Signatures

FDA responses to questions regarding signatures in clinical investigations. 

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

What is considered an acceptable electronic method for collecting eSignatures?

An acceptable method follows these guidelines:

1. Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to, anyone else.
2. Before an organization establishes, assigns, certifies, or otherwise sanctions an individual’s electronic signature, or any element of such electronic signature, the organization shall verify the identity of the individual.
3. Persons using electronic signatures shall, prior to or at the time of such use, certify to the agency that the electronic signatures in their system, used on or after August 20, 1997, are intended to be the legally binding equivalent of traditional handwritten signatures.
   1. The certification shall be submitted in paper form and signed with a traditional handwritten signature, to the Office of Regional Operations (HFC-100), 5600 Fishers Lane, Rockville, MD 20857.
   2. Persons using electronic signatures shall, upon agency request, provide additional certification or testimony that a specific electronic signature is the legally binding equivalent of the signer’s handwritten signature.

(from 2014). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

What methods may be used to create valid electronic signatures?

There are no mandated methods and part 11 regulations permit a wide variety of methods (from 2017). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

How should sponsors and regulated entities verify the identity of the individual who will be electronically signing records as required in 21 CFR 11.100(b)?

There is no specified method from the FDA and the agency accepts many methods (from 2017). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

When an individual executes a series of signings during a single, continuous period of controlled system access, could the initial logging into an electronic system using a unique username and password be used to perform the first signing and satisfy the requirements found in 21 CFR 11.200(a)?

No. All signatures during the period of controlled system access can be performed using the password alone, but it does require the password be entered (from 2017). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

What requirements must electronic signatures based on biometrics meet to be considered an accepted biometric method?

Electronic signatures based on biometrics must be designed to ensure that they cannot be used by anyone other than their genuine owners. They are accepted as long as they meet the requirements in part 11 (from 2017). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Does FDA certify electronic systems and methods used to obtain electronic signatures?

No (from 2017). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Are there any essential study documents that cannot be signed electronically?

No. There are no FDA regulatory requirements that signatures for required records/reports be kept on paper or in a digital/electronic format, as long as they are accurate, complete, and current (from 2016). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Is it an FDA requirement to have wet signatures for certain documents? If there are, is it acceptable to keep a copy of these documents?

There are no restrictions for which documents are maintained electronically or signed with eSignatures. A site should have procedures defined for validating eSignatures. If certain documents have wet signatures, and the site wishes to only have copies, they must be certified copies and it is recommended to have clear SOP for certifying copies (from 2015). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Have eSignatures been used for regulatory documents and audited by the FDA? What have been the pitfalls?

Yes they have been used and audited. The main things you need to ensure when implementing is that you have a secure process to authenticate signers, program timeouts/logs-outs so users must re-enter their password to gain access to the system, link eSignatures to the document signed, implement safeguards to immediately detect/report unauthorized attempts to sign, have a process for an emergency to allow a person to authorize another person to use his/her signature, have an audit trail showing when a document was signed and who signed it, and have the ability to have multiple signers for a document (from 2016). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Is there special software equipped to recognize and verify the validity of eSignatures on documents?

No; there is no special software required for the sponsor and the responsibility falls on your institution to meet the regulatory criteria (from 2014).  Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

If someone logs on to an electronic system using a username and password, is it necessary for the user to re-enter the username when executing a series of signings?

No, you only need to enter your password as long as it’s during a single, continuous period of controlled system access (from 2016). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Does combining wet ink signatures and eSignatures on the same document violate 21 CFR Part 11.70?

This should be fine, the FDA regulations are not that specific with regard to eSignatures. There are no restrictions on which documents are maintained electronically or signed with eSignatures, but the FDA may look for the site’s procedures for validating eSignatures during an inspection (from 2015). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Do we need to send a certification document to the FDA every time we hire a new employee that will be using our eSignature system?

No. A single certification may be stated in broad terms that encompass electronic signatures of all current and future employees. A certification of a particular eSignature may be necessary if the agency requests it (from 2016).  Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Is it acceptable to provide our eSignature policy and verification process to an FDA inspector only once they visit our office for an inspection?

No, the initial certification should be given to the FDA as a matter of record. The affected parties chose who submits the certification (from 2016). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Is a written statement with wet ink signature from investigators necessary to confirm their acknowledgment that their eSignature is their wet ink equivalent?

Not necessarily. There is no formal FDA regulation for this process; however, you should have clear procedures for validating eSignatures because they will check that you are following those in a bioresearch monitoring inspection (from 2013). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Can logging into the network to gain access to the restricted location housing the blank forms count as one of the signature components?

Yes. If an individual logs into an electronic system using a username and password, it isn’t necessary to re-enter the username when an individual executes a series of signings during a single, continuous period of controlled system access (from 2016). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Are scanned versions of signatures considered as acceptable?

Yes. Scanning copies of original documents does not conflict with FDA regulatory requirements. It is recommended to develop a SOP with instructions about how the original document with the wet signature will be obtained (from 2014). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Can a DOA log only consist of electronic signatures and the PI’s electronic approval signature stamp on the final page?

Yes, it should not conflict with FDA regulations. The suggested route is to develop SOPs for the use of electronic signatures and stamps (from 2016).  Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Does signing a true signature on a tablet comply with regulations?

It can. The basic approach of linking a subject-applied signature to an electronic consent form using a computer tablet’s stylus feature can be considered part 11 compliant if consistently used correctly as intended (from 2014).  Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Can an image copy of a signature be used instead of hand signing documents?

No. This is not considered an eSignature, and it provides no measure of security or assurance that the signatory actually drafted/reviewed/approved the document (from 2012).  Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Is it an acceptable approach for a user to sign in to a secure data management system with their ID and password, and then only requiring the password to execute eSignatures during that log-in session?

Yes, this should be Part 11 compliant (from 2013).  Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

If we capture signatures electronically on contracts with our investigator sites does it have to be in compliance with part 11?

Yes. For records required to be maintained but not submitted to FDA, electronic records can be used instead of paper records or electronic signatures in lieu of traditional signatures, in whole or in part, provided that the requirements of part 11 are met (from 2012).  Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Can an investigator sign a contract using an electronic signature that is cut and pasted from a pdf file?

No. This doesn’t seem like it would comply with Part 11 (from 2012).  Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Is it acceptable to obtain electronic signatures for the consent form?

Yes, as long as they comply with FDA’s regulations (from 2012).  Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

We don’t have a Part 11 eSignature validation system in place, but can a picture of a signature be a placeholder for the wet signature that would later be used for the file?

If you don’t have a Part 11 eSignature validation system in place, this method probably doesn’t work. Since the FDA doesn’t have clear regulations on this, create SOPs to help with this decision (from 2016). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

Can a PI use their eSignature for a Clinical Study Agreement with a pharmaceutical?

Maybe. eSignatures are allowed under FDA regulations, but cannot be used if they conflict with FDA regulatory requirements (from 2014). Documentation in the Florence Library of FDA eRegulatory and eSource Guidance

For an IND study, if a research study drug is ordered through a computerized medication ordering system, does 21 CFR Part 11 apply to the physician’s electronic signature for the research medication order?

No. These signatures are not normally signatures required under FDA regulations in 21 CFR, so part 11 doesn’t apply (from 2012). 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.