In regulated laboratory environments like those of molecular diagnostics, cell and gene therapy, and manufacturing quality assurance, data integrity isn’t just a best practice, it’s a regulatory requirement. Whether you’re preparing for a regulatory inspection, supporting a regulatory submission, or maintaining ongoing compliance, how records are reviewed, approved, and signed matters just as much as the quality of the data itself.
This is where electronic signatures (eSignatures) and 21 CFR Part 11 compliance come into play.
Yet despite their importance, eSignatures are often inconsistently implemented or treated as an afterthought, potentially introducing unnecessary compliance risk. Understanding what regulators actually expect, and how modern laboratory information management systems (LIMS) should support those expectations, is critical for any lab operating in a regulated space.
“Even in labs with strong data quality practices, managing how records are reviewed, approved, and signed is often a hidden challenge. Inconsistent eSignature implementation, unclear signing roles and permissions, and incomplete audit trails can introduce risk, delay regulatory submissions, and complicate inspections. Understanding what regulators expect, and building processes that fully support those expectations, is critical to maintaining both compliance and operational efficiency.” – Brian Jack, COO of Semaphore Solutions, creators of Labbit LIMS
What Is 21 CFR Part 11?
21 CFR Part 11 is an FDA regulation that defines the criteria under which electronic records and electronic signatures are considered trustworthy, reliable, and equivalent to paper records and handwritten signatures.
In practice, Part 11 applies to any system used to create, modify, maintain, archive, retrieve, or approve electronic records that support regulated activities. This includes LIMS, LES, ELNs, and other laboratory informatics systems where data, workflows, decisions, and approvals are captured electronically.
Electronic records include any digital data generated or managed by these systems – such as results, metadata, workflows, configurations, audit trails, approvals, and changes to processes – that are required to be maintained under FDA regulations.
At a high level, the regulation focuses on three core principles:
- Authentication – Verifying that the person signing is who they claim to be
- Traceability – Ensuring actions are recorded, attributable, and auditable
- Intent and Meaning – Making clear why a signature was applied and in what role
What Is an eSignature in a Regulated Context?
In regulated environments, an eSignature is far more than a checkbox or a button click. A compliant electronic signature must be clearly attributable to a specific individual, reflect the reason for signing (such as author, reviewer, or approver), and be authenticated at the moment of signing. It must also capture the meaning and intent behind the action and be permanently recorded in an immutable audit trail.
Regulators don’t just want to see that something was signed, they want to know who signed it, in what capacity, when, and why.
Why eSignatures Are So Important for Compliance
For decades, handwritten signatures were the cornerstone of accountability in regulated laboratories. A signature on a paper record signified that a specific individual had reviewed the work, approved the results, and accepted responsibility at a defined point in time. In a paper-based world, this model worked reasonably well as records were physical, changes were visible, and signatures were inherently tied to a single, static document.
As laboratories transitioned to electronic systems, however, this model began to break down. Digital records are dynamic by nature: data can be updated, workflows span multiple systems, and many individuals may contribute to the same record over time. Simply replicating a handwritten signature – such as a checkbox or a name stamp – proved insufficient to demonstrate who did what, when they did it, and whether the record was altered after approval. This gap is what drove regulators to formalize expectations around electronic records and electronic signatures, including the requirements outlined in 21 CFR Part 11.
Modern eSignatures exist to restore and strengthen the intent behind handwritten signatures. They provide a reliable way to demonstrate that proper review and approval procedures were followed, responsibilities were clearly segregated, data was reviewed at the right time by the right personnel, and records remained unchanged after approval. When implemented correctly, eSignatures establish trust, accountability, and traceability in fully digital workflows.
When eSignatures are poorly implemented, however, labs face real and avoidable risks. Approvals can become ambiguous, audit trails may lack clarity or context, inspections can surface unexpected findings, and regulatory submissions or certifications may be delayed. In many cases, compliance challenges are not the result of flawed science, but of insufficient documentation around decision-making and approval.
As Quality Systems Now notes, “Studies show that around 60% of compliance failures start with poor documentation, underscoring that many regulatory challenges stem from insufficient record-keeping rather than flawed science.”
Modern eSignatures That Meet Compliance Expectations
To fully support 21 CFR Part 11 requirements, eSignatures in regulated labs need to go beyond simple checkboxes. They should be:
- Configurable – Not every task requires a signature and not every task requires the same type of signature. Labs need the ability to enable, disable, and adjust signing requirements as workflows evolve.
- Role-Based – Author, reviewer, and approver signatures each carry different regulatory meaning. Systems should enforce role-specific signing authority and prevent inappropriate overlaps.
- Authenticated – Signers must re-authenticate at the moment of signing to confirm identity and intent, ensuring the uniqueness of their signature.
- Contextual – Requiring a reason for signing adds intention to the signature, providing clarity for auditors and inspectors reviewing records later.
- Fully Traceable – All signature details – who, when, role, and reason – must be captured in immutable audit trails and clearly visible in the context of the work being performed.
Labbit’s eSignature framework was built from the ground up to support these compliance principles. It enables labs to define signature requirements, including which data require signatures and the reasons for signing. These requirements can be quickly configured per task or workbook, with contextual signing reasons that add clarity and intent. Users must authenticate to ensure accountability for their unique signature. Completed and pending signatures are prominently displayed on the workbook so they remain visible with the record, similar to a paper record. The full workbook lifecycle is captured in an event log, including contributor additions, signature events, reopen-for-editing actions, and workbook closure, with key signature metadata preserved as part of the event. By embedding eSignatures directly into workflows, compliance becomes a natural part of the user’s path of work, ensuring traceability, accountability, and confidence in data integrity.
"Labbit’s eSignature framework was designed in alignment with the core principles of 21 CFR Part 11, while providing the flexibility needed to support evolving, data specific signing requirements, without compromising accountability or data integrity." – Meghan Bowman, Senior Product Manager, Labbit
Why Electronic Record Architecture Matters: The Case for Graph Databases
Under FDA regulations, an electronic record is defined as any digital information created, modified, maintained, or archived by a computer system. Critically, when an electronic record is signed, 21 CFR Part 11.50 requires that the signer’s name, the date and time of signing, and the meaning of the signature be displayed in every human-readable form of that record – on screen and in print.
In many traditional systems built on relational databases, the components of an electronic record are often spread across multiple tables. Data values, metadata, workflow state, and signatures may all reside in different locations. This fragmentation makes it easy for users to view parts of a record in isolation, without the full context – including applied signatures – unless the application layer carefully reconstructs and enforces that view every time.
Graph-based data models – like the one Labbit was built on – take a fundamentally different approach. Instead of scattering record components across tables, records are represented as connected entities, with relationships such as “created by,” “modified by,” “reviewed by,” and “approved by” modeled directly alongside the data itself. Each revision of a record is treated as a complete, self-contained digital artifact, preserving both the data and its full provenance at a specific point in time.
This architectural approach aligns naturally with regulatory expectations. By keeping data, context, and signatures tightly bound, it becomes easier to ensure that electronic signatures are always displayed with the record they apply to, reducing the risk of partial views, ambiguous approvals, or missing audit context.
Compliance That Adapts as Your Lab Evolves
Regulatory compliance shouldn’t slow labs down or lock processes in place. As science evolves, workflows change and compliance systems need to adapt alongside them.
By combining configurable workflows, role-based controls, and deeply integrated audit trails, Labbit enables labs to maintain continuous compliance while still moving quickly and confidently.
In regulated environments, the goal isn’t just to pass audits, it’s to build systems that make doing the right thing the easiest thing. Properly implemented eSignatures are a foundational part of that approach.
Explore Labbit’s eSignature capabilities in this interactive tour:
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