Title 21 CFR Part 11 of the Code of Federal Regulations contains the regulations concerning electronic records and electronic signatures as formulated by the US Food and Drug Administration (FDA).
Since the compliant adherence to 21 CFR Part 11 is not only dependent on the software system, but also on procedural controls (e.g. document control, SOPs, training etc.) within an organization which uses electronic records, a software cannot be certified to be compliant (and any software vendor claiming a 21 CFR Part 11-compliance is incorrect!). It is, however, possible for software vendors to offer a system which meets the technical requirements for electronic records set by the FDA in a compliant set-up.
This document gives a brief overview of technical features which fulfil the requirements of 21 CFR Part 11 and facilitate its implementation within an organization. This document does not give detailed information on 21 CFR Part 11, nor does it provide legal advice for full compliance.
The full text of 21 CFR Part 11 can be found on the FDA website:
The following outline below summarizes the sections of the 21 CFR part 11 regulations which are relevant to electronic systems, also pointing out the Labstep implementation to meet these technical requirements.
Code of Federal Regulations Title 21 (FDA) - PART 11 - ELECTRONIC RECORDS - ELECTRONIC SIGNATURES
Subpart B - Electronic Records
Sec. 11.10 Controls for closed systems.
According to the FDA classification, Labstep is a closed system because the use of the electronic lab notebook requires a login and password which are both unique to the Labstep-system.
Persons who use closed systems to create, modify, maintain, or transmit electronic records shall employ procedures and controls designed to ensure the authenticity, integrity, and, when appropriate, the confidentiality of electronic records, and to ensure that the signer cannot readily repudiate the signed record as not genuine.
Authenticity: All records have only one unique/original author that cannot be
changed during the entire lifecycle of a document.
Integrity: Every single record as well as changes to a record are tracked in a full audit trail and obtain a timestamp provided by the server-system which cannot be manipulated by users. A full record of deleted documents are kept in an archive and can only be permanently deleted with proper authorization by a system admin.
Confidentiality: All records must be created within a workspace which has a finite defined list of members who are able to access the records. By default, users of an organization require an invitation to join a workspace and users from outside the organization are blocked from accessing the workspace even with an invite. Sharing rules and access rights can be further configured by the admin.
Such procedures and controls shall include the following:
Validation of systems to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records.
Validation of the Labstep system is performed internally both through automated testing and manual QA. Clients are encouraged to perform their own validation on a regular basis as well.
The ability to generate accurate and complete copies of records in both human readable and electronic form suitable for inspection, review, and copying by the agency. Persons should contact the agency if there are any questions regarding the ability of the agency to perform such review and copying of the electronic records.
💡 Agency inspectors can be added as guests to the organization on Labstep and granted access to specific workspaces with records to be reviewed. This will grant them permission to access the records either via the web-app or via the API. PDFs of records can also be exported at anytime to be reviewed outside of the platform.
Protection of records to enable their accurate and ready retrieval throughout the records retention period.
Records are protected by up-to-date cloud security best practices and are backed up daily to ensure access for the entire retention period.
Limiting system access to authorized individuals.
Access to Labstep requires authentication via a unique username and password. Access to records can be controlled, granted and revoked anytime by the organization which controls and owns these records. Additional security measures can be put in place such as IP Whitelisting and enforcing Two Factor Authentication to access the syste.
Use of secure, computer-generated, time-stamped audit trails to independently record the date and time of operator entries and actions that create, modify, or delete electronic records. Record changes shall not obscure previously recorded information. Such audit trail documentation shall be retained for a period at least as long as that required for the subject electronic records and shall be available for agency review and copying.
All records and record changes are provided with a system-created time-stamp and recorded in an activity log which cannot be manipulated by any user of Labstep. Deletion of records can be controlled and prohibited by organizational access rights and permissions.
Use of operational system checks to enforce permitted sequencing of steps and events, as appropriate.
Completion checklists can be enabled to ensure that records can only be marked as complete once all protocols have been completed and all required fields have been filled in.
Use of authority checks to ensure that only authorized individuals can use the system, electronically sign a record, access the operation or computer system input or output device, alter a record, or perform the operation at hand.
Additional to requiring a username and password at login, users can be required to enter a Two Factor Authentication code to access the system and again every time they sign a record. Every user can also be assigned a permission role within an organization which details exactly which actions they are allowed to perform on the platform.
Use of device (e.g., terminal) checks to determine, as appropriate, the validity of the source of data input or operational instruction.
A login is required from every device from which records are accessed and IP addresses of the device are stored for every session. IP whitelisting can be enabled to ensure the request is coming from a pre-authorized IP address.
Determination that persons who develop, maintain, or use electronic record/electronic signature systems have the education, training, and experience to perform their assigned tasks.
The Labstep product development team is well trained on the field of software design, implementation of cryptographic methods and regulations. Incoming Labstep team members who are not familiar with the system and the requirements are promptly provided with manuals and training.
The establishment of, and adherence to, written policies that hold individuals accountable and responsible for actions initiated under their electronic signatures, in order to deter record and signature falsification.
This feature is beyond the scope of the software system provided by Labstep and falls under the responsibility of the user. However, Labstep can provide guidelines and training to ensure compliance.
Use of appropriate controls over systems documentation including:
Adequate controls over the distribution of, access to, and use of documentation for system operation and maintenance.
Revision and change control procedures to maintain an audit trail that documents time-sequenced development and modification of systems documentation.
Sec. 11.30 Controls for open systems.
Persons who use open systems to create, modify, maintain, or transmit electronic records shall employ procedures and controls designed to ensure the authenticity, integrity, and, as appropriate, the confidentiality of electronic records from the point of their creation to the point of their receipt. Such procedures and controls shall include those identified in § 11.10, as appropriate, and additional measures such as document encryption and use of appropriate digital signature standards to ensure, as necessary under the circumstances, record authenticity, integrity, and confidentiality.
This section does not apply to Labstep because Labstep is a ‘closed system’ according to FDA definition.
Sec. 11.50 Signature manifestations.
Signed electronic records shall contain information associated with the signing that clearly indicates all of the following:
The printed name of the signer
The date and time when the signature was executed;
The meaning (such as review, approval, responsibility, or authorship) associated with the signature.
The items identified in paragraphs (a)(1), (a)(2), and (a)(3) of this section shall be subject to the same controls as for electronic records and shall be included as part of any human readable form of the electronic record (such as electronic display or printout).
Labstep provides a digital signature which indicates the printed name of the signer, a time-stamp for the signature and a statement conferring the meaning of the signature.
Sec. 11.70 Signature/record linking.
Electronic signatures and handwritten signatures executed to electronic records shall be linked to their respective electronic records to ensure that the signatures cannot be excised, copied, or otherwise transferred to falsify an electronic record by ordinary means.
Digital signatures in Labstep as well as their authors and time-stamps are forever recorded in the activity log and can only be altered by persons with the appropriate authority. Digital signatures are displayed in the review section of each experiment entry, and are exported as well during a PDF export.
Subpart C - Electronic Signatures
Sec. 11.100 General requirements.
***(a) Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to, anyone else.
Any combination of username and password in Labstep is unique. Since electronic signatures are linked to the username/password combination, they can be used only by one individual per signature.
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.
Labstep can be configured to require the user to enter a Two Factor Authentication code from a pre-authorized device to confirm their identity every time they sign.
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.
The certification shall be signed with a traditional handwritten signature and submitted in electronic or paper form. Information on whereto submit the certification can be found on FDA’s web page on Letters of Non-Repudiation Agreement.(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.
Sec. 11.200 Electronic signature components and controls.
Electronic signatures that are not based upon biometrics shall:
Employ at least two distinct identification components such as an identification code and password.
When an individual executes a series of signings during a single, continuous period of controlled system access, the first signing shall be executed using all electronic signature components; subsequent signings shall be executed using at least one electronic signature component that is only executable by, and designed to be used only by, the individual.
When an individual executes one or more signings not performed during a single, continuous period of controlled system access, each signing shall be executed using all of the electronic signature components.
Be used only by their genuine owners; and
Be administered and executed to ensure that attempted use of an individual’s electronic signature by anyone other than its genuine owner requires collaboration of two or more individuals.
Electronic signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other than their genuine owners.
Labstep can be configured such that, in order to create a first signature the user must login with their username and password and enter the Two Factor Authentication code to sign. In subsequent signings only the Two Factor Authentication code is required. A session timeout can be configured to ensure that after a set period of time the user must once again enter their username and password (and 2FA code if enabled) to gain access to the system and begin signing again.
Labstep does not use biometrics.
Sec. 11.300 Controls for identification codes/passwords.
Persons who use electronic signatures based upon use of identification codes in combination with passwords shall employ controls to ensure their security and integrity. Such controls shall include:
Maintaining the uniqueness of each combined identification code and password, such that no two individuals have the same combination of identification code and password.
Two Factor Authentication codes are generated by cryptographic algorithms which ensure that, at any one time, it is virtually impossible for two users to have the same combination of code and password.
Ensuring that identification code and password issuances are periodically checked, recalled, or revised (e.g., to cover such events as password aging).
The Two Factor Authentication code rotates every 60 seconds. Changing of passwords is facilitated by the Labstep system but is left at the discretion of the organization to decide and implement a schedule for users to update their passwords.
Following loss management procedures to electronically deauthorize lost, stolen, missing, or otherwise potentially compromised tokens, cards, and other devices that bear or generate identification code or password information, and to issue temporary or permanent replacements using suitable, rigorous controls.
Passwords can be reset by the user as soon as they suspect it might have been compromised. Access tokens can also be revoked.
Use of transaction safeguards to prevent unauthorized use of passwords and/or identification codes, and to detect and report in an immediate and urgent manner any attempts at their unauthorized use to the system security unit, and, as appropriate, to organizational management.
Labstep provides organization admins access to security logs which detail the time, device details and IP address of any login or system activity, in order to monitor for suspicious activity. IP whitelisting can also be used to prevent unauthorized use of passwords in the first place.
Initial and periodic testing of devices, such as tokens or cards, that bear or generate identification code or password information to ensure that they function properly and have not been altered in an unauthorized manner.
This feature is beyond the scope of the software system provided by Labstep. However, Labstep can provide guidelines and training to ensure compliance.
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