Signatures: What’s Required for a TMF?
January 3, 2013
- eTMF Resources
Sponsors and CROs need to ensure that the processes and workflows they use in their electronic Trial Master Files (TMF) comply with all regulatory requirements, resulting in a robust system that will produce complete documentation able to withstand an agency audit.
To assist our clients, we at Wingspan often participate in discussions around which documents in an electronic Trial Master File (eTMF) really require signatures. Of course, the requirements around signatures aren’t actually related to the electronic system, but only to what’s required in predicate rules – as the FDA has made clear “Part 11, Electronic Records; Electronic Signatures — Scope and Application. Signature requirements for a TMF are established in several predicate rules – mainly Good Clinical Practice (GCP) for TMF documents, and are the same for paper and electronic documents.
The International Conference on Harmonisation (ICH) defines GCP in “GUIDELINE FOR GOOD CLINICAL PRACTICE E6(R1)”. However, the FDA considers ICH GCP only a recommendation, and does not codify GCP in a single set of regulations. Instead, regulations are scattered through the Code of Federal Regulations (CFR). It’s necessary to examine both ICH GCP and CFR sections such as those documented on the FDA’s web page “FDA Regulations Relating to Good Clinical Practice and Clinical Trials” in order to understand signature requirements.
Required Signatures for a Trial Master File
In analyzing signature requirements, we examined all of these regulations, taking into account not only specific requirements for signature, but also for review, approval or authorization.
The list of documents requiring signatures is relatively short. It includes:
- Various IRB/IEC approvals
- Informed consents signed by subjects or witnesses
- Financial Disclosure forms
- FDA 1572 Statement of Investigator
- Certain documents related to disposition of clinical supplies
- Receipt of protocol amendments
- CRFs and changes to CRFs
- Investigator Brochures
- Signature logs
In addition, sponsors may consider it a good practice to require signatures for other types of documents – but obtaining these signatures is not a GCP compliance issue unless a company SOP calls for the signatures and they are not collected.
Electronic Signatures and eTMF
Capturing all of these signatures electronically within an eTMF would require granting access to many parties – investigators, IRB/IEC members, and even trial subjects. This is a challenge for most sponsors or CROs. Emerging technology may allow documents to be digitally signed and imported into the eTMF, but for the time being, many documents will continue to be signed on paper and scanned into the eTMF.
For a complete analysis, read Wingspan’s white paper “Signature Requirements for the eTMF: A Regulatory and Technological Assessment.”