DEPARTMENT OF HEALTH

THE UNITED KINGDOM

GOOD LABORATORY PRACTICE

MONITORING AUTHORITY

GUIDE TO UK GLP REGULATIONS 1999

FEBRUARY 2000
CONTENTS Page No

FOREWORD 1

INTRODUCTION 1

REGULATIONS 2

1. Preamble, Citation and Commencement 2

2. Interpretation 2
3. The Good Laboratory Practice Monitoring Authority 3
4. Requirement to be a Member of the UK GLP Compliance Programme 4

Control and Monitoring of Contracted-out Work 6

5. Prospective Membership of the GLP Compliance Programme 7

6. Membership of the GLP Compliance Programme 8
7. Adherence to the Principles of GLP 10

Categories of Inspections 10
Inspection and Study Audit Procedures 11
Changes at Test Facilities 12
Inspection and Study Audit Reports 12
Warning Notices 13
Responding to Inspection and Study Audit Reports 13
GLP Compliance Statements 14

8. Complaints and Appeals 15

9. Powers of Entry 15

Role of non-GLPMA Staff in Inspections or Study Audits 16

10. Disclosure of Confidential Information 16

11. Obstruction of Authorised Persons 18
12. False Good Laboratory Practice Instruments 18
13. Offences 19
14. Defence of Due Diligence 19
15. Penalties 20
16. Fees 20
17. Revocation 20

PERFORMANCE STANDARDS 21

Consultation and Communication 22

Publication of Performance Standards 22
FOREWORD
Compliance with the principles of Good Laboratory Practice (GLP) is a legal requirement for
test facilities that undertake health and environmental safety studies, and some other testing, that
will be submitted to regulatory authorities for the purposes of risk assessment. The principles of
GLP, and the procedures implemented within the United Kingdom to monitor GLP compliance
are contained within Statutory Instrument No. 1999/3106, the Good Laboratory Practice
Regulations 1999 (the GLP Regulations).

This Guide has been produced by the UK’s GLP Monitoring Authority (GLPMA) and provides
additional information on the UK GLP compliance monitoring programme. It should be read in
conjunction with the GLP Regulations.

INTRODUCTION
The GLP Regulations and the Guide apply to any test facility which conducts, or intends to
conduct, a regulatory study. A regulatory study is a study for which the regulatory authority to
whom the data will be submitted, requires that study to be conducted in compliance with the
principles of GLP. This Guide may also be useful to those test facilities that conduct, or intend
to conduct, work that supports a regulatory study.

GLP is concerned with the organisational processes and the conditions under which certain
laboratory studies are planned, performed, monitored, recorded, archived and reported.
Adherence by test facilities to the principles of GLP ensures the proper planning of studies and
the provision of adequate means to carry them out. It facilitates the proper conduct of studies,
promotes their full and accurate reporting, and provides a means whereby the validity and
integrity of the studies can be verified. The application of GLP to regulatory studies assures the
quality of the data generated and allows its use by Government regulatory authorities in hazard
and risk assessment in particular of new substances.

The internationally accepted principles of GLP were developed by the Organisation for
Economic Co-operation and Development (OECD). These GLP principles and other
associated OECD documents were subsequently ratified by the European Commission and
transposed into EC Directives. The GLP Regulations implement these Directives within the
United Kingdom.

The UK GLP Monitoring Authority (GLPMA) has responsibility for monitoring test facilities for
compliance with the principles of GLP. The work of the GLPMA is carried out by a unit within
the Inspection and Enforcement Division of the Medicines Control Agency (MCA), which is an
executive Agency of the Department of Health (DH).

The range of test facilities monitored by the GLPMA include those involved in the health and
environmental safety testing of human and veterinary pharmaceuticals, agrochemicals, cosmetics,
food and feed additives and industrial chemicals. The test items are frequently synthetic
chemicals but may be of natural or biological origin, and in some circumstances may be living
organisms.

1
The following numbered sections correspond to the numbered Regulations in the
Statutory Instrument.

1. PREAMBLE, CITATION AND COMMENCEMENT

(1) The GLP principles originally adopted by the European Community (article 1.1 of
Council Directive 87/18/EEC) were those published by OECD in 1982 in Chapter 2 of “Good
Laboratory Practice in the Testing of Chemicals – Final report of the OECD Expert Group on
Good Laboratory Practice”. Commission Directive 90/18/EEC also endorses some OECD
recommended adaptions of the original principles that were published in OECD Environment
Monograph No. 47 and which are also set out in the Annexes to that Directive. Modified
versions of these texts (modified to take into account legislative drafting requirements) were
contained in Schedules 1 and 2 of the Good Laboratory Practice Regulations 1997.

(2) Following further consideration of key aspects of GLP by an OECD Expert Group, a
revised set of GLP principles and revised guidance for compliance monitoring procedures were
approved by OECD Council Decision C(97)186(Final). The European Commission adopted
these revised OECD documents and incorporated them into Commission Directives
1999/11/EC and 1999/12/EC in March 1999.

(3) The GLP Regulations contain all of the legislative measures necessary for the
implementation in the UK of the EC Directives on GLP. These are Council Directive
87/18/EEC, Council Directive 88/320/EEC and Commission Directive 90/18/EEC (as
subsequently amended by Commission Directives 1999/11/EC and 1999/12/EC).

(4) Section 2(2) of the European Communities Act 1972 permits any necessary regulations
to be made by designated Ministers or departments. The designation of which Ministers or
departments may exercise the power to make regulations, and details of which matters may be
so regulated, are specified in Statutory Instrument No. 1999/2788, the European Communities
(Designation) (No.3) Order 1999. This Statutory Instrument that came into force on 15th
November 1999 designates the Secretary of State as a Minister with responsibility for
“Measures relating to good laboratory practice”.

(5) The GLP Regulations came into force on 14th December 1999.

2. INTERPRETATION

(1) The definitions cited in this section of the GLP Regulations are, in most cases, identical
to the definitions contained within the original OECD texts and corresponding EC Directives.
However, there are a number of definitions that have been amended to accord with current UK
legislative drafting requirements.

2
(2) The most significant of these changes is the use of “regulatory study” to replace the term
“non-clinical health and environmental safety study”. This was necessary because the definition
of non-clinical health and environmental safety study in the revised OECD principles of GLP
includes studies which look at the properties of a test item rather than its health or environmental
safety. Because not all studies for which GLP compliance is required are concerned with
safety, the terminology had to be changed. The definition of regulatory study is given in section
4 below.

3. THE GOOD LABORATORY PRACTICE MONITORING AUTHORITY

(1) The GLP Regulations define the Good Laboratory Practice Monitoring Authority as the
body responsible for enforcing compliance with the Regulations. It consists of the Secretary of
State for Health, the National assembly for Wales, the Scottish Ministers and as respects
Northern Ireland the Department of Health, Social Services and Public Safety - either acting
alone, or any two or more of them acting jointly. They may appoint such persons as they think
necessary for the proper discharge of their functions.

(2) In practice, these functions are discharged by the GLPMA which is the management
body with responsibility for monitoring GLP compliance within the UK. In this capacity it is
responsible for administering the UK GLP compliance programme. This involves the inspection
of test facilities that are members, or prospective members, of the compliance programme, and
for conducting study audits on behalf of regulatory authorities.

(3) The GLP MA deals with all enquiries on GLP from UK and overseas regulatory
authorities. It also acts as a contact point and provides information, advice and guidance to
industry, test facilities, sponsors of studies and the public on any aspect of GLP. To this end,
the GLPMA may publish from time to time guidance on the interpretation or application of GLP
principles in particular situations or circumstances.

(4) GLP is not treated as a reserved matter under the Scotland Act 1998 or the Northern
Ireland Act 1998. Except where the functions of the GLPMA relate to matters reserved to the
Westminster Parliament (for example, international relations), its functions fall within an area of
devolved competence in respect of those countries. This is reflected in arrangements for
enforcing compliance with the GLP Regulations, arrangements which also confer on the
National Assembly for Wales identical enforcement powers to those of the Secretary of State
for Health, the Northern Ireland Assembly and the Scottish Ministers. As regards international
relations, the Head of the GLPMA represents the UK on GLP matters at EU and OECD
meetings, and the GLPMA will remain the contact point for communication with overseas
regulatory authorities on GLP matters. However, in its conduct of international relations the
GLPMA follows the relevant concordats agreed with the devolved Governments

3
(5) The GLPMA consists of a Unit Head and inspectors, appropriately qualified, with
relevant experience, and with knowledge of relevant sectors of industry. They are familiar with
the GLP Regulations and the principles of GLP, the standards necessary to comply with these
Regulations and principles, and with the regulatory requirements of authorities in the UK and
overseas.

(6) In situations where it is suspected that a criminal offence may have been committed, the
GLPMA may need to commission the assistance of other appropriate DH officials, appropriate
officials in the devolved administrations, or the police, to carry out the necessary investigations.

(7) Any investigations into possible breaches of the Regulations would usually be co-
ordinated by the GLPMA. However, if the investigation results in legal action being taken
through the courts, responsibility for this action may be assumed by the appropriate authorities
in Scotland, Wales or Northern Ireland if the alleged offence occurred there.

4. REQUIREMENT TO BE A MEMBER OR A PROSPECTIVE MEMBER OF

THE UK GLP COMPLIANCE PROGRAMME

(1) The GLP Regulations require that any test facility which conducts, or intends to
conduct, a “regulatory study” must be a member, or prospective member, of the UK GLP
compliance programme. A “regulatory study” is defined as:

A non-clinical experiment or set of experiments –

(a) in which an item is examined under laboratory conditions or in the environment in order
to obtain data on its properties or its safety (or both) with respect to human health,
animal health or the environment;

(b) the results of which are, or are intended, for submission to the appropriate regulatory
authorities; and

(c) compliance with the principles of good laboratory practice is required in respect of that
experiment or set of experiments by the appropriate regulatory authorities (whether or
not compliance with the said principles in respect of that experiment or set of
experiments is also a legislative requirement).

(2) Current European Directives do not require laboratory tests to support human clinical
trials or efficacy trials on plant protection products to be conducted according to the principles
of GLP.

4
(3) Operators of test facilities must ensure that regulatory studies are not carried out at their
premises unless they are a member or prospective member of the UK GLP compliance
programme in respect of those premises. Some operators may be members of the compliance
programme, but only in respect of defined parts of their test facility. If they subsequently intend
to carry out a regulatory study at another part of their test facility not covered by their
membership, they must apply for prospective membership of the compliance programme in
respect of that additional part of the test facility before conducting regulatory studies there.

(4) There may be circumstances when the operator of a test facility wishes to join the
compliance programme because they will be undertaking testing for which current EC Directives
do not require GLP compliance, but for which the regulatory authority to whom the data will be
submitted has stipulated that the work should be GLP compliant. If this testing constitutes a
regulatory study as defined in paragraph 4.(1) then the test facility may be admitted to the
compliance programme. They will be treated on the same basis as those test facilities
conducting regulatory studies for which GLP compliance is a legislative requirement.

(5) Not all premises generating data that may be used in a regulatory study will necessarily
need to be members of the compliance programme. Premises that are not in the UK cannot be
in the UK programme but may of course be in the programme of the country in which they are
situated. Premises involved solely in the production of background data, such as meteorological
analysis, may not need to be in the programme.

(6) It is common practice that studies, or parts of studies, may be conducted by contract
test facilities on behalf of a sponsor. In these circumstances the contract test facilities will only
need to be in the compliance programme if they undertake work that amounts to a separate
regulatory study. However, at the discretion of the GLPMA, a test facility that is conducting, or
intends to conduct, work that constitutes a discrete phase of a regulatory study may be admitted
to the compliance programme. It will be treated on the same basis as those test facilities
conducting complete regulatory studies.

(7) Whether or not the contracted-out work constitutes a regulatory study may involve
questions of fact and degree in each particular case. An example is where use is made in a
regulatory study of data generated by a specialised technique which is only available at a
particular laboratory. If the work carried out using the specialised technique is itself an
experiment that fulfils the definition of regulatory study, then the laboratory conducting that work
would need to be a member of the compliance programme.

(8) Test facilities that do not conduct, or intend to conduct, work that constitutes a
regulatory study or a discrete part thereof are not required to work in accordance with the
principles of GLP and will not therefore be admitted to membership of the UK GLP compliance
programme.

5
(9) Control and monitoring of contracted out work

(a) If the contracted-out work does not constitute a discrete regulatory study but only
part of a regulatory study, the study director is responsible for ensuring that it is
conducted in accordance with the principles of GLP. If the facility undertaking the
contracted work is itself a member of the UK GLP compliance programme, it will
not usually be necessary for representatives of the sponsoring test facility (i.e. the
test facility at which the study director is located) to carry out any specific
monitoring of the work carried out.

(b) If work that forms part of a regulatory study is contracted out to a test facility not in
the compliance programme, and it is intended to claim compliance for that part of
the study, then the sponsoring test facility must put into place quality assurance and
management mechanisms to ensure that the contracted out work is done in
accordance with GLP principles. In effect the contracted test facility will become
part of the sponsoring test facility’s GLP system for that specific part of that study.
This extension of the sponsoring test facility’s GLP system only applies to the piece
of work in question and does not apply to the contracted test facility as a whole, or
to any other work undertaken by them

(c) The management mechanisms implemented by the sponsoring test facility must be
operated to the satisfaction of the UK GLPMA. This will usually require the
contracted-out work from each separate regulatory study to be monitored by
representatives of study management and/or quality assurance from the sponsoring
test facility. If this monitoring confirms that the contracted out work was conducted
in accordance with GLP principles, then the study director may claim GLP
compliance for the complete study, including the contracted out work. Conversely,
if monitoring indicates that the work is not carried out in accordance with GLP
principles then no claim of compliance can be made for this work.

(d) When a sponsoring test facility wishes to extend their GLP system to cover
contracted out work, the GLPMA should be notified, in writing, of the test facility
to be used, the regulatory studies concerned, and the type of work to be
undertaken.

(e) If work that forms part of a regulatory study is contracted out to a test facility that is
not a member of the compliance programme, unless this work is covered by an
extension of the sponsoring test facility’s GLP system (as described in paragraphs
a, b and c above) no claim of GLP compliance can be made for this work. The
non-compliance of this work must be clearly stated in the study director statement
included in the final study report.

6
 (f) The situation is similar if an overseas test facility is contributing data towards a
regulatory study being conducted by a UK test facility. Unless the overseas facility
is a member of its own national GLP compliance programme, the UK test facility
will need to monitor the work done overseas to ensure that it is done in accordance
with GLP principles or no claim of GLP compliance can be made for this work.

(10) There may be circumstances in which the situation described in paragraph (f) above is
reversed, i.e. a test facility in the UK is contributing data towards a regulatory study being
conducted by an overseas test facility. It would not be a breach of the Regulations for the UK
test facility to conduct this work without being a member of the compliance programme
providing that the work did not constitute a discrete regulatory study as defined in paragraph
4.(1). However, if the UK test facility produced a GLP compliance statement for their work
with the intention that this statement would be submitted to a regulatory authority, this could be
a “false GLP instrument” and might constitute an offence under Regulation 12. (see section 12
for further information)

(11) In addition to the contracting out of study related work, it is also possible that other
GLP activities might be contracted out to another organisation. Such activities might include
provision of quality assurance services by a consultant: provision of computer system support:
contract archiving: facility and/or equipment maintenance. In these situations there must be
formal contracts and, if appropriate, detailed service level agreements which define the nature
and extent of services to be provided.

(12) Test facility management is responsible for ensuring that any contracted out GLP activity
is carried out in accordance with the GLP principles. When the contracted out service is
fundamental to the overall GLP compliance of the test facility, e.g. archives or computer
support, the UK GLPMA reserves the right to inspect these facilities.

5. PROSPECTIVE MEMBERSHIP OF THE UK GLP COMPLIANCE

PROGRAMME

(1) There are two categories of “membership” of the programme: full membership and
prospective membership. Prospective membership in most cases will be granted almost
automatically, once an operator has informed the GLPMA in writing of his intention to conduct
regulatory studies, or parts thereof, at particular premises. Prospective membership is granted
by the GLPMA, acknowledging in writing receipt of the operator’s application, and informing
him that he is a prospective member of the compliance programme. The GLPMA will then
carry out an initial inspection of the test facility, usually within twelve weeks of prospective
membership being granted.

7
(2) Any test facility operator who was advised by the GLPMA that they were a member,
or prospective member, of the UK GLP compliance programme before the commencement of
the 1999 GLP Regulations retain their membership status. They will remain members unless or
until they withdraw voluntarily or have their membership withdrawn in accordance with
regulations 5 and 6.

6. MEMBERSHIP OF THE UK GLP COMPLIANCE PROGRAMME

(1) If the initial inspection of a prospective member is satisfactory, the test facility operator
will be admitted to full membership of the compliance programme in respect of those premises.

(2) If the GLPMA is considering a refusal to admit the operator to the compliance
programme in respect of those premises, it is obliged, in accordance with regulations 5 and 6 –

(a) to inform the prospective member why membership is being refused

(b) to give the operator a specified period within which to make representations to the
GLPMA, and

(c) consider any representations made,

unless the GLPMA has encountered a failure to comply with GLP principles that may
precipitate a danger to animal or human health or to the environment, or the GLPMA is required
for a reason under Community law to withdraw prospective membership immediately.

(3) Once prospective membership has been withdrawn, if an operator wishes to re-apply,
he may do so, but rather than admitting them to prospective membership of the programme, the
GLPMA will normally defer any decision on membership until after a further inspection. The
GLPMA will usually make such an inspection within twelve weeks of receipt of the re-
application (unless the GLPMA considered that the re-application was not justified). If the
inspection confirms compliance with the principles of GLP, the operator will be admitted to full
membership of the programme.

(4) If circumstance arise where the GLPMA takes the view that –

(a) the operator of a test facility who is a member of the programme in respect of
particular premises is not capable of ensuring that GLP principles are adhered to at
those premises, or

8
 (b) at particular test facility premises there is a failure to adhere to GLP principles that
may precipitate a danger to human or animal health or to the environment, or

(c) the operator is not conducting, and no longer intends to conduct work that
constitutes a regulatory study or a discrete phase thereof,

then subject to the next paragraph, membership of the programme may be withdrawn in respect
of those premises.

(5) Before withdrawing membership of the programme for the reasons given in paragraph
6.(4)(a) or (c) above, the GLPMA is obliged –

(a) to inform the member that such action is being considered and explain, in writing,
the reasons for this course of action.

(b) to give the operator a specified period within which to make representations and

(c) to consider any representations which are made.

(6) If the GLPMA are considering withdrawing membership of the programme for the
reasons given in paragraph 6.(4)(b), there is no statutory requirement on the GLPMA to give
the operator prior notice and an opportunity to make representations. However, the GLPMA
will generally seek to do so, unless there are particular reasons why they need to withdraw
membership immediately, for example because of an imminent risk of harm to animal health,
human health or the environment.

(7) Where membership of the programme has been withdrawn in respect of particular
premises, operators can apply to be re-admitted to the programme in relation to those premises.

(a) Where membership has been withdrawn because the operator was not considered
capable of adhering to the principles of GLP at the test facility, the test facility can be
re-admitted to the programme when the GLPMA is again of the opinion that the
operator is capable of adhering to GLP principles at those premises.

(b) Where membership was withdrawn due to a possible danger to human or animal
health or to the environment, the test facility can be re-admitted to the programme
when that danger is no longer present.

9
 (c) Where membership has been withdrawn because the test facility, or individual
premises thereof, were not, in the opinion of the GLPMA, intending to conduct work
that constituted all or part of a regulatory study, the operator can apply to be re-
admitted to prospective membership of the programme when they demonstrate their
intention to conduct further regulatory work at those premises. Application
procedures will proceed as already described in paragraph 5(1).

7. REQUIREMENT TO ADHERE TO THE PRINCIPLES OF GLP

(1) Regulation 4 requires that any test facility which conducts, or intends to conduct, a
“regulatory study” must be a member, or prospective member, of the UK GLP compliance
programme. Regulation 7 requires any natural or legal person conducting a regulatory study at a
test facility to adhere to the principles of GLP.

(2) The purpose of the GLP compliance programme is to monitor test facilities to ensure
that they have implemented the necessary GLP procedures for the proper conduct of regulatory
studies and are capable of assuring that the resulting data are of adequate quality. The
programme encompasses test facility inspections and study audits carried out in accordance
with the internationally agreed principles of GLP.

(3) A test facility, or individual laboratory areas within a test facility, may be engaged in the
conduct of both regulatory studies (for which GLP compliance is required) and other work (for
which GLP compliance is not required). In such situations, measures must be taken to ensure
that the GLP compliance of the regulatory studies is not compromised by the conduct of the
other work. In practice, this will usually require that all work is conducted to a uniform standard
that is in accordance with the principles of GLP.

(4) Categories of inspections

Apart from the initial inspection, the inspections will fall into three categories:

(a) A system of regular, routine monitoring of test facilities, in principle on a two year
cycle. Such monitoring will involve a general inspection of the test facility and a
limited audit of ongoing or completed studies.

(b) Surveillance inspections of test facilities to monitor the effectiveness of any remedial
actions implemented as a result of serious adverse inspection findings.

10
 (c) Special test facility inspections and/or study audits at the request of regulatory
authorities in this country or overseas, e.g. prompted by a query arising from the
submission of data to that authority. Such requests will normally be for study audits
but may sometimes involve test facility inspections. It will be for the regulatory
authority concerned to identify and justify the need for any inspection or study audit
that it has requested.

(5) Inspection and study audit procedures

(a) Operators of test facilities will normally be notified in advance of any inspections or
audits which are to be carried out. However, under regulation 9 the GLPMA may,
at their discretion, conduct any inspections or audits at any reasonable hour, at short
notice or without prior notice.

(b) Study audits and directed inspections will normally take priority over the routine
inspection programme.

(c) The wide variety of test facilities and diversity of study type means that inspectors
will inevitably have to use their own judgement to assess the extent of compliance
with the principles of GLP. Inspectors will nevertheless strive for a consistent
approach in evaluating whether an adequate level of GLP compliance has been
achieved.

(d) If serious deficiencies are identified during a routine facility inspection, directed
inspection or study audit it may be necessary for the GLPMA to undertake
surveillance inspections to ensure that the test facility continues to operate in
accordance with the principles of GLP.

(e) In some instances study audits may suggest the need for a more general inspection
of the test facility. In other instances, specific requests from regulatory authorities
may be met from information derived from recently completed inspections, and
further visits to the test facility concerned may not be necessary.

(f) During test facility inspections and study audits inspectors will have discussions with
staff engaged in regulatory studies on any GLP points as they arise. A final meeting
with management and relevant test facility personnel will normally be held in order
that they may be informed of the outcome of the inspection or study audit. At this
meeting a summary of the inspector’s findings will be presented.

(g) Mention may also need to be made of work that the inspector was unable to
observe. This might include for example remote field trials stations that were not
inspected during the inspection of the parent test facility, or laboratory areas that
were not undertaking experimental work during the inspection.

11
(6) The GLPMA does not monitor: -

(a) compliance with health and safety legislation at test facilities,

(b) compliance with animal welfare legislation at test facilities,

(c) the suitability of the design of studies, or the studies’ objectives,

(d) the suitability of the test system used for the purposes of identifying any particular
hazardous property of a test item,

(e) the interpretation of the findings of the studies with respect to risks to human or
animal health or the environment.

Test facility management is, however, reminded that the interests of the GLPMA and those of
other inspectorates may overlap in some areas such as, for example, staff training, storage and
labeling of chemicals, and general hygiene.

(7) Changes at test facilities

(a) The GLPMA should be informed, in writing, of any significant changes that happen
with regards to the premises, activities or management of a test facility. Such
changes might include construction of new or extended laboratory areas, intention
to conduct additional (significantly different) study types, or major changes in key
personnel.

(b) The GLPMA will consider the possible implications of the notified changes. If
deemed appropriate, an inspector will visit the test facility in order to assess
whether GLP compliance has been affected by the changes.

(c) When there have been very significant changes to the management of a test facility,
e.g. as a result of acquisitions or mergers, it will usually be necessary for the
GLPMA to revisit the test facility

(8) Inspection and study audit reports

A full written report of the inspector’s findings will be provided to test facility management after
completion of an inspection or audit. This report will indicate the nature of any deviations from
the GLP principles or other deficiencies found at the time of inspection or audit. These may be
deviations or deficiencies that are not sufficiently serious to affect the validity of studies
emanating from the test facility, or they could be serious deviations or deficiencies that may, in
the view of the inspector, affect the validity or integrity of studies emanating from the test facility.

12
If serious deviations or deficiencies are identified and the GLPMA is considering withdrawing
prospective or full membership of the programme, the procedures described in section 6 will be
initiated.

(9) Warning notices

If the GLPMA identifies serious deviations or deficiencies which in its opinion may have affected
the validity of a regulatory study, a formal “warning notice” may be served on the operator of
the test facility. This warning notice will state the GLPMA grounds for believing that the
principles of GLP have not been adhered to, specify the measures that must be taken, require
the operator of the test facility to undertake those measures (or measures equivalent to them)
within a specified period, and outline his appeal rights under the Regulations. Failure to comply
with a warning notice that has not been withdrawn by the GLPMA or cancelled by a court is an
offence under regulation 7.

(10) Responding to inspection and study audit reports

(a) As soon as possible, and in any case no more than four weeks, a response to the
inspection or audit report should be forwarded by test facility management to the
GLPMA. This response should detail any action taken, or being taken, to rectify
the GLP deviations or deficiencies reported by the inspector.

(b) The GLPMA will consider whether, in their opinion, the proposed remedial actions
are appropriate to correct the deviations or deficiencies identified by the inspector.
The operator will be informed, in writing, whether or not the proposed remedial
actions are acceptable to the GLPMA.

(c) In the case of a routine inspection of a test facility that is a member of the
compliance programme, when the GLPMA is satisfied that all deviations or
deficiencies identified during the inspection have been corrected, a new GLP
compliance statement will be issued.

(d) When the inspection was of a prospective member, once the GLPMA is satisfied
that all deviations or deficiencies identified during the inspection have been
corrected, the operator will be admitted to full membership of the programme in
respect of specified premises and a GLP compliance statement will be issued.

(e) In the case of specific study audits the test facility will normally be invited to
comment on the audit report before it is sent to the regulatory authority that
requested the study audit. Any response to the audit report would normally be sent
to the regulatory authority which requested the study audit with a courtesy copy sent
to the GLPMA.

(f) In all cases the GLPMA reserves the right to carry out a re-inspection of a test
facility before a GLP compliance statement is either issued or renewed.

13
(11) GLP compliance statements

Inspections do not result in the formal approval of test facilities to conduct regulatory studies.
However, following a satisfactory inspection the GLPMA will normally issue a GLP compliance
statement. This states the name and address of the test facility, the date of inspection, and an
indication of the areas of expertise of that test facility.

(12) The areas of expertise that may appear on the compliance statement are:

Analytical Chemistry

Ecosystems

Environmental Fate

Environmental Toxicity

Mutagenicity

Toxicology

Phys/Chem Tests

At the discretion of the GLPMA other test categories may be included if appropriate.

(13) The statement indicates that at the time of the inspection no deviations were found of
sufficient magnitude to affect the validity of non-clinical studies performed at those facilities. The
GLP compliance statement verifies that the test facility operates in accordance with the
principles of GLP.

(14) In cases where there are only minor deviations from GLP principles which are not
sufficiently serious to affect the validity or integrity of studies emanating from the test facility, it is
considered reasonable for an inspector to report that the test facility is operating in accordance
with GLP principles. These minor deviations or deficiencies will still need to be addressed as
described in paragraph 7.(10) above.

14
8. COMPLAINTS AND APPEALS

(1) Any problems or misunderstandings between inspectors and test facility management
arising from an inspection or study audit will normally be resolved in the meeting held at the end
of the inspection or study audit. However, where problems persist and differences cannot be
reconciled, test facility management may make representations against those findings of the
inspectors that they consider unacceptable. Such representations should be made, in writing, to
the Head of the GLPMA within the four week period described in paragraph 7.(10)(a).
Appropriate steps will then be taken to achieve a mutually acceptable resolution of the problem.

(2) In the event that a test facility is not satisfied with the outcome of their representations in
relation to any matter covered in the inspection or audit report, they should refer the matter to
the Head of the Inspection & Enforcement Division of the Medicines Control Agency. In
considering any representations, the views of expert assessors drawn from outside the
Department of Health may be sought, on scientific or other matters. In seeking views, due
account will be taken of the need for confidentiality.

(3) If a test facility is still not satisfied with their treatment they may wish to refer the matter
to the Secretary of State for Health at Richmond House, 79 Whitehall, London SW1A 2NS.

(4) Where test facility management wishes to make representations about the manner in
which an inspection or audit was conducted by the inspector, the same procedures should be
followed.

(5) An operator of a test facility who is aggrieved by a decision to serve a warning notice
on him may appeal through appropriate legal channels as described in regulation 8. Essentially,
this involves an appeal to a magistrates’ court or, in Scotland, to a sheriff.

9. POWERS OF ENTRY

(1) Regulation 9 of the GLP Regulations empowers persons authorised in accordance with
regulation 3 to enter premises and to require the production of data, etc. However, such
authorised persons (usually inspectors from the GLPMA) will not normally enter any test facility
premises, or attempt to gain access to data held by a test facility without the express permission
of test facility management. Management of contract laboratories should ensure that sponsors
are aware of these provisions concerning the inspectors’ authority to require production of study
data.

15
(2) Authorised persons may also need to gain access to premises involved in a regulatory
study but in respect of which membership of the GLP compliance programme is not required.
They have the right, under the GLP Regulations, to enter any premises within the UK other than
premises used solely as a private dwelling for the purposes of enforcing compliance with the
GLP Regulations. However, as with premises of test facilities within the compliance
programme, premises will not normally be entered without the express permission of the
occupier.

(3) The GLP Regulations also contain reserve powers to obtain a warrant from a justice of
the peace authorising entry where admission has been or is likely to be refused, where an
application for admission, or the giving of notice, would defeat the object of entry, or in relation
to unoccupied premises.

(4) The role of non-GLPMA staff in inspections or study audits

(a) The GLPMA may occasionally invite (in accordance with its powers under
regulation 9 ) official representatives of other authorities to participate as observers
in an inspection or study audit. The policy of the GLPMA is that such invitations
will only normally be made with the consent of the test facility.

(b) Inspectors may also need to seek the assistance of specialists, especially when
conducting study audits. If this is done, specialists may be drawn from appropriate
Government departments, Government agencies, NHS hospitals, universities, or
private consultancy organisations.

(c) Specialists, from wherever they are drawn, will be required to give an undertaking in
writing not to use or disclose any information they may acquire in the course of an
inspection or audit. Test facilities and sponsors will be informed of the identity of
the specialists and the reasons why they are being involved.

10. DISCLOSURE OF CONFIDENTIAL INFORMATION

(1) Inspectors and other authorised persons may have access to highly confidential,
commercially valuable information whilst conducting inspections and audits. To ensure that
confidentiality is maintained:

(a) inspectors will carry warrants during inspections and study audits and can be called
upon to produce them. Other authorised persons will have appropriate means of
identification provided by the GLPMA.

16
 (b) inspectors will, if requested by the test facility, sign to confirm receipt of any
documents removed from the premises following an inspection or audit. In all cases,
where inspectors use their powers to take possession of any article, substance,
book, document, data or record, they are required to leave with a responsible
person a statement giving particulars of the whatever has been taken (regulation
9(5).

(c) all information acquired by inspectors and/or held by the GLPMA is treated
confidentially.

(2) Access to information and reports held by the GLPMA is generally restricted to the
staff of the GLPMA and its line management, and no information will be disclosed to anyone
else without proper lawful authority for doing so. There are certain authorities to whom
confidential information can lawfully be released, and some information that is not considered to
be confidential.

(3) The GLP Directives stipulate that the following information should not be considered
confidential and consequently it may be released by the GLPMA. This information is –

(a) the names of test facilities which are or have been subject to an inspection as part of
the UK GLP compliance programme;

(b) the good laboratory practice compliance status of those test facilities; and

(c) the dates upon which test facility inspections or study audits have been conducted.

(4) The GLPMA may, in the performance of its legal duties, disclose confidential
information to the European Commission, another GLP monitoring authority, a regulatory
authority, a police force or to a test facility or sponsor concerned with a particular inspection or
study audit. In addition, compliance statements and summaries of routine inspections and/or
reports of specific study audits will be made available by the GLPMA to regulatory authorities if
so requested. Copies of GLP compliance statements and audit reports will also be made
available to the facility inspected and to sponsors of the studies audited.

17
(5) In cases where the GLPMA has the proper legal authority to disclose information held
about a test facility but is not obliged to do so, the GLPMA will give due regard to the
importance of protecting sensitive commercial information which would be useful to one of the
test facility’s commercial competitors if it entered the public domain. Similar provisions will be
applied to information relating to personnel involved in the conduct of studies. The
Government’s position on disclosure of information is set out in the “Code of Practice on
Access to Government Information” by which the GLPMA is bound.

11. OBSTRUCTION OF AUTHORISED PERSONS

(1) As indicated in section 9, authorised persons have certain rights of access to test
facilities. Should access be refused, the GLPMA may inform any regulatory authority that
access has been refused and that the GLP compliance of that test facility cannot therefore be
verified.

(2) Additionally, if an authorised person is refused access to any premises of a test facility,
or is otherwise obstructed in the course of their duties, prosecution may be considered under
regulation 11.

12. FALSE GOOD LABORATORY PRACTICE INSTRUMENTS

(1) The 1999 GLP Regulations include a new offence relating to the production, possession
and submission to regulatory authorities of false good laboratory practice instruments. The most
common examples of good laboratory practice instruments are-

(a) The statement of GLP compliance issued by the UK’s GLPMA or another
national GLP monitoring authority following a test facility inspection.

(b) A letter, or other document, in which the UK’s GLPMA or another national
GLP monitoring authority confirms that certain premises of a test facility operate
in accordance with the principles of GLP, or that certain study types are
conducted in accordance with the principles of GLP.

(c) The report issued by a GLP monitoring authority as a result of a site inspection
or study audit.

(d) A statement included within a submission made to a regulatory authority in

which it is claimed that a test facility, or premises thereof, operate in compliance
with the principles of GLP.

18
 (e) A statement included within a submission made to a regulatory authority in
which it is claimed that a regulatory study, or studies, had been conducted in
accordance with the principles of GLP. This includes the study director GLP
statement that forms part of each GLP study report. (and also any Principal
Investigator statements made in respect of discrete phases of a study, if included
within the report)

(2) Making alterations or amendments to a good laboratory practice instrument which is

intended for submission to a regulatory authority would constitute production of a false
instrument.

(3) Any good laboratory practice instrument that is misleading could also be considered to
be a false instrument. For example a study director statement which claims GLP compliance for
a study that is known to be significantly flawed could constitute a false instrument. It is therefore
essential that study director statements clearly and accurately indicate any GLP deviations that
might call into question the GLP compliance of the study or a part thereof.

(4) When a test facility is undertaking a discrete phase of a study, under the control of a
principal investigator, care must be taken to ensure that the GLP compliance statement
produced by the principal investigator clearly indicates the scope of the work for which
compliance is being claimed.

13. OFFENCES

(1) The GLP Regulations describe the different offences that can be committed. Test
facility management should be aware that if an offence is committed by a body corporate or
Scottish partnership, and is proved to have been committed with the consent or connivance of,
or to be attributable to any neglect on the part of any director, manager, partner or similar, then
they, as well as the body corporate or Scottish partnership shall be deemed to be guilty of that
offence.

14. DEFENCE OF DUE DILIGENCE

(1) In any legal proceedings initiated under the GLP Regulations, it shall be a defence for
the person charged to prove that he took all reasonable precautions and exercised all due
diligence to avoid the commission of the offence.

19
15. PENALTIES

(1) If serious deviations from the principles of GLP are identified during a test facility
inspection or study audit, the GLPMA may inform appropriate regulatory authorities. The test
facility will, however, generally be informed before such action is taken.

(2) In most instances, the most effective and proportionate sanction against serious
deviations from GLP principles will simply be refusal to grant GLP compliance statements until
such time as appropriate remedial action has been taken. However, situations may arise where,
because of aggravating circumstances, the GLPMA will need to consider withdrawing
membership of the GLP compliance programme or issuing a warning notice.

(3) In the case of legal proceedings being initiated under the GLP Regulations, upon
conviction the guilty party shall be punished in accordance with the schedules described in
regulation 15. Details of the standard scale of fines may be obtained from a magistrates court.

16. FEES

(1) Test facilities that are members of the GLP compliance programme are charged fees, as
determined by the GLPMA, to cover their costs. These fees are set at levels such that they meet
that part of the expenditure of the GLPMA which is reasonably attributable to the costs of
inspecting and providing services under the GLP Regulations. Such fees have to be paid within
14 days following written notice (i.e. an invoice) from the MCA requiring payment.

17. REVOCATION

(1) The 1997 Good Laboratory Practice Regulations and associated Code of Practice are
replaced by the 1999 regulations and this Guide.

20
 PERFORMANCE STANDARDS

CONDUCT OF GLPMA BUSINESS

(1) The GLPMA aims to provide an acceptable level of service and an effective complaints
procedure. This is based on the following standards:

• All of the business conducted by the GLPMA will be carried out fairly and
impartially. The GLPMA aims to provide a service that is accurate, courteous,
efficient and positively helpful to the members of the GLP compliance programme.
Staff will identify themselves by name at all times.

• Routine test facility inspections will be undertaken, in principle, on a two yearly

cycle.

• A test facility will normally be given up to 10 working days notice of an intended

inspection.

• A test facility will be informed in writing of the results of an inspection within 15

working days of the inspection.

• The GLPMA will carry out the initial inspection of a new test facility within twelve
weeks of its being accepted as a prospective member of the GLP compliance
programme.

• All correspondence sent to the GLPMA will be acknowledged, when necessary,

within 5 working days. A reply will be sent to all enquiries within three weeks.

• Operation of a swift and effective complaints procedure.

21
 Consultation and Communication

(2) The GLPMA has established Committees through which it is able to liaise with
representatives of other regulatory authorities and industry trades associations.

(3) Any changes to the way in which the GLPMA operates will be discussed with other
UK regulatory authorities and industry by means of their representatives on the relevant
Committees.

(4) All enquiries concerning GLP should be addressed to:

GLP Monitoring Authority

Market Towers
1 Nine Elms Lane
London SW8 5NQ

Publication of Performance Standards

(5) At the end of each calendar year the GLPMA will publish the results of its performance
against the standards of service set out in this document and also views on the effectiveness of
the complaints procedure. This information will be made available via the industry
representatives on the GLP Consultative Committee.

22