Safeguarding public health

Good
Laboratory
Practice
Guidance on Archiving

Medicines and Healthcare products Regulatory Agency

March 2006
CONTENTS
FOREWORD ........................................................................................................................................................2

INTRODUCTION ................................................................................................................................................2

SCOPE ..................................................................................................................................................................2

DEFINITION OF TERMS................................................................................................................................3

ROLES & RESPONSIBILITIES ..................................................................................................................4

Sponsor..................................................................................................................................................................4
Test facility management ..................................................................................................................................4
Test site management........................................................................................................................................4
Study Director ......................................................................................................................................................4
Principal Investigator ..........................................................................................................................................5
Archivist ..................................................................................................................................................................5

MANAGEMENT OF THE ARCHIVES........................................................................................................6

Archive facilities ..................................................................................................................................................6
Access to the archive ........................................................................................................................................6
Archive conditions ..............................................................................................................................................6
Archive procedures ............................................................................................................................................7
Placement of study materials into the archive............................................................................................7
Placement of non study specific materials into the archive ..................................................................7
Retrieval..................................................................................................................................................................7
Transfers ................................................................................................................................................................8

ELECTRONIC RECORDS ..............................................................................................................................9

Decision to retain records electronically......................................................................................................9
Approaches to archiving of electronic records..........................................................................................9
Maintenance and preservation of electronic records............................................................................10
Access and security ........................................................................................................................................10

RETENTION OF MATERIALS ....................................................................................................................11

Retention period................................................................................................................................................11
Business continuity and Disaster recovery ..............................................................................................12

QUALITY ASSURANCE ..............................................................................................................................12

CONTRACT ARCHIVE SERVICES ..........................................................................................................13

CLOSURE OF AN ARCHIVE......................................................................................................................14

DOCUMENTATION ........................................................................................................................................15

OTHER USEFUL DOCUMENTS/REFERENCES............................................................................16

GUIDANCE ON ARCHIVING Page 1

FOREWORD
The need for secure retention of materials from completed studies, and the retention
of supporting test facility records, is one of the fundamental requirements of the
principles of Good Laboratory Practice (GLP).

The UK Good Laboratory Practice Monitoring Authority (GLPMA) invited the

Scientific Archivists Group (SAG) and the British Association of Research Quality
Assurance (BARQA) to participate in a working group to develop guidance that could
be used to assist in the interpretation and application of the GLP principles. This
document was produced by that working group drawing upon the collective
experience of the organisations that they represented, and by reference to existing
documents on the subject. The guidance and advice contained within this document
is consistent with the requirements of the UK GLP Regulations

INTRODUCTION
The archiving of study materials and test facility records is an important part of
compliance with the principles of GLP. The maintenance of these materials is the only
means that can be used to reconstruct the study, enabling the information contained
in the final report to be verified.

The guidance contained in this document will assist in conforming to the requirements
of the United Kingdom Good Laboratory Practice Regulations (Statutory Instrument
1999 No. 3106) as amended by Statutory Instrument 2004 No. 994, “The Good
Laboratory Practice (Codification Amendments etc.) Regulations 2004” as they relate
to archiving. These regulations implement the requirements of European Directives
(2004/9/EC and 2004/10/EC) and are consistent with the OECD Principles of
Good Laboratory Practice (ENV/MC/CHEM(98)17).

SCOPE
This document is primarily intended for use by test facilities that are required to
operate in compliance with the principles of GLP, and for organisations that provide
contract archive services to such test facilities. Although aimed at GLP regulated
organisations, the guidance and advice contained within this document might be of
assistance to organisations that retain records and materials from other types of
regulatory work, for example Good Clinical Practice.

Individual organisations must ensure that they evaluate any applicable regulatory
requirements against their business needs. Certain aspects of archive construction
and operation may have implications for compliance with building regulations or
Health & Safety legislation. Guidance on these, and other such aspects, is outside
the scope of this document.

Page 2 GOOD LABORATORY PRACTICE

DEFINITION OF TERMS
Archives: The facilities and supporting resources necessary for the secure retention
and maintenance of materials accumulated by an organisation in the conduct of
regulatory studies.

Computer support staff: Designated personnel given responsibility for providing

technical support to other staff using a computerised system.

Electronic record: Information recorded in electronic form that requires a computerised

system to access or process it.

Material(s): A collective term given to all items which need to be retained for regulatory
purposes. This includes, but is not limited to; raw data, specimens, test items and non
study specific records. This includes records maintained in electronic form.

Metadata: Information associated with data that provides context and understanding,
i.e. data about data. Most commonly this is data that describes the structure, data
elements, inter-relationships and other characteristics of electronic records.

Migration: The transfer of data from a source format or system to a target format
or system.

Record: Recorded information, regardless of storage medium or characteristics, that

is evidence of an activity or an event.

Record retention schedule: A list of record types with the required storage
conditions and defined retention periods.

Refreshment: Procedures to maintain the physical viability and continued readability

of records, particularly those stored electronically. These may include copying to
fresh media or periodically running tapes to prevent sticking.

Retention period: The length of time for which materials should be kept

Storage media: The different materials on which information may be recorded.

Examples include paper, photographic film, magnetic media, microforms and
optical devices.

GUIDANCE ON ARCHIVING Page 3

ROLES & RESPONSIBILITIES
Sponsor
The sponsor is responsible for ensuring that material required to support their
regulatory studies is retained and maintained in conditions that ensure its integrity and
continued access. Storage should be in archives that meet the requirements of the
GLP principles. It is also the sponsor’s responsibility to ensure that such material is
retained for as long as it may be required by any regulatory authority.

The sponsor is directly responsible for any materials that are in their custody. The
sponsor should maintain contact with the facilities that archive its materials. This is of
particular importance when study materials have been archived at more than one
location, e.g. as a result of a multi-site study.

Test facility management

Test facility management is responsible for the provision of archive facilities. Test
facility management should appoint an individual who is responsible for the day to
day management and operation of the archives, commonly called the “Archivist”.
This appointment should be documented and authorised by management.
Consideration should be given to who would assume this responsibility in the
absence of that person.

Test facility management is responsible for ensuring that any non study specific
materials needed to support the GLP compliance status of the test facility, or of
studies conducted therein, are archived. Such records may include but are not limited
to: equipment maintenance records, personnel records, historical SOPs etc.

Removal of material from the archives should be authorised by test facility

management.

Test site management

Test site management has the same responsibilities as test facility management with
regards to archive facilities and procedures at their premises.

Study Director
The study director is responsible for ensuring that, on completion of a study, all study
specific materials are archived.

Page 4 GOOD LABORATORY PRACTICE

Principal Investigator
A principal investigator is responsible for ensuring that study specific materials for
which they were responsible have been sent to the study director, or transferred to an
agreed archive location

In this document, the term “Archivist” is used to identify the individual appointed by test facility
management to assume responsibility for day to day management of the archives.

Archivist
The archivist should be independent of any materials that are passed into their care, i.e.
they should not be responsible for archiving any study materials produced by them, as
there could be a potential conflict of interest. Where possible the archivist should be
independent of the line management responsible for the conduct of the studies.

The archivist is responsible for the day to day management of the archive facilities in
accordance with established company policies, standard operating procedures and
the principles of GLP.

In particular the archivist is responsible for:

• Controlling access to the archive

• Ensuring that orderly storage and retrieval of materials is facilitated (e.g. by means
of indexing)
• Ensuring that movement of material in and out of the archives is properly controlled
and documented.
• Ensuring that material submitted for archiving corresponds to that described in
chain of custody documentation.

In larger organisations where many studies are conducted, there may be a need for
several staff to effectively undertake archiving of the study materials produced. These
staff should work under the supervision of the designated archivist. Also, in certain
circumstances it may be necessary to designate other persons to undertake particular
archiving tasks on behalf of the archivist, e.g. to manage electronic data or to work at
remote locations.

GUIDANCE ON ARCHIVING Page 5

MANAGEMENT OF THE ARCHIVES
Archive facilities
The archive facility should be suitably designed and constructed to accommodate the
archived materials. This may be a building or a room, a fire-proof safe or lockable
cabinet. The archive facility must be secure to prevent unauthorised access to the
retained materials, e.g. by the use of locks or electronic entry systems.

Buildings or rooms should be designed to withstand the elements of local weather,

and consideration may need to be given to specific local conditions such as a risk of
flooding. Its design should protect the contents from untimely deterioration. Water
pipes in the archive areas should be avoided as there is a risk of leakage and
subsequent water damage, for example the siting of archives in basements is not ideal
due to the risk of flooding. The use of naked flames, or other open heat sources,
within or around the archives should be prohibited. It is recommended that an
automated fire detection system is installed, and management may also consider an
appropriate fire suppression system.
The facility should prevent the entry of rodent and insect pests as any infestation may
cause irretrievable damage to the archived materials. If there is a risk that pests could
gain access to the archives, a pest control programme should be implemented.

Access to the archive

Access to archive storage areas should be controlled and restricted to the archivist
and any designated archive staff. Should it be necessary for other personnel to
access the archive storage areas for any reason, they should normally be
accompanied by the archivist, or a member of the archive staff at all times. A record
of such visits should be retained; this record should include the identity of the visitor,
the identity of the attending archive staff, the reason for the visit and the date and
duration of the visit. Special arrangements may need to be made in exceptional
circumstances, e.g. “out of hours” security patrols.

Archive conditions
Storage conditions should not adversely affect the integrity of retained material.
Extremes in variation of temperature and humidity may contribute to the deterioration
of the materials being archived, so it is important to protect retained materials from
frequent fluctuations in temperature and/or humidity. The installation of systems to
control and monitor environmental conditions may be necessary.

Test facility management should define acceptable storage conditions for the different
types of retained materials. Guidance on storage conditions may be found in the
reference documents identified at the end of this document.

Page 6 GOOD LABORATORY PRACTICE

Special storage conditions may be required for particular materials, e.g. material
required to be stored frozen, refrigerated, desiccated etc., or freedom from dust or
magnetic interference in the case of electronic media. The need for special storage
conditions should be defined in relevant SOPs and the record retention schedule.

When particular storage conditions have been defined, environmental monitoring

procedures should be implemented to confirm that these conditions are being
maintained. In the case of critical materials, the need for continuous (automated)
monitoring systems, which also activate alarms in the event of defined conditions
being exceeded should be considered. There should be defined procedures for
investigating and dealing with out of specification events.

Archive procedures
Placement of study materials into the archive
The study director retains responsibility for the security of study materials until they
are accepted into the archives. During the conduct of some study types, a large
amount of materials will be produced before completion of the study and formal
archiving of the study specific materials. In these situations the provision of secure
storage facilities for study specific materials should be considered. Such facilities are
commonly termed “pre-archives”. The study director should identify all materials that
are to be archived from each study.

The study director should ensure that these materials are transferred to the archives
as soon as possible after issue of the final report.

Some study materials may be submitted to the archives by persons other than the
study director, e.g. data sent from a principal investigator, histopathology specimens
submitted by the pathologist. In these situations the study director should be
informed when these materials have been archived.

Archives staff should verify that the materials received correspond with the information
provided. There should be a documented acceptance of the study package by the
archives staff.

Placement of non study specific materials into the archive

Management should ensure that these materials, e.g. equipment records, staff training
records, organisation charts etc., are archived on a regular basis. Procedures for
archiving of these materials should be similar to those employed for study materials.

Retrieval
Materials that have been archived may, on occasion, need to be retrieved, e.g. for
regulatory inspection. The number of retrievals should be minimised; the archivist may

GUIDANCE ON ARCHIVING Page 7

provide copies of the requested information rather than releasing the raw data, or the
data may be reviewed in the presence of the archivist or designated archives staff.
Once material has been archived, test facility management assumes responsibility for
its retention. Therefore, the release of material from the archive, for whatever reason,
should be documented and approved by management.

Procedures for the removal of materials should be documented, and should include:

• The reasons for which materials may be removed from the archives (often referred
to as loans).
• The timeframe within which the removed (loaned) material should be returned to the
archive.
• How the archivist identifies any materials that have not been returned within the
specified timeframe.
• Mechanisms to ensure the return of these materials by the person to whom they had
been loaned.

On return to the archive, the materials being returned should be checked to confirm
that they correspond to the materials loaned. Management should be informed of any
discrepancies. The archivist should maintain appropriate records of all material loans
and subsequent returns.

Transfers
On occasion it may be necessary to transfer archived materials from one location to
another. The archivist transferring the material should ensure that clear confirmation
of intent is received from the owner of the archived materials (usually the sponsor)
before any transfer occurs. This should include details of the materials to be
transferred, the contact details/address of the receiving facility, and the means of
transfer between locations.
The materials to be transferred should be clearly described in appropriate chain of
custody documentation prepared by the archivist. The transportation of the material,
and associated paperwork, between the two locations should be undertaken in such
a way as to minimise the risk of loss or damage of the materials.

The recipient of the transferred materials should check that they correspond with the
associated chain of custody documentation as, once accepted, they become
responsible for ensuring that the data is maintained and preserved appropriately.
Copies of the chain of custody documentation should be retained by all parties
involved in the transfer.

Page 8 GOOD LABORATORY PRACTICE

ELECTRONIC RECORDS
Requirements for the archiving of electronic records are the same as those for other
record types, but there are some additional features, which are addressed below. It
is therefore important that management should establish a policy for the archiving of
electronic media in a secure GLP environment.

Decision to retain records electronically

The decision to retain data or records in electronic form has important implications.
The long term retention of electronic data may influence the choice of storage medium
since deterioration of storage media can lead to permanent loss of data or records.
Computer technology becomes rapidly obsolescent, and devices capable of reading
storage media in common use today may not be available in the future.

Approaches to archiving of electronic records

Intermediate storage media
Raw data is copied from a computerised system onto an intermediate storage
medium, e.g. magnetic tape, floppy disk, CD or optical disk that can be placed in a
physical archive. Archive procedures should include the consideration of additional
controls for the refreshment of these data. Consideration must be given to future
access to the data or records stored on these media. There may be a need for special
storage conditions, e.g. protection from magnetic fields.

Defined archive area on a computerised system

Data files may be moved from the production part of a computerised system to a
discrete, secure archive area on the same computer system. Data files must be
“locked” such that they can no longer be altered or deleted. Records and data
archived in this way must be under the control of a designated archivist, and be
subject to equivalent controls to those applied to other record types. “Locked” files
should only be unlocked, or returned to the production part of the system, by the
designated archivist according to documented procedures.

Dedicated electronic archive system

Raw data are migrated from the computer system that captured or manipulated them
into a separate dedicated electronic archive system. All data associated with the
reconstruction of the study needs to be migrated. This includes, but is not limited to
raw data, meta data, audit trails and associated features that allow access to the data
in the future.
The electronic archive system should be owned by the designated archivist, with
technical assistance provided by computer support staff as necessary. These staff
must follow procedures agreed with the designated archivist.

GUIDANCE ON ARCHIVING Page 9

Maintenance and preservation of electronic records
Electronic records are at risk without a preservation process to ensure that there is
access to these records in the future. Procedures should be in place to ensure that
essential information remains complete and retrievable throughout the specified
retention period. If the record medium requires processing in order to render the
retained records into a readable format, then the continued availability of appropriate
equipment should be ensured. If availability can not be ensured, the possibility of
migrating data from one medium to another should be considered.

If data migration is necessary, the process of data migration must be fully

documented, and validated, to ensure complete and accurate migration of the original
data before they are lost or destroyed.

Access and security

There should be security measures in place to ensure that only authorised personnel
can access the electronic archive system, and to enforce restrictions on access levels.
These can be both physical and logical. Physical security includes the use of
locks/keypads/cards to restrict entry to the area in which the archive system can be
accessed. Logical security is software based, e.g. passwords that are designed to limit
access to particular records. Although electronic data are under the control of the
designated archivist, computer support staff may need to help with the refreshment of
data on different storage media and with the future readability of the data.

The controls necessary to restrict access to electronic records will usually be different
from those applied to other record types. Since many electronic storage media can
be re-used (e.g. overwritten) controls should be implemented to ensure that records
can not be altered or deleted without appropriate authorisation. If records can be
altered or deleted there must be a full audit trail of all such changes.

Page 10 GOOD LABORATORY PRACTICE

RETENTION OF MATERIALS
Retention period
Materials should be retained for the period(s) specified in other applicable legislation
or guidance. If specific retention periods are not defined, then test facility management
should draw up a record retention schedule for the different types of retained materials.
This schedule should define each type of material, the storage conditions and periods
of storage. The retention period set should take account of any legal, regulatory,
operational, historical or fiscal requirements that apply to the organisation.

The retention period is usually a fixed period from the time that the record was
created, but may be a fixed period following a defined event, e.g. “after completion of
the study”; “after termination of employment”.
When determining appropriate retention periods, the following factors should be
considered:
• The possible risks to the organisation should the material not be available for
examination at any time in the future. Study data and supporting records should be
retained for as long as there is a likelihood that they will need to be referred to for
regulatory purposes.

• Supporting material (e.g. staff training records, equipment calibration records etc.)
that would be required to confirm the validity of study material should be kept for as
long as the study material that they support.

• Specimens and samples need not be retained, for regulatory purposes, for periods
of time beyond which no useful information could be derived from them, e.g.
retention of test materials that are known to have only limited stability.

• The possibility of migrating data from one medium to another could be considered,
e.g. bulky paper data could be copied onto microfilm or scanned into electronic
form etc. If data is migrated from one medium to another, the potential problems of
future readability will need to be considered.

GUIDANCE ON ARCHIVING Page 11

Business continuity and Disaster recovery
It is important that test facilities have clear documented procedures that detail the
steps to be taken to minimise damage to archived materials caused by significant
adverse events. The types of event to be considered in the plan should be
determined by an assessment of the risks that the archive may be exposed to. These
are likely to be dependant on the archive’s location and environment. Risks to be
considered should include fire, flood, pest infestation, and structural damage due to,
e.g. subsidence and forced entry of the archive by unauthorised persons.
The plan should cover recovery and/or restoration of lost or damaged materials, and
should re-establish the security of damaged and undamaged material. It should
include useful contacts, the whereabouts of necessary equipment, and the records
that should be made. It should take into account possible roles of the emergency
services, define who may access the archive in an emergency, and identify that access
to the archive by employees will be denied while there is a risk to their health and safety.
It may be useful to establish contacts with appropriate specialist organisations that can
provide a service to recover and/or restore damaged archived materials.

It may be appropriate for business continuity plans to be tested periodically in a

simulation exercise.

QUALITY ASSURANCE
The quality assurance programme for the test facility should include the archive
facilities and their operation; routine QA inspections of the archive facility and its
operation must be conducted.

It is not uncommon for management of the archive function to rest with the QA
manager, and QA staff may be designated as archivists. In these situations there is a
possible conflict of interest. This can be avoided by the use of an external QA
consultant or the use of other suitably trained/experienced staff from outside of the
archives/QA department. Alternatively, procedures could be established that allow
non-archivist QA officers to perform the inspections/audits and report any findings
directly to management, thus by-passing the usual reporting lines that could give rise
to a conflict of interest.

Page 12 GOOD LABORATORY PRACTICE

CONTRACT ARCHIVE SERVICES
The GLP principles require that a test facility has an archive to provide secure storage
of data, records and specimens. This will usually consist of archive facilities within the
test facility itself, but the use of contract archive facilities is not precluded (refer to
guidance contained within the “Guide to UK GLP Regulations”). If contract archive
facilities are used, the general guidance contained within this document should apply,
and the following should also be considered.

Service Level Agreements

There should be a formal, documented, agreement between the contract archive and
test facility/test site management that details the level and conditions of service to be
provided. This agreement should define the location of the archive facilities that will
be used, and cover the transportation of material to the archive (including any
necessary environmental conditions to be maintained during transport), chain of
custody, access to stored material by the contract archive, storage conditions, period
of storage, method of retrieval/access and method of return/disposal. The contract
archive organisation should follow relevant SOPs, either its own, or those provided by
test facility management. This should be specified in the agreement.

Access arrangements
Procedures should define how, and when, stored material can be accessed by
representatives of the test facility. Any such access should be documented.

Conditions of storage
The conditions of storage within the contract archive facility should be the same as
those expected of a test facility archive which is operated in compliance with the GLP
principles. This will include the management appointment of an archivist, written and
approved SOPs describing their activities and the provision of suitable storage areas
to prevent deterioration or loss of stored materials.

Audits
Representatives of Quality Assurance from the test facility/study sponsor must
inspect the contract archive facility periodically to ensure that the conditions of the
service level agreement are being met. The systems and procedures operated by the
contract archive facility should comply with their own SOPs, the GLP principles and
any other applicable regulatory requirement.

GUIDANCE ON ARCHIVING Page 13

CLOSURE OF AN ARCHIVE
If a test facility closes down, the fate of any archived materials needs to be
determined. Materials should be retained in secure (GLP standard) archives in case
the records were to be the subject of a formal regulatory study audit in the future.
When the test facility that is closing down is part of a larger organisation, there is the
possibility that retained materials could be transferred to other (GLP standard)
archives within that organisation. Any such transfer of materials should be carried out
under closely controlled conditions and appropriate records maintained.

If the test facility that is closing down is a contract research organisation, in the first
instance they should contact the sponsors of the work that they have undertaken and
ask for advice on the disposition of any retained materials. Possible scenarios are:

• The sponsor may request that study materials are returned to them. To ensure the
validity of these study data it might also be necessary for the sponsor to obtain
copies of relevant non-study specific material such as equipment calibration
records etc.

• The sponsor may request that their data be transferred to another storage
location specified by them. Again, it might be necessary for them to obtain
copies of relevant non-study specific material that would be necessary to support
the study data.

• The sponsor may instruct the test facility to destroy some, or all of their data.

In each case, the sponsor should ensure that there are complete and accurate
records of the final disposition of all data, records and specimens from GLP compliant
studies. Consideration should also be given to the fate of non study specific
supporting records.

In any circumstances, test facilities in the United Kingdom may contact the GLPMA
for advice and guidance.

Page 14 GOOD LABORATORY PRACTICE

DOCUMENTATION
Management approved SOPs that describe archiving procedures should be
maintained.

SOPs will include, but not necessarily be limited to, the following:

• Definition and description of the facilities which constitute the archive.

• The conditions under which material is stored and any monitoring of those
conditions.
• Procedures to ensure the integrity of the archive storage facilities and material
stored. This might include pest control, environmental monitoring and checks on
the conditions of material stored.
• Procedures for the receipt and checking of material to be archived.
• Maintenance of archived material, including the migration of electronic data.
• Indexing of archived material to ensure timely retrieval.
• Retrieval of archived material for temporary loan (including permissible loan
periods), permanent transfer, authorised destruction or further examination.
• Return of loaned materials into the archive.
• Security of the archive facility and the material retained, including access controls.

Other documentation to be retained will include:

• Records of appointment of the archivist and archives staff.
• The record retention schedule.
• The business continuity plan.
• Records of materials accepted into the archives.
• Third party agreements (where applicable).

GUIDANCE ON ARCHIVING Page 15

OTHER USEFUL DOCUMENTS/REFERENCES
References

Guide to UK GLP Regulations 1999, MHRA

GAMP 4 Recommended Environmental Conditions for Storing Various Recording Media

Recommended Environmental Conditions for Storing Various Recording Media —

www.michigan.gov

European Commission Detailed Guidelines on the Trial Master file and Archiving
ENTR/F/2 D2002

Consultative Committee on Space Data Systems — The Blue Book (CCSDS

650.0-B-1) the Reference Model for an Open Archival Information System (OAIS)
http://ssdoo.gsfc.nasa.gov/nost/isoas/ref_model.html. This Recommendation has
been adopted as ISO14721:2002.

Consultative Committee on Space Data Systems — The Red Book

(CCSDS 651.0-R-1)
Guidance to Industry – Archiving Submissions in Electronic Format — NDAs
www.fda.gov/cder/guidance/index.htm

FDA CFR 21 Part 11

BS 5454:2000 Storage and exhibition of archival documents, and DISC PD

0024:2001 guide to its interpretation.

ISO 11799: 2003(E) Information and documentation — Document storage

requirements for archive and library materials.

Good Practice and Compliance for Electronic Records and Signatures.

Part 1 Good Electronic Records Management (GERM). ISPE and PDA July 2002

BS ISO 15489-1:2001, Information and documentation Records management

(Part 1 General, Part 2 Guidelines)

There is a series of OECD guidance documents on specific aspects of Good Laboratory

Practice. These documents may include additional specific requirements relating to archive
procedures. These documents may be obtained from OECD, Paris.

Page 16 GOOD LABORATORY PRACTICE

Medicines and Healthcare products Regulatory Agency
Market Towers 1 Nine Elms Lane London SW8 5NQ
T 020 7084 2000 F 020 7084 2353 www.mhra.gov.uk