Understanding FDA 21 CFR Part 11: A Guide for Life Science Developers

WTH is FDA 21 CFR Part 11? That’s a question many life science developers wanting to access the US market must have asked themselves - in one way or another.

It’s easy to be intimidated by the slew of schedules and initials you’ll be confronted with when trying to break this huge and powerful marketplace, so here’s a guide to help you understand what Part 11 really means for you.

What is FDA 21 CFR Part 11?

It’s Part 11 of Title 21 of the Code of Federal Regulations, of course.

Put simply, Part 11 sets out how a life science company operating in the US can establish an FDA-compliant, digital Quality Management System using electronic records and e-signatures in place of paper-based documentation and ‘wet signatures'.

Why does part 11 matter?

First published in 1996, Part 11  was the FDA’s (slightly belated) response to the opportunities and challenges of the information age.

As other industries were reaping the benefits of increased digitisation, pharma and medical device companies were still losing time chasing multiple real-world signatures and collating paper documents to pass FDA audits.

In Part 11, the FDA addressed the need for increased innovation in the industry’s working methods so that new products could be brought to market faster using digital tools.

However, it balanced this with the need to retain the highest level of authentication and control over approval processes for potentially lethal products.

Does 21 CFR Part 11 apply to me, then?

Almost certainly. Any developer releasing a product in the US who thinks they won’t be subject to the regulation because their ‘master copies' of documentation are all in paper form, are mistaken.

If you store or have uploaded any of your documents onto any computer system as part of your development or quality process, the regulations will almost certainly apply to you.

11 requirements for electronic record keeping in 21 CFR part 11

If you are using an electronic quality management system (eQMS) to develop your product, what controls do you need to ensure required levels of data integrity and risk management?

Sec. 11.10 outlines eleven distinct security management requirements for companies that wish to manage their electronic records using a ‘closed software system'.

What are the electronic signature requirements in FDA CFR part 11?

Part 11 outlines in detail the requirements for using electronic signatures within a closed-loop quality management system.

Signature manifest requirements

Part 11 specifies that any e-signatures applied to documents must include the printed name of the signer, the date/time the signature was applied, and the ‘meaning' or intention of the electronic signature as part of an evolving and uneditable audit trail.

Control and authentication

But rules for the application, control and authentication of these signatures are extensive:

• E-signatures must be unique to individuals
• E-signatures must be password protected (with passwords changed frequently)
• Only administrators should be able to control the use of e-signatures in the system
• Signatures must be authenticated in real-time when they are used
• An approval must always be attributable to a specific individual
• The signature cannot be removed once it is applied

If you’re putting together your own DIY eQMS with tools like One Drive and PandaDoc, you may struggle to create the most frictionless process that can work in line with the regulation.

Compliance requirements are rigorous

In trying to match the level of legal confidence offered by a 'wet signature’, Part 11 has made the authentication requirements for digital approval way more stringent. The processes you’ll need to ensure identity authentication and protection from falsification require high levels of digital document control and workflow management.

Right now, it would be significantly easier to falsify a pen and ink signature on a test result than to do the same with an electronic signature under the FDA rules!

For all these reasons, Using an eQMS's native e-signature software is the most cost-effective and reliable way to meet the regulation laid out in FDA CFR 21 Part 11.

Supporting external approvals

However, there will be times when you need a supplier outside your organisation to approve a document (for example, for equipment calibration verification or contract signing). In these cases, you will need your QMS to integrate seamlessly with a tool like DocuSign. You’ll need the facility to open up limited access to your closed system - and let your partner apply an eIDAS-compliant electronic signature where required (including date and time stamp).

Your chosen eQMS supplier should make both these routes for applying e-signatures a standard part of the package, at no extra cost to you.

But compliance makes life easier (honestly)

The good news is that implementing Part 11 will make your process more efficient. It will help you develop a compliant and paperless QMS, ultimately giving you the tools to deliver safer and more effective products in a more streamlined way.

Even so, the bar for digital compliance is set extremely high. For some, the challenge often seems too daunting, with many developers choosing to maintain their paper-based systems rather than face the upheaval of a complete digital overhaul.

The tools, processes and procedures you'll need to meet the regulation are highly exacting. It will take time to set them up and validate they're working as they should be. But once you've done so, you'll be able to collaborate more efficiently and effectively across your business and more easily demonstrate to the regulator you have built your products to the required standards.

Last updated on 04/06/2024