The FDA has stringent regulations that apply to life science companies, particularly when it comes to electronic records and signatures. One essential part of complying with those regulations is filing a 21 CFR Part 11 letter of certification, better known as a letter of non-repudiation agreement. For those unsure of what these letters do, how to write one, and other details, this guide lays out what you should know. You can also download the whitepaper “How to Prepare for a 21 CFR Part 11 FDA Inspection“.

What is a 21 CFR Part 11 Letter of Certification?

As part of the compliance process, all life science companies must file what’s called a letter of non-repudiation agreement with the FDA. This letter must be on file with the organization, or the organization will deem you not in compliance.

According to the FDA’s website, “A letter of Non-Repudiation Agreement for digital signatures must be submitted to the FDA prior to registering as a transaction partner for the FDA ESG. The letter must be submitted (preferably on company letterhead) and signed with a traditional handwritten signature. Users requesting a new ESG account must send an electronic copy of their Letter of Non-Repudiation to ESGHelpDesk@fda.hhs.gov. In addition, users must send a physical copy to the FDA. Users must send a hard copy within 2 weeks, or your account may be disabled.”

Where Should You Send a 21 CFR Part 11 Letter of Certification?

According to the FDA, all letters of non-repudiation agreement should be sent to the following address:

Lowell Marshall
Electronic Submissions Gateway
U.S. Food and Drug Administration
3WFN, Room 7C34
12225 Wilkins Avenue
Rockville, MD 20852

What Should a 21 CFR Part 11 Letter of Certification Look Like?

The FDA has provided two sample letters on the organization’s official government website. Both include placeholders in brackets that indicate where you should supply information, as well as what information is needed. You can find the two sample letters of non-repudiation agreement here: https://www.fda.gov/industry/about-esg/appendix-g-letters-non-repudiation-agreement

We have also included the text of both sample letters below for your convenience:

SAMPLE LETTER #1

[Company Letterhead]

[Today’s Date]

Lowell Marshall
Electronic Submissions Gateway
U.S. Food and Drug Administration
3WFN, Room 7C34
12225 Wilkins Avenue
Rockville, MD 20852

Re: Electronic Signatures

Dear Sir or Madam:

Pursuant to Section 11.100 of Title 21 of the Code of Federal Regulations, this is to certify that [Company Name], [Company Address], intends that electronic signatures executed by our employees, [List of employee names] are the legally binding equivalent of traditional hand-written signatures.

Sincerely yours,

[Hand-written signature]

[Company Representative Title]

[Employee Name #1]: _________ [Hand-written signature of employee #1]

[Employee Name #2]: _________ [Hand-written signature of employee #2]

[Employee Name #3]: _________ [Hand-written signature of employee #3]

[etc.]

SAMPLE LETTER #2

[Company Letterhead]

[Today’s Date]

Lowell Marshall
Electronic Submissions Gateway
U.S. Food and Drug Administration
3WFN, Room 7C34
12225 Wilkins Avenue
Rockville, MD 20852

Re: Electronic Signature Certificate Statement

To Whom It May Concern:

Pursuant to Section 11.100 of Title 21 of the Code of Federal Regulations, this is to certify that [Company Name] intends that all electronic signatures executed by our employees, agents, or representatives located anywhere in the world are the legally binding equivalent of traditional hand-written signatures.

Sincerely yours,

[Hand-written signature]

[Name of Company Representative]
[Company Representative Title]

Does 21 CFR Part 11 Apply to Me?

For those who are unsure whether the rules and regulations apply to their organizations, answer the following four questions:

• Is there another FDA requirement to maintain records (a predicate rule)?
• Do you choose to meet that requirement by keeping electronic records?
• Do you use electronic signatures to document that specific things (actions/events) have occurred?
• Do you submit electronic records to the FDA?

If you answered yes to the above, then 21 CFR Part 11 does apply to you, and you’ll need to complete and mail a letter of non-repudiation agreement to be on file with the FDA. If you are still unsure, take the GAMP Approach to 21 CFR Part 11 Compliance course to help you navigate the FDA’s compliance landscape.

What Happens If You Don’t File a 21 CFR Part 11 Letter of Certification?

If you fail to file a letter of non-repudiation with the FDA, you’ll be deemed out of compliance, even if you’ve followed every other step required of you. That could lead to receiving Form 483, as well as FDA warning letters. If the situation is not corrected, you could see damage to your organization’s reputation and potentially lost business, as well as further action from the FDA. Thankfully, filing a letter of non-repudiation is simple and takes very little time.

Why Do I Need to File a Letter of Certification?

Filing a letter of certification with the FDA signals that your organization complies with the requirements laid out in 21 CFR Part 11. It also shows that you have followed all the steps required of you, including:

• Software/system validation
• Creating validation records for system installation and release
• Developing user training records
• Conducting due diligence when it comes to vendor validation (if applicable)
• Developing internal SOPs and policies

eLeaP has over 18 years of experience helping life sciences organizations comply with the FDA’s rigorous 21 CFR Part 11 auditing and inspection process. Get a free consult or start a free sandbox account to see how the system works.

The Role of Your Learning Management System

While an LMS might not help you create and file a 21 CFR Part 11 letter of certification, it does play a critical role in your compliance. Creating training plans for employees and ensuring that everyone completes modules covering topics related to password hygiene, software system use, electronic signatures, accountability and responsibility, and data protection are central parts of complying with the FDA’s rules.

The right LMS is vital – as an electronic system, it, too, must be validated and compliant with the regulations. At eLeaP, we designed our learning management system to deliver best-of-breed capabilities but also to comply with 21 CFR Part 11 rules. It is fully validated and fit for use. Contact us today to learn more or to schedule your custom consultation.