21 CFR Part 11 Compliance Software: 7 Essential Features for Pharma Companies
A batch record is approved late on a Friday. On Monday, an auditor asks who changed a test result, when the change happened, and why. If the supporting information is scattered across spreadsheets, shared logins, and printed documents, reconstructing the evidence can become difficult.
That is one reason pharmaceutical companies look for 21 CFR Part 11 compliance software. Part 11 is the US Food and Drug Administration (FDA) regulation that establishes criteria for electronic records and electronic signatures to be considered trustworthy, reliable, and generally equivalent to paper records and handwritten signatures.
Software can help organisations manage the technical controls required for electronic records. However, purchasing software does not automatically make a company compliant. Compliance also depends on intended use, system configuration, validation, procedures, employee training, and ongoing controls.
This guide explains what 21 CFR Part 11 covers and how it applies to pharmaceutical manufacturing. It also explores seven essential software features, vendor selection considerations, and the role of digital validation in supporting compliance.
What Is 21 CFR Part 11?
21 CFR Part 11 is an FDA regulation covering electronic records and electronic signatures. It establishes the criteria under which the FDA considers electronic records, electronic signatures, and handwritten signatures executed on electronic records to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper (21 CFR §11.1(a)).
The regulation is organised into three subparts:
Part 11 does not independently determine which records a pharmaceutical company must create or retain. Other applicable FDA regulations, commonly called predicate rules, set those requirements. For pharmaceutical manufacturers, these include 21 CFR Part 211, which sets out current good manufacturing practice (CGMP) requirements for finished pharmaceuticals.
Under §11.1(b), Part 11 applies to electronic records created, modified, maintained, archived, retrieved, or transmitted under FDA record requirements. It also covers certain electronic records submitted to the FDA under the Federal Food, Drug, and Cosmetic Act and the Public Health Service Act.
The FDA’s September 2003 Part 11 guidance, Part 11, Electronic Records; Electronic Signatures – Scope and Application, explains the agency’s narrower interpretation of Part 11 scope. For example, a record required under a predicate rule may fall within Part 11 when it is maintained electronically in place of paper. A record maintained in both formats may also fall within scope when the organisation relies on the electronic version to perform regulated activities.
The guidance recommends assessing records against applicable predicate rules and documenting decisions about whether electronic records fall within Part 11. The organisation's actual business practices and reliance on electronic records matter.
Part 11 distinguishes between closed and open systems based on how access to electronic records is controlled.
A closed system is one in which access is controlled by people responsible for the content of the electronic records on that system (§11.3(b)(4)).
An open system is one in which access is not controlled by people responsible for the content of the electronic records (§11.3(b)(9)).
The main distinction is the following:
Closed systems: Must use the procedures and controls described in §11.10. These include system validation, access restrictions, audit trails, and checks of authority.
Open systems: Must use procedures and controls that protect the authenticity, integrity, and, where appropriate, confidentiality of electronic records from creation to receipt. Under §11.30, these include the §11.10 controls as appropriate, along with additional measures such as document encryption and appropriate digital-signature standards when necessary.
A system's hosting arrangement alone does not determine whether it is open or closed. Organisations should assess how access is controlled and document the classification with appropriate quality and regulatory input.
7 Essential Features of 21 CFR Part 11 Compliance Software
1. Secure Electronic Records
When evaluating software, pharmaceutical companies should look beyond product descriptions and check how each feature supports their actual regulatory and operational requirements.
The following seven features map to relevant Part 11 provisions. The Part 11 requirement sections describe regulatory provisions, while the Evaluate (recommended practice) sections suggest additional points to consider when selecting software.
Why it matters:
Pharmaceutical companies manage several types of records, including batch manufacturing records, quality-control results, deviation reports, and equipment qualification documents. These records must remain authentic, complete, and accessible for their required retention periods.
Part 11 requirement:
Section 11.10 requires procedures and controls designed to protect the authenticity, integrity, and, where appropriate, confidentiality of electronic records in closed systems.
Section 11.10(b) requires the ability to generate accurate and complete copies of records in both human-readable and electronic forms suitable for FDA inspection, review, and copying.
Evaluate (recommended practice):
- Version control and document history
- Links between related quality records
- Accurate and complete record exports
- Readable copies suitable for inspection
- Protection against unauthorised record changes
2. Electronic Signatures and Signature Controls
Electronic signatures in pharma represent important decisions in GMP processes, including document review, approval, and verification.
A system should manage electronic signatures in a way that identifies the signer and preserves the relationship between the signature and the associated record.
Why it matters:
If electronic signatures can be shared, reused, or separated from their associated records, it becomes difficult to establish accountability and demonstrate who approved a particular activity.
Part 11 requirement:
Several provisions establish electronic-signature controls:
§11.50: Signed electronic records must display the signer’s printed name, the date and time of signing, and the meaning of the signature, such as review, approval, or authorship.
§11.70: Electronic signatures must be linked to their records so they cannot be excised, copied, or transferred by ordinary means.
§11.100(a): Each electronic signature must be unique to one individual and must not be reused or reassigned.
§11.100(b): The organisation must verify an individual’s identity before establishing or assigning an electronic signature.
§11.100(c): Persons using electronic signatures must certify to the FDA that the signatures are intended to be the legally binding equivalent of traditional handwritten signatures. The certification must be signed with a traditional handwritten signature and submitted in electronic or paper form.
Under §11.200(a), non-biometric electronic signatures must use at least two distinct identification components, such as an identification code and password.
The regulation also distinguishes between repeated signings during one continuous period of controlled system access and signings outside that period. The first signing during a continuous session must use all signature components; subsequent signings may use at least one component that is unique to and designed for the individual. Signings outside a single continuous session must use all required components.
Evaluate (recommended practice):
- Individual user accounts and unique credentials
- Clear signature meaning and display
- Appropriate identity verification at signing
- Controls against credential sharing
- Support for signature records and associated documentation
3. Audit Trails and Activity Tracking
An audit trail is a secure, computer-generated, time-stamped record of activities performed on electronic records. It helps organisations understand who created, modified, or deleted information and when those actions occurred.
Why it matters:
Pharmaceutical records may be reviewed long after the original activity. Without reliable activity tracking, investigating an unexpected change or reconstructing an earlier decision can become difficult.
Part 11 requirement:
Section 11.10(e) establishes the audit-trail requirement for closed systems. It calls for secure, computer-generated, time-stamped audit trails that independently record the date and time of operator entries and actions that create, modify, or delete electronic records.
Changes must not obscure previously recorded information. Audit-trail documentation must be retained for at least as long as the subject electronic records and must be available for FDA review and copying.
For open systems, §11.30 requires the §11.10 controls as appropriate.
FDA guidance:
The FDA's 2003 guidance describes its enforcement-discretion approach to certain audit-trail requirements. It also recommends considering predicate-rule obligations, documented risk assessment, product quality, and record integrity when deciding whether audit trails or other appropriate measures are needed.
Evaluate (recommended practice):
- Whether users can disable or edit audit trails
- Whether previous record information remains visible
- Whether audit trails are readable and searchable
- Whether records can be reviewed by user and date
- Whether the system supports routine audit-trail review
Capturing a reason for every change may also be useful, depending on the organisation's procedures and applicable requirements.
4. User Access Controls and Permissions
User access controls help ensure that only authorised individuals can access a system and perform activities permitted by their responsibilities.
Why it matters:
If users have access beyond their assigned responsibilities, they may be able to change records, approve activities, or perform operations without appropriate authorisation. Weak access controls can undermine the reliability of electronic records and signatures.
Part 11 requirement:
Section 11.10(d) requires system access to be limited to authorised individuals.
Section 11.10(g) requires authority checks to ensure that only authorised individuals can use the system, electronically sign records, access system operations, alter records or perform specific operations.
Section 11.300 establishes controls for identification codes and passwords, including requirements relating to uniqueness, periodic checks or revisions, and safeguards against unauthorised use.
Evaluate (recommended practice):
- Role-based access permissions
- Unique user identification
- Timely deactivation of former employees’ accounts
- Periodic access reviews
- Controls for password changes and account recovery
5. Data Integrity and Security
Why it matters:
Data integrity depends on the accuracy, completeness, and reliability of information throughout its lifecycle. In pharmaceutical manufacturing, incorrect data inputs or improperly sequenced activities can affect batch records, quality decisions, and regulatory documentation.
Part 11 requirement:
§11.10(f): Requires operational system checks to enforce the permitted sequencing of steps and events, as appropriate.
§11.10(h): Requires device checks, where appropriate, to determine the validity of the source of data input or operational instruction.
§11.30: Requires controls for open systems to protect the authenticity, integrity, and, where appropriate, confidentiality of electronic records. These include applicable §11.10 controls and additional measures, such as encryption and appropriate digital-signature standards, where necessary.
Evaluate (recommended practice):
6. Record Retention and Retrieval
Pharmaceutical companies must be able to retrieve required records when needed for quality activities, investigations, and regulatory inspections.
Software should support organised record storage and retrieval throughout the applicable retention period.
Why it matters:
Inspectors may request records created several years earlier. If information becomes inaccessible after software upgrades, system migrations, or changes in vendors, organisations may struggle to provide complete documentation.
Part 11 requirement:
Section 11.10(c) requires controls that protect electronic records and enable their accurate and ready retrieval throughout the records retention period.
Section 11.10(b) addresses the generation of accurate and complete copies in human-readable and electronic forms suitable for FDA inspection, review, and copying.
The applicable predicate rules establish the underlying record-retention obligations and periods. Part 11 should not be treated as a separate universal retention schedule.
FDA guidance:
The 2003 FDA guidance describes enforcement discretion for certain Part 11 record-retention and record-copying requirements. However, applicable predicate-rule requirements for record retention and availability remain in force.
Evaluate (recommended practice):
Search and retrieval by record type, date, or system
Export in readable and usable formats
Preservation of associated audit-trail information
Data migration and backup arrangements
Record access after system upgrades or vendor changes
7. System Validation and Documentation
System validation provides documented evidence that a computerised system performs consistently according to its intended use.
For pharmaceutical companies, validation should consider the system's functions, configuration, user roles, workflows and potential impact on product quality and record integrity.
Why it matters:
A software feature may appear to work during a demonstration but behave differently after configuration or implementation. Organisations need evidence that the system performs as intended in their actual operating environment.
Part 11 requirement:
Section 11.10(a) requires validation of closed systems to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records.
Section 11.10(k) requires appropriate controls over system documentation, including controls over documentation distribution, access and use, as well as revision and change-control procedures.
Section 11.1(e) makes computer systems, controls and attendant documentation subject to FDA inspection.
For open systems, §11.30 includes the §11.10 controls as appropriate.
Evaluate (recommended practice):
Availability and quality of vendor documentation
Release notes and software change history
Support for risk-based validation activities
Evidence for configured workflows and user roles
Documentation for system upgrades and changes
Computer system validation activities and vendor-provided documentation can support the validation process, but organisations remain responsible for demonstrating that the system is suitable for their intended use.
Industry frameworks such as GAMP 5 can provide useful guidance for a risk-based approach to computerised systems. They are industry guidance, not substitutes for applicable regulations.
How IncepOne Fits into Digital Validation and Compliance Workflows
IncepBio offers IncepOne as a digital validation and compliance software solution. IncepBio’s validation work covers commissioning, qualification, and validation (CQV), computer system validation (CSV), and computer software assurance (CSA).
When evaluating IncepOne or any digital validation solution, pharmaceutical companies should understand how its current capabilities align with their intended workflows and regulatory responsibilities.
IncepOne can be evaluated against requirements such as validation documentation, review workflows, user permissions, audit trails, electronic signatures, and record retrieval.
The availability of these specific functions should be confirmed directly with IncepBio before making a purchasing decision.
IncepOne, like any other software, does not automatically guarantee Part 11 compliance. Each organisation must assess whether the solution's controls are appropriate for its intended use, configuration, validation approach, and procedures.
Explore Digital Validation with IncepOne.
Looking to improve your pharmaceutical validation workflows? Connect with IncepBio to discuss your digital validation requirements and explore how IncepOne may support your operations.
Have questions about your validation and compliance requirements?
Conclusion
Choosing 21 CFR Part 11 compliance software requires more than comparing product features. Pharmaceutical companies must assess regulatory scope, system suitability, validation evidence, and ongoing controls to support reliable electronic records and signatures.
The right solution, supported by appropriate procedures and training, can strengthen digital validation and compliance workflows.
Frequently Asked Questions
1. What is 21 CFR Part 11 compliance software?
It provides technical controls to help regulated organisations manage electronic records and signatures in line with applicable Part 11 requirements.
2. Is 21 CFR Part 11 compliance software mandatory for pharmaceutical companies?
No specific software product is mandated. However, companies must meet applicable Part 11 requirements for electronic records and signatures within the regulation's scope.
3. What features should pharmaceutical companies look for in Part 11 software?
Key features include secure electronic records, electronic signatures, audit trails, access controls, data-integrity safeguards, record retention and retrieval, and validation documentation.
4. Does 21 CFR Part 11 require electronic signatures and audit trails?
Not every organisation must use electronic signatures. However, applicable requirements for electronic signatures and audit trails must be followed when using systems within Part 11's scope.
5. Does purchasing Part 11 compliance software automatically make a company compliant?
No. Compliance also depends on appropriate system configuration, validation, procedures, employee training, and ongoing controls.