and of all QA staff,

that the QA unit functions independently from the staff involved in the studies,

how  the  QA  unit  schedules  and  conducts  inspections,  how  it  monitors  identified
critical phases  in  a  study,  and  what  resources  are  available  for  QA  inspections  and
monitoring activities,

that  where  studies  are  of  such  short  duration  that  monitoring  of  each  study  is
impracticable, arrangements exist for monitoring on a sample basis,

the extent and depth of QA monitoring during the practical phases of the study,

the extent and depth of QA monitoring of routine test facility operation,

the QA procedure for checking the final report to ensure its agreement with the raw
data,

that management receives reports from QA concerning problems likely to affect the
quality or integrity of a study,

the actions taken by QA when deviations are found,

the QA role, if any, if studies or parts of studies are done in contract laboratories,

the part played, if any, by QA in the review, revision and updating of SOPs.

19

Facilities

Purpose: to determine if the test facility, whether indoor or outdoor, is of suitable size, design
and location to meet the demands of the studies being undertaken.

The inspector should check that:

– 

– 

– 

the  design  enables  an  adequate  degree  of  separation  so  that,  for  example,  test
substances,  animals,  diets,  pathological  specimens,  etc.  of  one  study  cannot  be
confused with those of another,

environmental  control  and  monitoring  procedures  exist  and  function  adequately  in
critical  areas,  for  example,  animal  and  other  biological  test  systems  rooms,  test
substance storage areas, laboratory areas,

the general housekeeping is adequate  for the  various facilities and that  there  are,  if
necessary, pest control procedures.

Care, housing and containment of biological test systems

Purpose: to determine whether the test facility, if engaged in studies using  animals or other
biological  test  systems,  has  support  facilities  and  conditions  for  their  care,  housing  and
containment, adequate to prevent stress and other problems which could affect the test system
and hence the quality of data.

A test facility may be carrying out studies which require a diversity of animal or plant species
as well as microbial or other cellular or sub-cellular systems. The type of test systems being
used will determine the aspects relating to care, housing or containment that the inspector will
monitor. Using his judgment, the inspector will check, according to the test systems, that:

– 

– 

– 

– 

– 

– 

– 

– 

there are facilities adequate for the test systems used and for testing needs,

there  are  arrangements  to  quarantine  animals  and  plants  being  introduced  into  the
facility and that these arrangements are working satisfactorily,

there  are  arrangements  to  isolate  animals  (or  other  elements  of  a  test  system,  if
necessary) known to be, or suspected of being, diseased or carriers of disease,

there  is  adequate  monitoring  and  record-keeping  of  health,  behaviour  or  other
aspects, as appropriate to the test system,

the  equipment  for  maintaining  the  environmental  conditions  required  for  each  test
system is adequate, well maintained, and effective,

animal cages, racks, tanks and other containers, as well as accessory equipment, are
kept sufficiently clean,

analyses  to  check  environmental  conditions  and  support  systems  are  carried  out  as
required,

facilities  exist  for  removal  and  disposal  of  animal  waste  and  refuse  from  the  test
systems  and  that  these  are  operated  so  as  to  minimise  vermin  infestation,  odours,
disease hazards and environmental contamination,

20

– 

– 

storage areas are provided for animal feed or equivalent materials for all test systems;
that these areas are not used for the storage of other materials such as test substances,
pest control chemicals or disinfectants, and that they are separate from areas in which
animals are housed or other biological test systems are kept,

stored  feed  and  bedding  are  protected  from  deterioration  by  adverse  environmental
conditions, infestation or contamination.

Apparatus, materials, reagents and specimens

Purpose: to determine whether the test facility has suitably located, operational apparatus in
sufficient  quantity  and  of  adequate  capacity  to  meet  the  requirements  of  the  tests  being
conducted in the facility and that the materials, reagents and specimens are properly labelled,
used and stored.

The inspector should check that:

– 

– 

– 

– 

– 

apparatus is clean and in good working order,

records  have  been  kept  of  operation,  maintenance,  verification,  calibration  and
validation of measuring equipment and apparatus (including computerised systems),

materials  and  chemical  reagents  are  properly  labelled  and  stored  at  appropriate
temperatures and that expiry dates are not being ignored. Labels for reagents should
indicate their source, identity and concentration and/or other pertinent information,

specimens are well identified by test system, study, nature and date of collection,

apparatus and materials used do not alter to any appreciable extent the test systems.

Test systems

Purpose: to determine whether adequate procedures exist for the handling and control of the
variety  of  test  systems  required  by  the  studies  undertaken  in  the  facility,  for  example,
chemical and physical systems, cellular and microbic systems, plants or animals.

Physical and chemical systems

The inspector should check that:

– 

– 

where  required  by  study  plans,  the  stability  of  test  and  reference  substances  was
determined and that the reference substances specified in test plans were used,

in  automated  systems,  data  generated  as  graphs,  recorder  traces  or  computer  print-
outs are documented as raw data and archived.

Biological test systems

Taking  account  of  the  relevant  aspects  referred  to  above  relating  to  care,  housing  or
containment of biological test systems, the inspector should check that:

– 

test systems are as specified in study plans,

21

– 

– 

– 

– 

– 

– 

– 

– 

test  systems  are  adequately  and,  if  necessary  and  appropriate,  uniquely  identified
throughout the study, and that records exist regarding receipt of the test systems and
document fully the number of test systems received, used, replaced or discarded,

housing  or  containers  of  test  systems  are  properly  identified  with  all  the  necessary
information,

there  is  an  adequate  separation  of  studies  being  conducted  on  the  same  animal
species (or the same biological test systems) but with different substances,

there is an adequate separation of animal species (and other biological test systems)
either in space or in time,

the biological test system environment is as specified in the study plan or in SOPs for
aspects such as temperature, or light/dark cycles,

the  recording  of  the  receipt,  handling,  housing  or  containment,  care  and  health
evaluation is appropriate to the test systems,

written records are kept of examination, quarantine, morbidity, mortality, behaviour,
diagnosis and treatment of animal and plant test systems or other similar aspects as
appropriate to each biological test system,

there are provisions for the appropriate disposal of test systems at the end of tests.

Test and reference substances

Purpose: to determine whether the test facility has procedures designed (i) to ensure that the
identity, potency, quantity and composition of test and reference substances are in accordance
with their specifications, and (ii) to properly receive and store test and reference substances.

The inspector should check that:

– 

– 

– 

– 

– 

– 

there  are  written  records  on  the  receipt  (including  identification  of  the  person
responsible), and for the handling, sampling, usage and storage of tests and reference
substances,

test and reference substances containers are properly labelled,

storage conditions are appropriate to preserve the concentration, purity and stability
of the test and reference substances,

there  are  written  records  on  the  determination  of  identity,  purity,  composition,
stability,  and  for  the  prevention  of  contamination  of  test  and  reference  substances,
where applicable,

there  are  procedures  for  the  determination  of  the  homogeneity  and  stability  of
mixtures containing test and reference substances, where applicable,

containers  holding  mixtures  (or  dilutions)  of  the  test  and  reference  substances  are
labelled and that records are kept of the homogeneity and stability of their contents,
where applicable,

22

– 

– 

when the test is of longer than four weeks duration, samples from each batch of test
and reference substances have been taken for analytical purposes and that they have
been retained for an appropriate time,

procedures for mixing substances are designed to prevent errors  in identification or
cross-contamination.

Standard operating procedures

Purpose: to determine whether the test facility has written SOPs relating to all the important
aspects of its operations, considering that one of the most important management techniques
for  controlling  facility  operations  is  the  use  of  written  SOPs.  These  relate  directly  to  the
routine elements of tests conducted by the test facility.

The inspector should check that:

– 

– 

– 

– 

– 

each test facility area has immediately available relevant, authorised copies of SOPs,

procedures exist for revision and updating of SOPs,

any amendments or changes to SOPs have been authorised and dated,

historical files of SOPs are maintained,

SOPs are available for, but not necessarily limited to, the following activities:

(i)

(ii)

receipt;  determination  of  identity,  purity,  composition  and  stability;  labelling;
handling; sampling; usage; and storage of test and reference substances;

use, maintenance, cleaning, calibration and validation of measuring apparatus,
computerised systems and environmental control equipment;

(iii) preparation of reagents and dosing formulations;

(iv)

record-keeping, reporting, storage and retrieval of records and reports;

(v)

preparation and environmental control of areas containing the test systems;

(vi)

receipt,  transfer,  location,  characterisation,  identification  and  care  of  test
systems;

(vii) handling of the test systems before, during and at the termination of the study;

(viii) disposal of test systems;

(ix) use of pest control and cleaning agents;

(x)

quality assurance programme operations.

Performance of the study

Purpose:  to  verify  that  written  study  plans  exist  and  that  the  plans  and  the  conduct  of  the
study are in accordance with GLP principles.

23

The inspector should check that:

– 

– 

– 

– 

– 

– 

– 

– 

– 

– 

the study plan was signed by the study director,

any amendments to the study plan were signed and dated by the study director,

the  date  of  the  agreement  to  the  study  plan  by  the  sponsor  was  recorded  (where
applicable),

measurements,  observations  and  examinations  were  in  accordance  with  the  study
plan and relevant SOPs,

the  results  of  these  measurements,  observations  and  examinations  were  recorded
directly, promptly, accurately and legibly and were signed (or initialled) and dated,

any  changes  in  the  raw  data,  including  data  stored  in  computers,  did  not  obscure
previous  entries,  included  the  reason  for  the  change  and  identified  the  person
responsible for the change and the date it was made,

computer-generated  or  stored  data  have  been  identified  and  that  the  procedures  to
protect them against unauthorised amendments or loss are adequate,

the computerised systems used within the study are reliable, accurate and have been
validated,

any unforeseen events recorded in the raw data have been investigated and evaluated,

the results presented in the reports of the study (interim or final) are consistent and
complete and that they correctly reflect the raw data.

Reporting of study results

Purpose: to determine whether final reports are prepared in accordance with GLP principles.

When examining a final report, the inspector should check that:

– 

– 

– 

– 

– 

it is signed and dated by the study director to indicate acceptance of responsibility for
the validity of the study and confirming that the study was conducted in accordance
with GLP principles,

it  is  signed  and  dated  by  other  principal  scientists,  if  reports  from  cooperating
disciplines are included,

a quality assurance statement is included in the report and that it is signed and dated,

any amendments were made by the responsible personnel,

it lists the archive location of all samples, specimens and raw data.

Storage and retention of records

Purpose:  to  determine  whether  the  facility  has  generated  adequate  records  and  reports  and
whether adequate provision has been made for the safe storage and retention of records and
materials;

24

The inspector should check:

– 

– 

– 

– 

– 

– 

that a person has been identified as responsible for the archive,

the  archive  facilities  for  the  storage  of  study  plans,  raw  data  (including  that  from
discontinued  GLP  studies),  final  reports,  samples  and  specimens  and  records  of
education and training of personnel,

the procedures for retrieval of archived materials,

the procedures whereby access to the archives is limited to authorised personnel and
records are kept of personnel given access to raw data, slides, etc.,

that  an  inventory  is  maintained  of  materials  removed  from,  and  returned  to,  the
archives,

that records and materials are retained for the required or appropriate period of time
and are protected from loss or damage by fire, adverse environmental conditions, etc.

Study audits

Test  facility  inspections  will  generally  include,  inter  alia,  study  audits,  which  review  on-
going  or  completed  studies.  Specific  study  audits  are  also  often  requested  by  Regulatory
Authorities, and  can  be  conducted  independently  of  test  facility  inspections.  Because  of  the
wide  variation  in  the  types  of  studies  which  might  be  audited,  only  general  guidance  is
appropriate, and inspectors and others taking part in study audits will always need to exercise
judgment  as  to  the  nature  and  extent  of  their  examinations.  The  objective  should  be  to
reconstruct  the study  by comparing the  final report with the study plan, relevant  SOPs,  raw
data and other archived material.

In  some  cases,  inspectors  may  need  assistance  from  other  experts  in  order  to  conduct  an
effective study audit, for example, where there is a need to examine tissue sections under the
microscope.

When conducting a study audit, the inspector should:

– 

– 

– 

– 

– 

– 

obtain names, job descriptions and summaries of training and experience for selected
personnel engaged in the study(ies) such as the study director and principal scientists,

check  that  there  is  sufficient  staff  trained  in  relevant  areas  for  the  study(ies)
undertaken,

identify  individual  items  of  apparatus  or  special  equipment  used  in  the  study  and
examine the calibration, maintenance and service records for the equipment,

review  the  records  relating  to  the  stability  of  the  test  substances,  analyses  of  test
substance and formulations, analyses of feed, etc.,

attempt to determine, through the interview process if possible, the work assignments
of selected individuals participating in the study to ascertain if these individuals had
the time to accomplish the tasks specified in the study plan or report,

obtain copies of all documentation concerning control procedures or forming integral
parts of the study, including:

25

(i)

the study plan;

(ii)

SOPs in use at the time the study was done;

(iii)

logbooks,  laboratory  notebooks,  files,  worksheets,  print-outs  of  computer-
stored data, etc.; checking of calculations, where appropriate;

(iv)

the final report.

In studies in which animals (i.e., rodents and other mammals) are used, the inspectors should
follow  a  certain  percentage  of  individual  animals  from  their  arrival  at  the  test  facility  to
autopsy. They should pay particular attention to the records relating to:

– 

– 

– 

– 

animal body weight, food/water intake, dose formulation and administration, etc.,

clinical observations and autopsy findings,

clinical chemistry,

pathology.

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Completion of inspection or study audit

When  a  test  facility  inspection  or  study  audit  has  been  completed,  the  inspector  should  be
prepared to discuss his findings with representatives of the test facility at a closing conference
and should prepare a written report, i.e., the inspection report.

A test facility inspection of any large facility is likely to reveal a number of minor deviations
from GLP principles but, normally, these will not be sufficiently serious to affect the validity
of studies emanating from that test facility. In such cases, it is reasonable for an inspector to
report that the facility is operating in compliance with GLP principles according to the criteria
established  by  the  (national)  GLP  Monitoring  Authority.  Nevertheless,  details  of  the
inadequacies or faults detected should be provided to the test  facility and  assurances sought
from its senior management that action will be taken to remedy them.

The inspector may need  to  revisit the facility  after a period of time  to  verify  that  necessary
action has been taken.

If a serious deviation from the GLP principles is identified during a test facility inspection or
study audit which, in the opinion of the inspector, may have affected the validity of that study,
or of other studies performed at the facility, the inspector should report back to the (national)
GLP  Monitoring  Authority.  The  action  taken  by  that  Authority  and/or  the  Regulatory
Authority, as appropriate, will depend on the nature and extent of the non-compliance and the
legal and/or administrative provisions within the GLP compliance programme.

Where a study audit has been conducted at the request of a Regulatory Authority, a full report
of  the  findings  should  be  prepared  and  sent  via  the  relevant  (national)  GLP  Monitoring
Authority.

_____________

27

(cid:2)

ANNEX II

Part A
Repealed Directive and its amendments
(Article 9)

Council Directive 88/320/EEC

(OJ L 145, 11.6.1988, p.35)

Commission Directive 90/18/EEC

(OJ L 11, 13.1.1990, p.37)

Commission Directive 1999/12/EC

(OJ L 77, 23.3.1999, p.22)

Part B
Deadlines for transposition into national law
( Article 9)

Directive

Deadline for transposition

88/320/EEC

90/18/EEC

1999/12/EC

1.1.1989

1.7.1990

30.9.1999

_____________

28

ANNEX III

CORRELATION TABLE

Directive 88/320/EEC

This Directive

Articles 1 – 6 

Articles 1 – 6

––––––––

Article 7 

Article 8

Article 9

––––––––

––––––––

Article 10

Annex

––––––––

––––––––

Article 7

Article 8

––––––––

––––––––

Article 9

Article 10

Article 11

Annex I

Annex II

Annex III

_____________

29