Standard Operating Procedure
SP04-H
Investigator Site File
This English translation is based on a German document which has been developed in line with the
harmonisation procedure for the creation of Standard Operating Procedures for Clinical Trials (SOP) as
described in SOP "GE01". The German version has been adopted by many German Research Institutions
which focus on Investigator Initiated Trials (IIT), in particular the member organisations of KKSN (www.kksnetzwerk.de) and TMF (www.tmf-ev.de).
This English translation is meant for facilitating the creation and adoption of Standard Operating Procedures in
multinational clinical trials. Please note:
 Not every German SOP document was eligible for translation, thus the set of English translations is NOT
COMPLETE.
 Updating of English translations does not follow the same update cycle as for the German originals, so some
English versions might be OUTDATED compared to the German versions. The respective files are flagged
with an "outdated" suffix in their file name. Surely these versions are still useful and therefore downloadable
on TMF website.
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guarantee with regard to the accuracy of content. Reproduction and transmission are solely
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agreed with TMF. For reasons of quality assurance and transparency with regard to
dissemination and use of the TMF results any further dissemination will solely take place via the TMF website or
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This work has been developed as work material, which is why changes may be made to printouts or renamed
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The writing and revision of the SOPs and
their appendices was funded by:
Standard Operating Procedure
SP04-H
Investigator Site File
Version:
V03
Translation of:
Investigator Site File (ISF), SP04-H V03
Valid from:
December 14, 2011
of:
September 22, 2008
Author:
Edith Belz
Date
Author signature
Date
Translator signature
Translator:
Dr. Bärbel Kästner
Target group:
Appendices:
SP04-H-A1
SP04-H-A2
SP04-H-A3
Sample: Notice of Missing Information
Sample: ISF Table of Contents
Sample: ISF Checklist
Generation of the SOP by the Quality Management Group of the
KKS-Network under collaboration with cooperating CompetenceNetworks
SP04-H
Investigator Site File
V03
Contents
Page
4
4
4
4
4
4
5
5
5
6
6
1
2
3
Objective
Background
Processes
3.1 Compilation of the ISF
3.1.1 When is the ISF compiled?
3.1.2 Content of the ISF
3.1.3 Check and Release of ISF
3.1.4 Provision of ISF
3.2 Maintenance of the ISF
4
References
5
Changes from last version
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Objective
The objective of this SOP is to specify quality standards for the KKS network for the
consistent compilation of Investigator Site Files (ISFs) and the consistent, proper and
complete filing of trial-relevant documentation in the ISF.
2
Background
A range of documents are required for the planning, conduct and evaluation of a clinical trial.
These documents serve to document the trial and enable the quality of the trial and the data
collected to be evaluated. These documents also serve to document that ICH-GCP has been
adhered to and that all legal requirements have been fulfilled (EU Guideline 2005/28/EC,
Section 4, Article 16, and ICH-GCP Guideline E6, Section 8).
The availability of these documents at the investigational site enables the trial to be
conducted properly. The ISF contains all documents which, during the course of the trial, are
supplied to, prepared by and completed at the trial site.
This documentation may be audited by independent auditors and inspected by the
competent authorities.
The trial sites involved are responsible for ensuring that the documents are available and,
where applicable, for the updating and completeness of the trial documentation, and for the
local archiving of the file.
3
Processes
The KKS can assume responsibilities on behalf of the sponsor for clinical trial Director KKS
activities provided this is agreed in advance (e.g. by contract or
authorisation). The sponsor may contract the KKS to compile the ISF.
The management of the KKS may delegate the compilation of the ISF to a
member of the KKS staff.
3.1
Compilation of the ISF
3.1.1 When is the ISF compiled?

The ISF is compiled before the clinical trial starts.

Before it is provided to the trial site, the completeness and up-todateness of the ISF is checked again.
Project
manager
3.1.2 Content of the ISF
The documents required in the ISF and documents that must be filed
elsewhere must be defined before compiling the ISF. This must be done in
agreement with the sponsor.
Project
manager
The documents that are generally archived in the ISF are given in the Sample
Checklist in Appendix 3 of this SOP. The column headers in the checklist can
be used to indicate whether a document is required for the clinical trial or not.
An ISF is prepared for every trial site. If necessary, it can consist of several
folders.
All ISFs have a consistent structure and consistent trial-specific labelling:
 Table of contents (see Appendix 2).
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 Spine label.
 Dividers.
The following information appear on the spine label of the ISF folders:
Section for local specification
 Study title.
 Placeholders for trial site, site number, investigator’s name.
 KKS logo.
 Brief trial ID (sponsor and/or KKS).
 Trial ID (sponsor, internal . . .).
 EudraCT number (for trials according to AMG).
 Numbering of the ISF section (folder number).
 Description of ISF section.
 Further information depending on the agreement with the sponsor.
The table of contents of the ISF is prepared based on local conditions of the
KKS, on the sample table of contents given in Appendix 2, and, if required, on
information from Appendix 3.
The trial-specific table of contents and the checklist are archived in the TMF.
3.1.3 Check and Release of ISF
Section for local specification
In multi-centre trials the first ISF is considered as sample ISF. The sample
ISF, the completed checklist ISF (Appendix 3) as well as the table of content
must be checked by the responsible person (specified by KKS).
Project
manager,
Monitor
The release is documented by the responsible person by a note “release”,
initials and date directly on the checklist ISF and on the table of content of the
sample ISF. By doing this the creation of the chapters resp. sub-chapters in
the table of content is released. A copy of the checklist and the signed table
of content must be filed in the TMF. The ISFs for other trial sites should be
compiled not before the release of the sample ISF.
3.1.4



Provision of ISF
The ISF is generally supplied to the trial site at the initiation visit – the
trial site confirms receipt with the signature of the person responsible.
The ISF may also be distributed at an investigators’ meeting or sent by
post. In both cases, receipt must be confirmed in writing.
Documentation of dispatch and receipt is filed in the TMF.
Project
manager
3.2 Maintenance of the ISF
The trial team at the trial site is responsible for maintaining, storage and, if Monitor, data
necessary, updating the ISF, and the completeness/up-to-dateness and management
proper storage of the ISF is checked by the monitor based on the contractual
agreement.
Storage
 No third-party access. Trial staff and auditors and inspectors
always have access.
Correspondence
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 Correspondence is always filed in chronological order
 Documents should always be filed according to subject matter, if
possible
Electronic documents
 Section for local specificationGenerally, electronic documents are
printed out and filed in the ISF in paper form. When using an
electronic CRF, a printed sample CRF should exist, e.g.
Screenshots.
 Electronic CRFs should be printed once as sample by the data
management; this printed sample CRF should be filed. At the end
of the trial the data management should provide the trial site with a
CD/DVD of all electronic CRF data for filing in the ISF.
Removal of documents for a limited period
 As a general rule, documents must always stay in the ISF and may
not be removed.
 If a document has to be removed for a limited time or is filed
outside of the ISF (e.g. contract), a notice of removal using the
sample ‘Notice of missing information’ (Appendix 1) must be
placed at the appropriate point in the file. When the document is
returned, the notice is removed and destroyed.
 The investigators should receive a template for the ‘Notice of
missing information’ (see SP04-H-A1).
Archiving
 The ISF is generally archived at the trial site. At the trial close-out
visit, the monitor must inform the investigator of the required
archiving period and request that the investigator contact the KKS
or sponsor before destruction.
For further information, see the SOP “Archiving”.
4
-
References
ICH Topic E6, Note for Guidance on Good Clinical
(CPMP/ICH/135/95), 1997
EU Commission Guideline 2005/28/EC, Section 4, Article 16
Practice
(GCP)
Cross-references to existing SOPs
SOP-ID
GE02-H
5
Titel
Archiving
Changes from last version
Section
Cover page
1. Objective
3. Processes
3. Processes
3. Processes
3. Processes
Appendix 1
Subsection
Target group
1. sentence
3.1.2
3.1.2
3.1.3
3.2
Description of changes
“All Coordination Centres for Clinical Trials” deleted
“the KKS” replaced by “the KKS network”
“Attachment 1” was replaced by “Appendix 1”
Section for local specification
Section for local specification
Section electronic documents refined; section for local
specification
Revised, see changes listed on the cover page
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Appendix 2
Appendix 3
4. References
Investigator Site File
V03
Revised, see changes listed on the cover page
Revised, see changes listed on the cover page
Headline/list “Cross-references to existing SOPs” added
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