[Eldin Rammell]

Hi Debra,

In general, the proposed Diversity Plans will not be trial-specific but will rather be plans across a product development program. On this basis, I suggest they would not be expected to be filed in the Trial Master File.

Were a trial-specific Diversity Plan to be created, my suggestion would be to file under 01.01.02 Trial Management Plan on the basis that its purpose is aligned with the definition/purpose of this artifact

or 03.01.01 Regulatory Submission on the basis that it is a trial-related document that is submitted to a regulatory agency (filed to the IND).

The draft guidance seems to suggest that its use will be recommended rather than mandatory, though it does sound as though the FDA are being pressurized to mandate its use.

Any thoughts from others?

Kind regards,
Eldin.

[Eldin Rammell]

Hi Sarah,

Remember that the TMF is a trial-specific repository. So whilst the records you mention need to be retained and could be reviewed in an inspection, they would not be expected in the TMF. Most companies have a separate system in which they maintain validation records and records of system management, such as user access requests, change requests etc.

Kind regards,
Eldin.

[Eldin Rammell]

Hi Anke

In general, each artifact in the Reference Model also includes any associated approvals.

Eldin.

[Eldin Rammell]

Hi Patricia,

I cannot provide figures but I would warn against under-estimating how much time this will take. I have experience of developing SharePoint for another regulated document management system in a previous role and the effort was huge (development cost in excess of £50k 10 years ago).

I suggest taking a look at the GAMP5 requirements, if you’ve not done already, to identify what you would need to have in place. You can then start to work out how much effort this will take. You will need as a minimum:
– User Requirements Document
– Functional Requirements Document
– Validation Plan
– Approved Test Scripts
– Executed Test Scripts
– Validation Report
– Change Control Procedure
– Maintenance Procedures/Manual

Of course, you will also have to maintain the validation status of the system over time, identifying what updates Microsoft have made and the impact on the validated system (repeating validation where required periodically).

If you are archiving regulatory documents using SharePoint, you will need documentation that describes how you intend to maintain the accessibility and legibility of the content over the whole retention period (likely to be 25 years) i.e. a digital preservation plan.

I think this is why the trend is for sponsors to purchase an off-the-shelf system as it can reduce significantly the amount and cost of validation activities. An apparent cost saving in the short term by use of home-built SharePoint is likely to be more expensive in the long run.

Kind regards,
Eldin.

[Eldin Rammell]

Hi Sarah

It sounds like you are describing something that is usually included in the TMF Plan. This document describes the responsibilities of each party, including TMF documents that each third party is responsible for (amongst others). If you use an eTMF that includes idenrtof expected documents or placeholders, these would usually include documents provided by the vendor too. This should be discussed with the vendor prior to study start.

Kind regards
Eldin.

[Eldin Rammell]

Hi Michal,

I agree with your conclusions. Although we often associate financial disclosure forms with FDA regulations, the requirement is not exclusive to the FDA. The artifact description in the Reference Model states:

“To document financial disclosures, certification documentation and conflicts of interest, which include but are not limited to: completed disclosure forms of financial interests and arrangements of clinical investigators”

so any form that fulfils this criteria is correctly filed here, including the new EU ‘Declaration of Interest’ form.

Kind regards,
Eldin.

[Eldin Rammell]

Hi Kai

The intention was for this artifact to hold evidence of the study-soecific validation activities. So it would not hold validation documents for the whole system (eg validation of the ePRO software itself) but rather validation of study-soecific configuration.

Kind regards
Eldin.

[Eldin Rammell]

I agree with you Shah. The notes that accompany the Model explain that each artifact also includes revisions.

[Eldin Rammell]

Hi Irene,

There is generally no regulatory requirement to file presentations in the trial master file. For this reason, there is no artifact listed in the Reference Model.

TMFs are typically closed and locked to secure the content once the trial has ended, all queries resolved and the content confirmed to be complete. As presentations may take place for a significant period of time following closure, continually adding presentations might create a data integrity risk. For this reason, they are typically filed elsewhere.

Kind regards,
Eldin.

[Eldin Rammell]

Hi Evgenia,

You are correct; retention times need to support your product registration/marketing activities. So if you plan to secure marketing approval in the EU, your retention times need to meet EU requirements, currently 25 years after closure of the trial. It is common practice for the expected retention time to be clearly shown in the clinical trial agreement with the site so that they understand their obligations right from the outset. The sponsor can provide financial support to ensure document retention but must never have direct access to the ISF or store the records on behalf of the site. Many sponsors use independent third parties to arrange storage on their behalf.

Hope this helps.

Kind regards,
Eldin.

[Eldin Rammell]

Hi Leanne

The CDISC Reference Model is not a mandatory standard so you can adapt it to suit your needs. However, most of this community would likely advise against. The model has been developed by hundreds of practitioners to reflect best practice and inspector expectations. If you make changes, you’ll likely be out of line with what the rest of industry is doing. Inspectors might struggle to find things. Other partners (eg CROs) will have similar problems. I’d advise keeping as close to the model as possible.

[Eldin Rammell]

Hi Jaclyn: So long as this question does not require you to provide confidential information, can you give a couple of examples of the type of database that you are referring to in your question? That might help to give a correct response. Thanks.

[Eldin Rammell]

Hi Tina.

There is no regulatory requirement or regulatory expectation to find publications in the Trial Master File. If you choose to file publications in the TMF, a sub-artifact of 01.10.10 might be an appropriate location, so that you have the Publication Policy and the publications themselves co-located. Having said that, per the CT Regulation, the publication policy must be included in the protocol so the use of standalone publication policies is becoming more infrequent.

It should be noted that publications often appear many years after closure of a clinical trial. Filing in the TMF may have an impact on archiving timelines and may require locked eTMFs to require unlocking simply to file a publication.

Kind regards,
Eldin.

[Eldin Rammell]

Hi Catherine

I may be mistaken but isn’t the PEP and Report device-specific, rather than being study-specific? The TMF is a study-specific collection of documents. In a device context, it is those documents that relate to a specific clinical investigation, rather than a clinical summary for the device itself, si it would not contain the PEP and Report. Perhaps I’m mistaken so happy to be corrected.

Kind regards
Eldin.

[Eldin Rammell]

Hi Kathie

Would section 01.03 be appropriate?

Eldin.

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