Trial Master Files

FDA responses to questions regarding trial master files in clinical investigations. 

From Florence’s Complete Library of FDA eRegulatory and eSource Guidance

Does an eTMF system used in conjunction with SOPs need to comply with all aspects of 21 CFR Part 11?

Yes, when it holds documents/records/eSignatures that are required by FDA regulations, part 11 controls are necessary (from 2014). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Is it acceptable to have sections of the TMF in multiple locations as long as they are retrievable?

Yes. Trail master file isn’t defined in the FDA’s regulations, so sponsors/investigators can determine the records included in it. Additionally, it may be inspected for Part 11 compliance in an inspection (from 2016). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Must original 1572s be maintained along with electronic copies in eTMF?

No, as long as you have an electronic certified copy of the 1572. There should be a SOP if you are using a certified copy as a substitute for the original (from 2015). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

During an FDA inspection, would direct access to the eTMF be required with audit trails?

No. FDA investigators may need to view the information in the system; however, this can be done by giving them direct access or having a staff member log into the system and show them the information (from 2013). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

If everything is in an eTMF is there any requirement that the original of certain documents are kept as hard copies?

Whatever is specified in the protocol would be necessary. However, it is not necessary to keep hard copies if the original files can be accessed electronically (from 2012). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Under a vendor’s eTMF system, the CRO determines who are authorized users, so who is “responsible for the content of the electronic records” that are entered by site personnel?

The sponsor/CRO. The sponsor is ultimately responsible; however, if the CRO is determining the authorizations, she/he is responsible as well. The investigator is responsible for the collection of the original source data and signing off of each case report form that accurately reflects the original source data (from 2016). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

When a sponsor collects and maintains essential documents for a clinical TMF, are signed paper documents and electronic scans of signed documents equally acceptable?

Yes as long as it follows the protocol. Additionally, during a FDA investigation, the investigator would expect to see the original files unless the copies have been certified (from 2013). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

When we follow the Essential Study Document collection and file as an eTMF, are the Clinical Trial Agreements/Budgets required to be filed with all of the required regulatory documents?

No. There are no requirements about which documents should be stored electronically. If you are not a sponsor, you should check with your sponsors of your studies to determine how you should store the study documents (from 2013). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

From Florence’s Complete Library of FDA eRegulatory and eSource Guidance

The summaries presented in our library are for informational purposes only, they are not for implementation in operations. Please consult official FDA guidance documents for operational use.