21 CFR Part 11 rule compliance

Definition of 21 CFR Part 11 rule 

21 CFR Part 11 establishes the criteria under which electronic records and electronic signatures will be considered equivalent to paper records and handwritten signatures.The rule applies to records in electronic form that are created, modified, maintained, archived, retrieved, or transmitted under any records requirements set forth in FDA regulations.

Definition of closed system

An environment in which system access is controlled by persons responsible for the content of electronic records on the system.

Definition of open system

An environment in which system access is not controlled by persons responsible for the content of electronic records on the system.

Overview

In order to comply with 21 CFR Part 11, a number of requirements must be met:

  • Any computer system utilizing electronic records and signatures must be validated to ensure its accuracy, reliability, and consistent intended performance.
  • These computer systems must maintain an audit trail that is secure, computer-generated, date/time stamped, available for review, and lists the person making the change along with the original and changed data.
  • These computer systems must also use authority checks to ensure that only authorized individuals can use the system, alter records, and perform various operations.
  • The customer must use the existing security features within the computer systems to limit access.
  • The customer must establish and follow written policies that hold its employees accountable for their actions.
  • The customer must retain records in a relational database protected by system security. Policies and procedures must be established to ensure that records are retained for the appropriate duration of time.
  • The customer must verify the identity of the individual before assigning him or her an electronic signature. A customer is responsible for certifying, in writing, to the FDA that it intends to user the individual’s electronic signature as the legally binding equivalent of his or her handwritten signature.

The following table defines the requirements for the FDA’s Title 21 – Code of Federal Regulations – Part 11 Rule (21 CFR Part 11), and describes how Hertzler’s GainSeeker products help you fulfill the requirements.

Subpart B
Section 11.10 Controls for Closed Systems
Requirements Solution

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:

Customers are responsible for developing procedures to support the use of the applications in a regulated environment.

(a)Validation of systems to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records.

Customers must validate the applications. Customers may develop and/or execute the validation plans and protocols themselves or out-source these activities. The validation should follow an established system life cycle (SLC) methodology.

(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.

Records are maintained in a relational database and may be retrieved using the applications or a variety of third-party data retrieval tools, such as Crystal Reports or Microsoft Access.

(c)Protection of records to enable their accurate and ready retrieval throughout the records retention period.

Records are maintained in a relational database and are protected via system security.Customers should establish policies and procedures to ensure that records are retained for an appropriate amount of time.

(d)Limiting system access to authorized individuals.

To limit system access, the applications should be configured to use the built-in security mechanisms.The account policies should implement password aging, minimum password length, password uniqueness, and account lockout after a reasonable number of unsuccessful login attempts.

Internal application security should be used to limit user access to authorized security areas and applications.The data collection templates should be configured to use the Logout command to automatically log out the user from the system after the data collection is completed.

 

(e)Use of secure, computer­generated, time­stamped 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 audit trail records include a date/time stamp, node of origination, operator name, and action taken.

A “Reason” description should be included with each audit trail record.

Customers should implement a third-party clock synchronization utility to ensure that all date/time stamps are accurately recorded in the audit trail.

 

(f)Use of operational system checks to enforce permitted sequencing of steps and events, as appropriate.

Customers should employ password security checks in their document delivery interfaces.

(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.

To limit system access, the applications should be configured to use the built-in security mechanisms.The account policies should implement password aging, minimum password length, password uniqueness, and account lockout after a reasonable number of unsuccessful login attempts.

Internal application security should be used to limit user access to authorized security areas and applications. The data collection templates should be configured to use the Logout command to automatically log out the user from the system after the data collection is completed.

 

(h)Use of device (e.g., terminal) checks to determine, as appropriate, the validity of the source of data input or operational instruction.

To ensure the validity of the source of data input, customers should install the appropriate application modules at each workstation. The application’s client/server architecture facilitates data storage at the database server, ensuring that the audit trail is generated from a single location.

(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.

Customers are responsible for ensuring that all persons involved with the regulated systems have the necessary levels of education, training, and experience to perform their assigned tasks.

(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.

Customers are responsible for developing policies and procedures to support the use of the applications in a regulated environment.

(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.

Hertzler Systems Inc. provides system operation and maintenance manuals for all the audited applications to its customers upon purchase. The manuals are on CD­ROM in read-only format and cannot be modified by the customer.

Although customers are not responsible for control over the content of system operation and maintenance manuals, they should establish and maintain controls over the distribution of, access to, and use of that documentation.

 

(2)Revision and change control procedures to maintain an audit trail that documents time­sequenced development and modification of systems documentation.

Revisions made to the manuals by Hertzler staff follow a documented change control procedure.
Section 11.30 Controls for Open Systems
Requirements Solution

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 Section 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.

Customers are responsible for developing procedures to support the use of the applications in a regulated environment.
Section 11.50 Signature Manifestations
Requirements Solution

(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

All audit trail records include date/time stamp, node of origination, operator name, and action taken.

(2)The date and time when the signature was executed;

All audit trail records include date/time stamp, node of origination, operator name, and action taken.

(3)The meaning (such as review, approval, responsibility, or authorship) associated with the signature.

All audit trail records include a text field describing the action taken.This field can be used to determine the meaning of the action.

(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).

Records are maintained in a relational database and may be retrieved using the applications or a variety of third-party data retrieval tools, such as Crystal Reports or Microsoft Access.

The metadata (retrieval information, e.g. date/time range, and filter contents, if any) is always included with the data.

 
Section 11.70 Signature/record linking
Requirements Solution

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.

Each audit trail record includes the name of the operator linked to the specific activity. Customers should also establish policies and procedures to prevent unauthorized access to the audit trail file.
 Subpart C
Section 11.100 General requirements
Requirements Solution

(a)Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to, anyone else.

Hertzler application security does not permit the creation of duplicate user IDs.Customers using the applications in a regulated environment must be responsible for ensuring that electronic signatures are unique to one individual and not reused by or reassigned to any other individual

(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.

Customers using the applications in a regulated environment must be responsible for verifying the identities of individuals using electronic signatures.

(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.

Customers using the applications in a regulated environment must be responsible for certifying to the agency that the electronic signatures in their system 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.

Customers using the applications in a regulated environment must be responsible for certifying to the agency that the electronic signatures in their system are intended to be the legally binding equivalent of traditional handwritten signatures.

(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.

Customers using the applications in a regulated environment must be responsible for certifying to the agency that the electronic signatures in their system are intended to be the legally binding equivalent of traditional handwritten signatures.
Section 11.200 Electronic signature components and controls
Requirements Solution

(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.

Hertzler application security employs a user ID and password combination to identify a user.

(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.

To indicate the start of a continuous period of controlled system access, the user must use two distinct identification components to log in.Subsequent signatures during this period will be recorded using only the user ID component of the signature.

The data collection templates should be configured to use the Logout command to automatically log out the user from the system after data collection is completed.

Customers should also implement policies and procedures requiring users to log out of non-data entry applications during periods of non­use.

(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.

The data collection templates should be configured to use the Logout command to automatically log out the user from the system after data collection is completed.

Customers should also implement policies and procedures requiring users to log out of non-data entry applications during periods of non­use.

(2)Be used only by their genuine owners;

Customers using the applications in a regulated environment must be responsible for ensuring that non­biometric electronic signatures are used only by their genuine owners.

(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.

Customers using the applications in a regulated environment must be responsible for ensuring that attempted use of an individual’s electronic signature by anyone other than its genuine owner requires collaboration of two or more individuals.

(b)Electronic signatures based upon biometrics shall be designed to ensure that they cannot be used by anyone other than their genuine owners.

Biometric devices are readily available from third-party vendors. However, customers using the applications in a regulated environment, or any organization that may develop biometric devices for interfacing with the audited applications, must be responsible for ensuring that electronic signatures based upon biometrics are designed to ensure that they cannot be used by anyone other than their genuine owners.
Section 11.300 Controls for identification codes/passwords
Requirements Solution

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.

Hertzler application security maintains the uniqueness of each user ID and password combination.

(b)Ensuring that identification code and password issuances are periodically checked, recalled, or revised (e.g., to cover such events as password aging).

Hertzler application security contains functionality for password aging.

(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.

Customers using the applications in a regulated environment must be responsible for employing controls to ensure the security and integrity of identification codes and passwords.

(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.

The Hertzler Login routine generates an alarm after three unsuccessful login attempts and records the login attempt to the audit trail.

(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.

Customers using the applications in a regulated environment, or any organization that may develop devices that bear or generate identification code or password information to interface with the audited applications, must be responsible for ensuring that devices that bear or generate identification code or password information be tested to ensure that they function properly and have not been altered in an unauthorized manner.