21 CFR Part 11 Open vs. Closed System: Examples, Controls, and Key Differences

21 CFR Part 11, established by the U.S. Food and Drug Administration (FDA), governs the use of electronic records and electronic signatures in FDA-regulated industries such as pharmaceuticals, medical devices, and biotechnology. 21 CFR Part 11 ensures that electronic records and e-signatures are authentic, reliable, and equivalent to paper records. It defines the technical and procedural controls organizations must implement to remain compliant.

A core distinction between open systems and closed systems is outlined in 21 CFR 11.3. An open system, per 21 CFR 11.3(b)(9), is an environment where system access to electronic records is not controlled by those responsible for the record content. Conversely, a closed system, defined in 21 CFR 11.3(b)(4), is one in which access to electronic records is controlled by personnel responsible for the content of the records.

Controls for closed systems under 21 CFR Part 11.10 include requirements for computer system validation (CSV), access limitations, audit trails, record protection, electronic signatures, training, and more. For open systems, 21 CFR Part 11.30 requires the implementation of all applicable controls specified in 21 CFR Part 11.10, together with additional safeguards, such as document encryption and digital signature implementation, to ensure record authenticity and integrity. These enhanced security measures address the increased risk associated with external or uncontrolled access.

Distinguishing between open and closed systems in regulated environments is essential because these differences directly influence compliance strategies, validation processes, and approaches to maintaining data integrity within regulated organizations.

To meet these requirements for open or closed systems, many life science companies adopt purpose-built software designed for 21 CFR Part 11 compliance. SimplerQMS is a fully validated, cloud-based electronic Quality Management System (eQMS) designed for life science companies. SimplerQMS enables life science organizations to manage records securely, reduce compliance risks, and maintain readiness for FDA, ISO, and EU requirements by centralizing key processes, including document control, CAPA, audits, change management, training management, and more.

SimplerQMS embeds all necessary 21 CFR Part 11 controls, including secure role-based access, audit trails, electronic signatures, GAMP 5–aligned validation, encryption protocols, and more, ensuring full alignment with 21 CFR Part 11 requirements.

What Is a Closed System?

A closed system is defined by the FDA 21 CFR 11.3(b)(4) as an environment in which system access is controlled by individuals responsible for the content of electronic records on the system. Access is restricted to authorized personnel, and their actions are tracked through secure audit trails. Closed systems are widely used in the life sciences as they safeguard sensitive data and ensure data integrity.

Essential characteristics of a closed system, according to FDA 21 CFR Part 11, include strict access controls that limit use to personnel authorized and approved by system administrators. All user actions are tracked through secure, computer-generated, time-stamped audit trails, and authority checks are enforced to ensure only qualified individuals can perform specific tasks.

The system itself must be validated to confirm accuracy, reliability, and consistent intended performance. Records are safeguarded to allow accurate retrieval throughout their entire retention period.

What Are the Examples of Closed Systems?

Various examples of closed systems are as follows.

• Document Management Systems (DMS): DMS is used to manage controlled documents such as standard operating procedures (SOPs), training materials, and other documents. DMS usually has version control, electronic approvals, and restricted access permissions.
• Quality Management System (QMS) Software or Electronic QMS: QMS or eQMS software supports compliance-related processes, including deviations, CAPA (Corrective and Preventive Actions), audits, and employee training. QMS or eQMS helps ensure that all quality data is captured and controlled within a validated environment.
• Enterprise Resource Planning (ERP) Systems: ERP systems integrate and control key business operations such as inventory, procurement, and production planning. ERP systems enforce user access control and audit logging for system accountability.
• Customer Relationship Management (CRM) systems: CRM systems can be used to manage GxP-relevant records, such as customer complaints or adverse events, within a closed and regulated IT environment. CRMs ensure the secure capture, storage, and retrieval of these records.
• Product Lifecycle Management (PLM) systems: PLM systems oversee the design, development, and engineering change control of products. PLM systems often allow maintaining strict access control, document versioning, and change history tracking.
• Laboratory Information Management Systems (LIMS): LIMS handle laboratory workflows, sample tracking, and analytical data management.LIMS streamlines operations and ensures data integrity across lab processes.
• Electronic Laboratory Notebooks (ELN): ELNs are used to capture scientific research data. Experimental records are timestamped, traceable, and accessible only to authorized users.
• Clinical Trial Management Systems (CTMS): CTMS manages clinical study planning, site management, and trial documentation. Validated controls ensure compliance with Good Clinical Practice (GCP) and audit readiness.
• Manufacturing Execution Systems (MES): MES controls real-time production workflows, equipment status, and operator activities. MES provides full traceability of manufacturing operations.
• Electronic Batch Record (EBR) systems: EBR systems document and control batch manufacturing data. EBR systems enforce workflows, perform automated checks, and apply electronic signatures for GMP compliance.
• Electronic Data Capture (EDC) systems: EDC systems collect and manage clinical trial data directly from investigators or sites. EDC supports efficient, accurate, and compliant data capture.
• Regulatory Information Management Systems (RIMS): RIMS tracks and manages regulatory submissions, approval status, and correspondence with agencies. RIMS centralizes compliance information to support regulatory readiness.

Within the life sciences context, these examples are typically implemented as closed systems under 21 CFR Part 11, where internal access controls are in place. Cloud-hosted or externally accessed implementations of these systems would be considered open systems and may require additional technical and procedural safeguards to ensure compliance.

What Are the Key Controls for Closed Systems?

The key controls for closed systems under 21 CFR Part 11.10 are outlined below.

• Computer System Validation (21 CFR 11.10(a)): CSV is a process to ensure that the system consistently produces accurate, reliable, and intended results, and can detect invalid or altered records. CSV is fundamental to maintaining system integrity in GxP environments.
• Accurate and Complete Records (21 CFR 11.10(b)): The system must be capable of generating accurate and complete copies of electronic records in both human-readable and electronic form. This ensures accessibility for FDA inspection, audits, review, and copying.
• Record Protection (21 CFR 11.10(c)): Records must be safeguarded to preserve their integrity and enable accurate retrieval throughout their retention period, supporting long-term compliance with regulatory and legal requirements.
• Access Limitation (21 CFR 11.10(d)): Access must be restricted to authorized individuals through role-based access controls (RBAC) and authentication measures to prevent unauthorized record manipulation.
• Audit Trails (21 CFR 11.10(e)): Secure, computer-generated, time-stamped audit trails must track record creation, modification, and deletion to provide accountability and traceability.
• Operational Checks (21 CFR 11.10(f)): The system can implement workflow enforcement controls that ensure correct sequencing of process steps, minimizing errors in regulated operations.
• Authority Checks (21 CFR 11.10(g)): The system must verify that only authorized personnel can perform restricted actions or apply electronic signatures, protecting the integrity of decision-making and record approval.
• Device Checks (21 CFR 11.10(h)): Input devices, instruments, and operational instructions must be validated to ensure data entered into the system is accurate and reliable, preventing the introduction of corrupt or false data.
• Training and Qualification (21 CFR 11.10(i)): Personnel must have documented education, training, and experience to competently and compliantly operate within the system.
• Accountability Policies (21 CFR 11.10(j)): Accountability policies hold individuals responsible for actions taken under their unique electronic signatures.
• Documentation Controls (21 CFR 11.10(k)): Comprehensive procedural documentation, revision control, and change tracking must be maintained to ensure traceability and auditability of system operations.

What Is an Open System?

An open system is defined in FDA 21 CFR Part 11.3(b)(9) as an environment where system access is not controlled by the individuals responsible for the content of electronic records.

Open systems may allow broader access, including the creation of user accounts without direct administrator approval. While convenient, open systems introduce security risks and make it more challenging to ensure that records remain accurate and reliable. Organizations that utilize open systems must implement robust safeguards, such as strong access controls, encryption, digital signatures aligned with Part 11 requirements, and secure audit trails, to protect data integrity.

What Are the Examples of Open Systems?

Several examples of open systems are as follows.

• Cloud Storage Services: Externally hosted platforms that allow users to upload, store, and share files over the internet may function as open systems when access and infrastructure are managed outside the record-owning organization. Online platforms such as Dropbox, Google Drive, or WeTransfer may be considered open systems.
• Web-based Regulatory Submission Portals: Systems used to submit or exchange regulatory data with health authorities or external partners such as the FDA Electronic Submissions Gateway (ESG), the EMA eSubmission Gateway, and national competent authority portals.

Although systems such as EDC, CTMS, and ELN are commonly implemented as closed systems within life sciences organizations, their classification depends on the deployment model and access controls. When these systems are cloud-hosted and accessed by external collaborators over the internet, they may be considered open systems under 21 CFR Part 11 and may therefore require additional technical and procedural safeguards.

What Are the Key Controls for Open Systems?

When open systems are used to manage regulated records, they must comply with all applicable closed-system controls outlined in 21 CFR Part 11.10, along with additional safeguards specified in 21 CFR Part 11.30, to ensure the authenticity, integrity, and confidentiality of electronic records transmitted over uncontrolled networks.

The key controls for open systems are listed below.

• Implementation of Closed System Controls: Even when using open systems, organizations must implement all applicable controls listed in 21 CFR Part 11.10, including system validation, computer-generated audit trails, restricted user access, operational system checks, and record protection and retention safeguards. These foundational controls ensure data integrity and traceability within the broader compliance framework outlined in 21 CFR Part 11.
• Encryption of Documents: Encryption transforms electronic records into unreadable formats that can only be accessed through authorized decryption mechanisms. Encryption of documents protects data confidentiality during transmission over public or uncontrolled networks and helps ensure that only authorized users can access sensitive information.
• Use of Digital Signature Requirements: Implementing digital signatures in line with 21 CFR Part 11, including Part 11.100-11.300 as applicable, helps ensure authentication, data integrity, and non-repudiation, supporting compliance with electronic signature regulations. Digital signature mechanisms, including cryptographic methods such as Public Key Infrastructure (PKI), are commonly used in open systems to verify the signer’s identity and to ensure signed records cannot be altered without detection.

What Are the Key Differences Between Open and Closed Systems?

The key differences between open and closed systems are listed below.

1. Access Control: Closed systems limit access to authorized internal users through defined roles and permissions, while open systems may allow external access, requiring additional measures to control and monitor user activity.
2. Authentication Requirements: Closed systems rely on robust identity verification (e.g., unique user IDs, passwords, or other authentication mechanisms), whereas open systems typically require enhanced or multi-factor authentication due to external access.
3. Data Integrity Safeguards: Both system types must protect record accuracy and completeness, but open systems generally require additional controls to mitigate higher data integrity risks.
4. Encryption and Transmission: Encryption is especially critical for open systems to secure data during external storage or transmission.
5. Audit Trails: Closed systems maintain secure, computer-generated audit trails for key actions; open systems may require stricter audit trail controls to address broader access and potential external threats.
6. System Validation: Closed systems must be validated for intended use, while open systems often require more extensive validation and documented safeguards to demonstrate continued reliability and compliance.

1. Access Control

Access control ensures only authorized users can create, modify, or approve records. This protects data integrity, prevents unauthorized changes, and maintains trustworthiness during audits and inspections.

In closed systems, access is fully controlled by the organization responsible for the records and is centrally managed by administrators. Only authorized personnel are granted accounts, with actions tracked through authority checks and audit trails. In open systems, access is not directly controlled by record owners. Users of open systems may be external to the organization, and access may be managed by a third party or external system. As a result, additional safeguards such as encryption, digital signatures, and strong authentication are essential to protect electronic records.

2. Authentication Requirements

Authentication involves secure methods to verify the identity of individuals accessing or electronically signing records. Authentication ensures records and signatures are attributable to specific users, preventing repudiation, maintaining accountability, and enabling regulators to trust the authenticity of records.

In closed systems, authentication is enforced through unique user IDs, passwords, and authority checks, with audit trails linking actions to authorized individuals. In open systems, because access is not fully controlled by the organization, stronger safeguards are required. These may include multi-factor authentication (MFA) and digital signatures such as PKI to verify user identity.

3. Data Integrity Safeguards

Data integrity safeguards under 21 CFR Part 11 ensure electronic records remain accurate, complete, and reliable throughout their lifecycle. These data integrity measures ensure that records are trustworthy and protect them against alteration or loss, which is essential for audit readiness and regulatory inspections.

In closed systems, integrity is maintained through system validation, secure audit trails, retention safeguards, and controlled access, preventing unauthorized creation, modification, or deletion of records. In open systems, these controls are supplemented with additional measures such as encryption, strong authentication, and digital signature requirements to protect records during transmission or storage in less controlled environments.

4. Encryption and Transmission

Encryption and transmission involve protecting electronic records by converting data into a secure, unreadable format during storage or transfer. Encryption prevents unauthorized disclosure or tampering of records during data transmission. This ensures confidentiality, integrity, and authenticity from record creation through receipt, in line with FDA expectations.

In open systems, as records may be transmitted or stored over uncontrolled networks, encryption is mandatory. Additional safeguards, such as digital signatures and PKI, are used to verify authenticity and protect confidentiality. In closed systems, encryption is not explicitly required, as access is internally controlled. Instead, data protection relies on access controls, audit trails, and validated systems.

5. Audit Trails

Audit trails are secure, computer-generated, time-stamped records that capture the creation, modification, or deletion of electronic records without obscuring prior entries. An audit trail provides regulators with verifiable evidence of a record’s history, ensuring transparency, preventing falsification, and protecting authenticity and integrity.

In closed systems, audit trails are embedded to record all user actions and link changes to specific individuals, ensuring accountability and traceability. In open systems, audit trails must meet the same requirements as in closed systems but require additional safeguards, such as encryption and digital signatures, to prevent tampering during transmission or storage. This ensures that the audit history remains complete, accurate, and trustworthy.

6. System Validation

System validation refers to documented activities that demonstrate that electronic record systems perform accurately, reliably, and as intended. It ensures that regulators can trust electronic records and signatures as equivalents of paper records – a core requirement of Part 11 compliance.

In closed systems, validation confirms accuracy, reliability, and the ability to detect invalid or altered records through installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ) testing and ongoing re-validation following system updates. Validation also verifies that access controls, audit trails, and record retention mechanisms are functioning as intended. In open systems, the same validation principles apply, but additional safeguards are required due to external access, network vulnerabilities, and transmission over uncontrolled networks. Validation must ensure that encryption, digital signatures, strong authentication, and secure data transmission function correctly to maintain data integrity in less controlled environments.

How SimplerQMS Ensures 21 CFR Part 11 Compliance?

SimplerQMS ensures 21 CFR Part 11 compliance as it is designed to fully comply with 21 CFR Part 11 by integrating validated, cloud-based quality management tools with built-in access control, audit trails, and electronic signature functions. SimplerQMS ensures the authenticity, integrity, and confidentiality of electronic records through technical and procedural safeguards aligned with FDA 21 CFR Part 11.

Key features of SimplerQMS supporting 21 CFR Part 11 compliance include the following.

• Validated System: Delivered fully validated according to ISPE GAMP5 guidelines, with continuous re-validation for updates and upgrades.
• Secure Access Controls: Enforces 21 CFR Part 11.10(d) requirements through role-based permissions, unique user IDs, and multi-factor authentication (MFA) to ensure only authorized individuals can access the system.
• Audit Trails: Provides secure, computer-generated, time-stamped logs of all record creations, modifications, and deletions. These ensure traceability, accountability, and tamper-evidence in compliance with 21 CFR Part 11.10(e).
• Electronic Signatures: Delivers FDA-compliant e-signatures permanently linked to records, capturing signer name, date, time, and purpose aligned with 21 CFR Part 11.200.
• Data Protection: Safeguards records with encryption at rest and in transit, routine backups, and disaster recovery protocols to prevent unauthorized access or data loss.
• Training and Accountability: Verifies user competence through integrated training management before granting access. Policies for organizations will hold individuals accountable for actions performed under their unique electronic signatures.
• System Documentation Controls: Applies strict revision control and change management to all documentation, demonstrating compliance with Part 11.10(k).

SimplerQMS is a fully validated, cloud-based electronic Quality Management System (eQMS) built for full compliance with 21 CFR Part 11 requirements for electronic records and electronic signatures for life science organizations. SimplerQMS integrates core quality processes, including document control, change control, training, CAPA, audits, design control, and more into a single platform.

By embedding all necessary 21 CFR Part 11 controls, SimplerQMS helps life science companies meet stringent FDA, EU, and ISO standards, reducing compliance risks while ensuring the secure and reliable management of records and e-signatures.