We’d be willing to bet your key collaborators aren’t all in the same building. Your team members, contract partners, clients, and suppliers are likely scattered across the globe. That makes collecting physical, "wet ink" signatures nearly impossible and turns digital approvals into a daily necessity.
But how you collect those electronic signatures matters, especially for GxP-regulated organizations.
The typical workaround of printing, signing, scanning, and emailing creates compliance risks and breaks the digital chain of custody. A dedicated e-signature tool is the smarter move – but not all platforms are created equal. Many standard business tools simply don't meet the strict GxP compliance standards, leaving you exposed during an audit.
So how do you get it right? Here's what you need to know to make sure your e-signature process is not just efficient, but provably compliant.
The FDA is clear about what makes an electronic signature 21 CFR Part 11 compliant. It’s more than just a digital image of your name; it’s a secure process built on several layers of identity verification and data integrity.
A compliant electronic signature process must include:
The EU’s Annex 11 is usually seen as the equivalent of 21 CFR Part 11, however its guidance for electronic signatures is much shorter.
But that’s set to change. The European Commission recently released a draft of updates to Annex 11 that expands on the current guidance for electronic signatures. The heart of the guidance is the same, but the draft introduces a much more detail, seeming to better harmonize it with 21 CFR Part 11.
Some of the updates include:
The rule of thumb is straightforward: if a document and its signature touch your GxP activities, the signature must be Part 11 and Annex 11 compliant. For example, when you work with a third-party vendor on a manufacturing plan and everyone needs to approve it, those signatures require full compliance.
On the other hand, some documents like legal contracts or service agreements don't technically require this level of compliance to be valid.
However, many organizations find it’s far easier and more secure to route all signed documents through a single, compliant system. When your GxP-related approvals and your contracts are all managed in the same validated tool, you create a centralized source of truth. You never have to wonder if the right signature complies with the right regulation, and it makes finding any document during an audit much easier.
Arguably the hardest part of 21 CFR Part 11 and Annex 11 compliance is validating the eSignature tools that make compliance possible.
While your team can easily verify surface-level compliance requirements (like the presence of a name and timestamp), it's nearly impossible to validate backend functions – like ensuring a signature cannot be tampered with – without help from your software vendor.
Depending on your vendor, that could be quick and easy, or it could come with an extra unexpected cost. Some eSignature software vendors charge additional fees for access to their validation tools – but some, like ZenQMS, do not.
That’s why it’s so important to ask about the validation process and any associated fees upfront before choosing a vendor. It’s the only way to get a complete picture of cost – and of the potential stress level.
Validation isn’t a minor detail – it’s a critical part of being audit-ready. In fact, it’s not unlikely for one of the first questions an auditor will ask to be, "How do you know this signature is Part 11 compliant?". Having the validation collateral from your vendor is the only way to confidently answer that question.
Docusign and Adobe Sign are big name eSignature tools with 21 CFR Part 11 compliant options – but they come with a catch.
If you’re storing your documents in a GxP-compliant location, like an eQMS, using these tools to request and collect external signatures can create a tedious – and potentially risky – workflow. It requires you to:
This creates a disconnected process with two separate audit trails—one in your eQMS and one in the signature tool—that have to be manually reconciled during an audit. Each step introduces the potential for human error and version control issues, adding risk where it doesn't need to be.
Managing signatures – especially with external partners – shouldn’t force you to choose between compliance and convenience. That’s why we built ZenSign, a feature within ZenQMS that allows you to request and capture fully compliant electronic signatures from anyone, anywhere.
ZenSign is designed to streamline the collection of a single, global signature from one or more users on an entire document. This is perfect for when you need a contractor to approve a manufacturing plan or a vendor to sign off on a waiver.
Here’s how it simplifies your workflow while tightening your compliance:
Ultimately, ZenSign helps you enforce compliant workflows for your critical GxP documents while offering a centralized, easy-to-manage platform for all your signature needs.
Navigating the 21 CFR Part 11 compliant eSignature vendor selection process can be complex – but coming equipped with the right questions can help.
This guide provides 10 essential questions designed to cut through marketing claims and get to the heart of what matters for GxP-compliant signatures. Use them to vet potential vendors, uncover hidden fees, and select a partner who will truly support your compliance goals, not complicate them.