As the world is moving towards digitalization at a faster pace, the use of the computerized system in the life science industry brought a new perspective in terms of using a software application. Going digital has changed the way data is stored and managed. The transition to paperless recording has had a huge impact on the life science industry working in regulated environments. To achieve compliance, the FDA introduced a modern approach for the acceptance of electronic records and electronic signatures to be equivalent to paper records and handwritten signatures.
The companies connected to the life science industry using software applications in one or another way, have undoubtedly heard of FDA’s 21 CFR part 11 Regulation. The regulation is developed with an intent to permit the widest possible use of the electronic technology in FDA regulated industries such as pharmaceuticals, biologicals, medical devices, and clinical trials.
What do companies need to look out for while choosing an IT system software that meets compliance? Let’s break it down.
What is 21 CFR Part 11?
The FDA regulation specifies the requirements for electronic records and electronic signatures under which they are considered trustworthy, reliable, and equivalent to paper records and handwritten signatures. Specifically, it provides guidance on how a company can be compliant with the regulatory requirements for using electronic records and electronic signatures on computerized systems.
Along with the Part 11 requirements, FDA enforces all the predicate rules requirements such as Current Good Manufacturing Practices (cGMP), Good Laboratory Practices (GLP), and Good Clinical Practice (GCP) regulations.
Before diving into the specific Part 11 requirements, let’s go through the terminologies provided by FDA that will be used later as we move through –
- Electronic Records means any combination of text, graphics, data, audio, pictorial, or other information representation in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system.
- Electronic signature means a computer data compilation of any symbol or series of symbols executed, adopted, or authorized by an individual to be the legally binding equivalent of the individual’s handwritten signature.
- Digital signature means an electronic signature based upon cryptographic methods of originator authentication, computed by using a set of rules and a set of parameters such that the identity of the signer and the integrity of the data can be verified.
- Handwritten signature means the scripted name or legal mark of an individual handwritten by that individual and executed or adopted with the present intention to authenticate a writing in a permanent form. The act of signing with a writing or marking instrument such as a pen or stylus is preserved. The scripted name or legal mark, while conventionally applied to paper, may also be applied to other devices that capture the name or mark.
- Biometrics means a method of verifying an individual’s identity based on measurement of the individual’s physical feature(s) or repeatable action(s) where those features and/or actions are both unique to that individual and measurable.
- 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.
- Open system means an environment in which system access is not controlled by persons who are responsible for the content of electronic records that are on the system.
What records does Part 11 apply to?
- Records that are maintained in the electronic format in place of paper format.
- Records that are maintained in electronic format in addition to paper format that are required to support the compliance with FDA regulations.
- Electronic records to be submitted to the FDA.
- Records that are maintained under predicate rule requirements in electronic form in place of paper format.
- Electronic signatures that are intended to be equivalent to handwritten
How to comply with FDA 21 CFR part 11?
The agency focuses on the most important factor in classifying the system as closed or open. FDA places additional requirements for open systems. Let’s investigate Part 11 requirements in detail.
Control for Closed System
#01 – Validation
Persons who use closed systems to create, modify, maintain, or transmit electronic records shall employ the validation of the computerized systems with all applicable predicate rule requirements for validation.
Validation of the system must be performed to ensure accuracy, reliability, integrity, availability, consistent intended performance, and the ability to discern invalid or altered records.
Validation of the system includes methodologies such as Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) – collectively known as IQ OP PQ. Validation is an End-to-End process with a Risk Based Approach defined by FDA in GAMP 5.
#02 – Audit trail
Part 11 requires 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.
The audit trail documentation shall be retained for a period required as per the applicable predicate rule and shall be available for agency review and copying. Any changes to the existing record shall not obscure previously recorded information.
The person should comply with all the applicable predicate rule requirements related to documentation. Even if there are no predicate rule requirements to the document, audit trails must be available to ensure trustworthiness and reliability of the records.
#03 – Copies of the record
The FDA guidance says, the system must have the ability to generate accurate and complete copies of record in both human readable and electronic form suitable for inspection, review, and copying by the agency. The copies of the record can be produced in common portable electronic format as well paper copies.
#04 – Record Protection
The records must be protected to enable their accurate and ready retrieval throughout the record retention period. The records retention period should be based on the predicate rule requirement and a justified risk assessment of the value of the record over time.
The most unclear question arises if the electronic records can be deleted. As long as the predicate rule requirements are fully satisfied and the content and the meaning of the record are preserved and archived, the electronic records can be deleted. The required records can be archived in electronic format as well as paper-based format.
#05 – Access
The organization must ensure that only the right people have access to the system.
#06 – Authority Checks
The organization should 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.
#07 – Device Check
The organization should validate the source of the data input or operational instruction.
#08 – System Check
The operational system checks must be enforced to permit sequencing of the steps and events.
#09 – Personal accountability
The organization must establish or adhere to the written policies that hold individuals accountable and responsible for actions initiated under their electronic signatures, in order to deter record and signature falsification.
#10 – Personnel Qualification
The organization must have provision to determine that persons who develop, maintain, or use electronic record/electronic signature systems have the education, training, and experience to perform their assigned tasks.
#11 – Documentation Controls
The organization must establish appropriate controls over the distribution of, access to, and use of documentation for system operation and maintenance as well as revision and change control procedures to maintain an audit trail that documents time-sequenced development and modification of systems.
Control for Open system
Persons who use open systems to create, modify, maintain, or transmit electronic records shall employ 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
Open systems typically mean that more people have access to the record-keeping system, so the security requirements should be slightly more comprehensive to help ensure that the records kept are accurate and reliable.
Control for electronic signature
When electronic signatures are required, and if they are executed electronically, then compliance is needed. Following are the electronic signature requirements –
#01 – Signature component
To be compliant, an electronic signature must contain:
- Printed name of the signer
- Date and time when the signature was executed
- The meaning (e.g., authorship, review, or approval) associated with the signature
#02 – Protection against falsification
The organization must have suitable measures to prevent unauthorized use of digital signatures.
#03 – Link to document
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.
#04 – Uniqueness
Each electronic signature shall be unique to one individual and shall not be reused by, or reassigned to, anyone else.
#05 – Non-Biometric signature
Non-Biometric signatures must have two distinct identification components such as an identification code and password.
#06 – Biometric Signature
Biometric signatures shall be designed as per the biometrics methods to ensure that they cannot be used by anyone other than their genuine owners.
When using identification codes (e.g., username, initials, or number) and passwords, 21 CFR Part 11 establishes the following requirements:
- Personnel Identification: The electronic signature must be regulated in such a way that any attempted misuse of someone else’s electronic signature requires the collaboration of two or more individuals.
- Periodic Checks: Both codes and passwords must be periodically checked, recalled, or revised to ensure the security.
- Loss management: If codes, passwords, cards, etc. are lost, there must be a procedure that permits “deauthorization”.
- Security measures: Suitable measures must be in place to protect against and detect unauthorized access attempts.
- Testing: Input/output devices, including cards that bear or read authorization information, must be tested initially and periodically to ensure that they are working correctly.
21 CFR Part 11 Key Takeaways
21 CFR Part 11 provides an opportunity for Life Science companies to gain the organizational benefits of paperless record-keeping systems. It also helps the FDA ensure that when companies use electronic record-keeping systems, that document security and authenticity are adequately maintained.
Some may argue that regulations of 21 CFR Part 11 place an additional regulatory burden on these companies. In many ways, Part 11 was an acknowledgement of the inevitable movement toward the use of electronic systems in compliance.
Part 11 has been scrutinized and criticized over the years, but it remains in effect today. Given the pervasive automation of processes and digitization of data today, the regulation is more relevant than ever. Check out the validated, 21 CFR Part 11 compliant eLeaP LMS today.