TRIAL MASTER FILE CHECKLIST



INSTRUCTIONS

This checklist should be used as a tool to identify which essential documents should be filed in Trial Master Files (TMFs) and Investigator Site Files (ISFs), and also which documents are required for inclusion in the Sponsor file.

It also serves as a file note to identify the location of essential documents for a trial. Please complete the section at the top of page 2 to identify the location and contact for TMFs and ISFs in Tayside, and:

a. Send a copy for inclusion in the Sponsor file

b. Keep a copy of this document in your TMF

If the location of, or contact for TMF or ISF in Tayside changes, please send an updated copy of this checklist.

IMPORTANT NOTES

The essential documents listed below may not be applicable to all trials.

Where essential documents are missing a file note should be included to document the reasons for this.

Trial Master Files and Investigator Site Files may contain additional documents that are not in this list but are relevant to the management of a trial.

For some trials (e.g. single site) it may be appropriate to merge Trial Master Files and Investigator Site Files. Please make a note if this is this case.

What are ‘Essential Documents’

Essential Documents are those documents which individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced. These documents serve to demonstrate the compliance of the investigator, and sponsor with the principles of Good Clinical Practice and with all applicable regulatory requirements. Essential Documents also serve a number of other important purposes. For example: they can greatly assist in the successful management of a trial by the investigators and sponsor, and they are also the ones which are usually monitored by the sponsor and inspected by the regulatory authority(ies).

A minimum list of essential documents has been developed and is the basis of this checklist. The various documents are grouped in three sections according to the stage of the trial during which they will normally be generated: 1) before the clinical phase of the trial commences, 2) during the clinical conduct of the trial, and 3) after completion or termination of the trial. A description is given of each document, and whether it should be filed in either the ISF, TMF and/or Sponsor file. It is acceptable to combine some of the documents, provided the individual elements are readily identifiable.

TMFs and ISFs should be established at the beginning of the trial, at the investigator site and trial co-ordination site. Documents indicated for inclusion in the Sponsor file, should be provided as they become available. Any or all of the documents addressed in this guideline may be subject to, and should be available for inspection by the sponsor’s monitors and regulatory authority(ies).

Trial Master File

Location:

Contact:

Investigator Site File in Tayside

Location:

Contact:

|Essential Document |Document on File | |Trial-specific |

| | | |notes |

| |TMF |ISF |Sponsor File |Pharm. file| |

|Set-up phase (before the clinical phase of the trial commences): During this phase the following documents should be |

|generated & should be on file before recruitment starts. |

|Essential document checklist |X | |X | | |

|Database systems validation |X | | | | |

|Trial Management Systems Summary |X | |X | | |

|Including composition and charter for Project Management| | | | | |

|Group, Trial Steering Committee, Data Monitoring | | | | | |

|Committee (where applicable) | | | | | |

|List of relevant identifiers |X |X |X |X | |

|e.g. funding ref, EUDRaCT no, CTA no, REC ref, Sponsor | | | | | |

|ref, R&D ref, ISRCTN. | | | | | |

|Letter of Sponsorship |X |X |X | | |

|Investigator’s brochure |X |X |X |X | |

|or | | | | | |

|Summary Product Characteristics | | | | | |

|Signed and dated protocol, and amendments, if any, and |X |X |X |X | |

|sample case report form(s) | | | | | |

|Information to be given to trial subject, eg. sample |X |X | | | |

|PILs, sample informed consent forms, advertisement for | | | | | |

|subject recruitment | | | | | |

|Translations and back-translations of trial material |X | | | | |

|(where applicable) | | | | | |

|Financial aspects of the trial (funding |X |X |X | | |

|application/award letter/R&D costings/UoD costings) | | | | | |

|Insurance statement (where possible) |X | |X | | |

|CI/PI declaration |X |X |X | | |

| |(all) |(local) |(all) | | |

|Signed agreements between involved parties (local and |X | |X | | |

|collaborating sites; suppliers) | | | | | |

|Dated, documented approval of Research Ethics Committee |X |X |X |X* | |

|(REC), including application form, reports & | | | | | |

|correspondence, and REC composition | | | | | |

|Site specific approvals (where relevant) including |X |X |X |X* | |

|applications, approvals, and correspondence |(all) |(local) |(all) | | |

|Clinical Trial Authorisation, including application |X |X |X |X* | |

|form, approval letter and correspondence | | | | | |

|NHS R&D approval (if applicable) including application, |X |X |X |X* | |

|approval letter and correspondence |(all) |(local) |(all) | | |

|Other relevant approvals e.g. ASRAC, PIAG, GTAC. |X |X |X |X* | |

|Including application forms, approval letters and | | | | | |

|correspondence | | | | | |

|Signed/dated CV and other documents evidencing |X |X |X | | |

|qualifications of Investigators and Sub-Investigators |(all) |(local) |(all) | | |

|(local and collaborating sites) | | | | | |

|Normal values/ranges for medical/lab tests included in |X |X | | | |

|the protocol |(all) |(local) | | | |

|Medical/lab/technical procedures/tests. Certification or|X |X | | | |

|accreditation; established quality control; other |(all) |(local) | | | |

|validation | | | | | |

|Sample of labels attached to medicinal products |X |X | |X | |

|Instructions for handling of investigational products |X |X | |X | |

|and trial-related materials | | | | | |

|Many non-commercial trials use pharmacy supplies of | | | | | |

|medicinal products that have a marketing authorisation | | | | | |

|and the storage and dispensing instructions will be part| | | | | |

|of the pharmacy’s standard operating procedures for | | | | | |

|handling clinical trial materials. If this applies, | | | | | |

|provided the pharmacy SOP conforms to the applicable | | | | | |

|legislation and guidance, including retention of | | | | | |

|records, it may be noted in the TMF and ISF. | | | | | |

|Documentation and Shipping records for investigational |X |X | |X | |

|product(s) | | | | | |

|Many non-commercial trials use pharmacy supplies of | | | | | |

|medicinal products that have a marketing authorisation | | | | | |

|and so the tracking of product batches, shipping | | | | | |

|conditions and accountability will be part of the | | | | | |

|pharmacy’s standard operating procedures for clinical | | | | | |

|trials. If this applies, provided the pharmacy SOP | | | | | |

|conforms to the applicable legislation and guidance, | | | | | |

|including retention of records, this may be noted in the| | | | | |

|TMF and ISF | | | | | |

|Certificate of analysis of investigational product(s) |X |X | |X | |

|shipped; QP release | | | | | |

|Decoding procedures for blinded trials |X |X | |X** | |

|Master Randomisation List. |X | | | | |

|This may be a programme rather than a list, and may be | | | | | |

|held by the trial statistician. However, a file note | | | | | |

|should document the name and contact details of the | | | | | |

|trial statistician, and the parameters of the | | | | | |

|randomisation. | | | | | |

|Risk assessments and monitoring plan |X |X |X | | |

|Pre-trial monitoring report |X | |X | | |

|Some non-commercial trials involve investigators and | | | | | |

|sites that the sponsor judges that a pre-trial | | | | | |

|monitoring visit to be unnecessary to some or all of the| | | | | |

|sites. This should be recorded in the Sponsor and Trial | | | | | |

|Master File. Signed confirmation/agreement letters can | | | | | |

|also be used to verify that a site has suitable | | | | | |

|facilities to carry out the trial and should be kept in | | | | | |

|the Trial Master File. | | | | | |

* (previous page) Approval letter only required (not applications and correspondence)

** Pharmacy should hold a copy of the emergency code-break or be informed as to the 24-hour availability of an alternative procedure

|Essential Document |Document on File | |Trial-specific |

| | | |notes |

| |TMF |ISF |Sponsor |Pharm. file| |

| | | |file | | |

|During conduct of the trial |

|Site initiation details |X |X | | | |

|In some cases investigator training meetings are held |(all) |(local) | | | |

|prior to the trial starting, so a trial initiation visit | | | | | |

|may not be necessary. Signed confirmation/agreement | | | | | |

|letters can also be used toverify that trial procedures | | | | | |

|have been understood. Details and records of these | | | | | |

|should be included in the Trial Master File. | | | | | |

|GCP training updates; trial-specific training |X |X | | | |

| |(all) |(local) | | | |

|Monitoring reports, and revisions to monitoring plans |X |X |X | | |

| |(all) |(local) |(all) | | |

|Project Management Group, Trial Steering Committee, Data |X | | | | |

|Monitoring Committee meeting agendas, minutes and changes| | | | | |

|to composition, and/or charter. (where applicable) | | | | | |

|Investigator’s brochure updates |X |X |X | | |

|Any revision to: |X |X |X | | |

|Protocol/amendment(s) | | | | | |

|CRF | | | | | |

|Informed consent form | | | | | |

|Patient information leaflets | | | | | |

|Dated, documented approval of independent ethical |X |X |X | | |

|committee of : | | | | | |

|Protocol amendment(s) | | | | | |

|Revisions of Informed consent form and/or Patient/Parent | | | | | |

|Information Sheets | | | | | |

|Any other documents where approval required. | | | | | |

|Regulatory authorities approvals for amendments where |X |X |X | | |

|required | | | | | |

|Curriculum vitae for new investigator (s) and |X |X |X | | |

|sub-investigator(s) (local and collaborating) |(all) |(local) |(all) | | |

|Updates to normal values/ranges |X |X | | | |

| |(all) |(local) | | | |

|Updates of medical/lab/technical procedures/tests |X |X | | | |

| |(all) |(local) | | | |

|Documentation of investigational product |X |X | |X* | |

|(including shipments and new QP documents) |(all) |(local) | | | |

| Documentation to show monitoring of storage conditions | | | |X* | |

|of investigational product(s) | | | | | |

|Relevant communication other than site visits, eg. DMC, |X |X | | | |

|TSC, PMG membership, terms of reference, minutes. |(all) |(local) | | | |

|Letters inc printed emails, meeting reports, notes of | | | | | |

|telephone calls | | | | | |

|Signed informed consent forms | |X | | | |

|Notification by originating investigator to sponsor of |X |X |X | | |

|serious adverse events and related reports | | | | | |

|Notification by sponsor and/or investigator, where |X |X |X | | |

|applicable, to regulatory authorities of unexpected | | | | | |

|serious adverse drug reactions and of other safety | | | | | |

|information | | | | | |

|Notification by sponsor to investigators of safety |X |X |X | | |

|information | | | | | |

|Interim or annual reports to independent ethics |X | |X | | |

|committees (where required) | | | | | |

|Subject screening log (where required). | |X | | | |

|Delegation log |X |X | | | |

|Sample log (Record of retained body fluids/tissue | |X | | | |

|samples) (if any) | | | | | |

*Where investigator elects to store and dispense IMP, these documents must be in the TMF/ISF.

|Details |Document on File | |Trial-specific |

| | | |notes |

| |TMF |ISF |Sponsor |Pharm. file| |

| | | |file | | |

|At end of trial |

|Close-out monitoring visit report (where applicable) |X |X |X | | |

|Confirmation/agreement letters can be signed to verify |(all) |(local) |(all) | | |

|that all activities related to trial close-out are | | | | | |

|completed and that copies of essential documents are held| | | | | |

|in the appropriate files and that a site visit is not | | | | | |

|required. If this applies, it should be noted in the | | | | | |

|Sponsor and Trial Master File. | | | | | |

|Investigational product(s) accountability at site |X |X | |X* | |

| |(all) |(local) | | | |

|Documentation of investigational products destruction |X |X | |X* | |

|If this applies, provided the pharmacy SOP conforms to |(all) |(local) | | | |

|the applicable legislation and guidance, including | | | | | |

|retention of records, it may be noted in the Trial Master| | | | | |

|File. For some trials the need for reconciliation between| | | | | |

|medicinal products supplied, used and returned before | | | | | |

|destruction will require specific detailed recording if | | | | | |

|not covered by the pharmacy | | | | | |

|SOP. | | | | | |

|Final report by investigator to Independent ethics |X | |X | | |

|committee where required. | | | | | |

|Reports to funding bodies |X | |X | | |

|Records of dissemination activity (e.g. publications, |X | | | | |

|presentations, posters) | | | | | |

|Archiving arrangements |X | |X | | |

|at sites | | | | | |

|co-ordinating office | | | | | |

*Where investigator elects to store and dispense IMP, these documents must be in the TMF/ISF.

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