FDA 21 CFR part 11 compliance

How does DCTrials comply with FDA 21 CFR part 11?

Clause DCT Compliance
11.1 Scope
(a) The regulations in this part set forth the criteria under which the agency considers electronic records, electronic signatures, and handwritten signatures executed to electronic records to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper.
(b) This part applies to records in electronic form that are created, modified, maintained, archived, retrieved, or transmitted, under any records requirements set forth in agency regulations. This part also applies to electronic records submitted to the agency under requirements of the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act, even if such records are not specifically identified in agency regulations. However, this part does not apply to paper records that are, or have been, transmitted by electronic means.
(c) Where electronic signatures and their associated electronic records meet the requirements of this part, the agency will consider the electronic signatures to be equivalent to full handwritten signatures, initials, and other general signings as required by agency regulations, unless specifically accepted by regulation(s) effective on or after August 20, 1997.
(d) Electronic records that meet the requirements of this part may be used in lieu of paper records, in accordance with 11.2, unless paper records are specifically required.
(e) Computer systems (including hardware and software), controls, and attendant documentation maintained under this part shall be readily available for, and subject to, FDA inspection.
(f) This part does not apply to records required to be established or maintained by 1.326 through 1.368 of this chapter. Records that satisfy the requirements of part 1, subpart J of this chapter, but that also are required under other applicable statutory provisions or regulations, remain subject to this part.
DCTrials software utilization fits in the 21 CFR Part 11 scope.
11.2 Implementation
(a) For records required to be maintained but not submitted to the agency, persons may use electronic records in lieu of paper records or electronic signatures in lieu of traditional signatures, in whole or in part, provided that the requirements of this part are met.
(b) For records submitted to the agency, persons may use electronic records in lieu of paper records or electronic signatures in lieu of traditional signatures, in whole or in part, provided that:
(1) The requirements of this part are met; and The document or parts of a document to be submitted have been identified in public docket No. 92S-0251 as being the type of submission the agency accepts in electronic form. This docket will identify specifically what types of documents or parts of documents are acceptable for submission in electronic form without paper records and the agency receiving unit(s) (e.g., specific center, office, division, branch) to which such submissions may be made. Documents to agency receiving unit(s) not specified in the public docket will not be considered as official if they are submitted in electronic form; paper forms of such documents will be considered as official and must accompany any electronic records. Persons are expected to consult with the intended agency receiving unit for details on how (e.g., method of transmission, media, file formats, and technical protocols) and whether to proceed with the electronic submission.
DCT offers gives the customer/sponsor the tools to implement and respect 21 CFR part 11 requirements, as described in following rows:DCTrials provides electronic records like raw data, calculated data, audit trail, configuration settings, Audit trail report in PDF format, Data export in Excel, Access or TXT format, etc.The implementation of 21 CFR part 11 is the responsibility of DCT.
11.3 Definitions
[…] (4) Closed system means an environment in which system access is controlled by persons who are responsible for the content of electronic records that are on the system. […]
DCTrials is a closed system
11.10 Controls for closed systems
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. Such procedures and controls shall include the following:
Controls for closed system are provided by IT operators of the system application with a security based on Windows authentication system. Procedures are managed by DCT’s SOPs.
(a) Validation of systems to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records. DCTrials cycle of life describes the validation phases required to ensure them.
(b) 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. The eCRF provides tools for creating partial/total exports of the clinical database. The tools provided to both physicians and monitors allow the inspection of the data collected the review the audit trail of changes, generating accurate, complete and presented in a human-readable format electronic records.
c) Protection of records to enable their accurate and ready retrieval throughout the records retention period. Both the clinical database and the related information are only reachable after validation of the user into the eCRF. No open/public areas are allowed. The company follows the corresponding SOPs regarding data backup policies and security of computerized system. All electronic records can be maintained in the active database or archived to accommodate all required retention periods. Access to these records is also secured using the SOPs previously mentioned in this point.
(d) Limiting system access to authorized individuals. Username/password authentication is used for final users of the system. IT operators and other personnel at DCT are provided access to their related sections depending on their role’s properties and grants.
(e) 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. An automatic audit trail is recorded and it is part of the clinical database, registering for each user action: date and time, printed name of user who causes the action, variable affected, old and new value and reason for change. The audit trail exists as long as the eCRF is kept operational. Its information can be printed.
(f) Use of operational system checks to enforce permitted sequencing of steps and events, as appropriate. A set of data checks/queries can be provided to the eCRF so that they can be applied in real time. The eCRF will also record the answer of the physicians to the response of this validation plan.
(g) 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. Only authenticated final users are able to use the system. Records pertaining to registered clinical data cannot be modified by DCT staff.
(h) Use of device (e.g., terminal) checks to determine, as appropriate, the validity of the source of data input or operational instruction. DCTrials is offered as a tool reachable through internet, no terminal restrictions are implemented.
(i) 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 personnel at the company involved in the design/modifications of the eCRF have been trained following an internal SOP, which covers this issue. The production servers are maintained by a third party, a professional Spanish hosting company. ISO certificates for this company are available.
(j) 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. The company follows an internal SOP regarding the design of the CRFs in which is described the procedures for managing user accounts, password retrieval as well as prevention policies such as password ageing.
(k) Use of appropriate controls over systems documentation including:
(1) Adequate controls over the distribution of, access to, and use of documentation for system operation and maintenance.
(2) Revision and change control procedures to maintain an audit trail that documents time- sequenced development and modification of systems documentation.
DCT staff involved in this tasks track and document changes for every eCRF.
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.
The company has based the eCRF in closed systems.
(a) Signed electronic records shall contain information associated with the signing that clearly indicates all of the following:
1) The printed name of the signer;
2) The date and time when the signature was executed; and
3) The meaning (such as review, approval responsibility, or authorship) associated with the signature. (b) 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).
This information is registered by the system in the clinical database and can be tracked for changes made by physicians, automatic queries, manual queries and data validation.
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.
All the electronic records contain the ID of its author. This ID is generated when a new user account is created for a given clinical study, and it allows linking the data collected with the name of the author.
(a) Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to, anyone else.
Every user has a unique ID in a given study. The design of the process that creates user accounts guaranties that the combination of user ID/password is unique at any point in time.
(b) 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. The link between user account and data registered explained in point (a) of this section allows this kind of verifications.
(c) 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 eCRF is not using external or third party signatures. Each user is assigned a unique ID, for a given trial, which will be added to any electronic record that he is responsible for.
(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. 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. It is the responsibility of the customer/contractor to ensure that before they verify the identity of the user (physicians, monitors or any other existing role) before they order assigning a user id to that individual.
(a) Electronic signatures that are not based upon biometrics shall:
(1) Employ at least two distinct identification components such as an identification code and password.
(i) 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.
(ii) 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.
(2) Be used only by their genuine owners; and
(3) 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.
The eCRF uses user ID/password combination for granting access to the system.The eCRF logon process requests the user ID and the password every time the user first logs in to the system. He/she will not be asked for extra signings while the working session is active. The eCRF forces the user to log on with the user id and password every time a new session is initiated or when an existing one is timed out. The customer/contractor is the responsible of informing that user IDs and passwords shall be used only by the genuine owner of the signature. The customer must clearly explain to the users that sharing electronic signatures with others is forbidden and may involve sanctions. The company is not using identification based on biometric systems at the moment.
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:
(a) Maintaining the uniqueness of each combined identification code and password, such that no two individuals have the same combination of identification code and password.
It is guaranteed by the new user account generation process, which is described in an internal SOP of the company.
(b) Ensuring that identification code and password issuances are periodically checked, recalled, or revised (e.g., to cover such events as password aging). Password aging is enforced in every clinical study.
(c) 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. Upon detecting that an electronic signature may have been compromised, the electronic signature can be immediately deactivated in the eCRF. The company will assist the customer identifying the source/authors of the problem and managing the creation of a new signature if needed.
(d) 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. After three invalid logon attempts the eCRF will redirect out the user from the logon process. The user is then forced to close the web browser and reconnect it to the corresponding web address.
(e) 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. Our eCRF is not using any devices for generating the electronic signatures.