In December 2022, the Food and Drug Administration (FDA) published an updated version of its Validator Rules. Pinnacle 21 Principal Consultant Michael Beers delivered an overview of the differences between newly released version 1.6 and the now legacy March 2021 version 1.5.
Note: Michael Beers is a Pinnacle 21 staff member and in no way speaks for the regulatory agencies or standards development organizations. His presentation was delivered on behalf of Pinnacle 21.
We begin with Section 8 of the FDA Study Data Technical Conformance Guide, where data validation is defined as a way to help ensure that the study data are compliant, useful, and will support meaningful review and analysis at the agency.
At the agency, validation occurs at the time of submission and at the beginning of regulatory review, where submitted data is checked against various rules and standards, including:
So, where can you find the FDA Validator Rules? Navigate to the FDA website to the Study Data Standards Resources page. When expanding the section titled FDA Validator and Business Rules, you’ll find a link to download the rules.
Three new columns have been added for the addition of SENDIG 3.1.1, SENDIG-AR 1.0, and SENDIG-DART 1.1 to the FDA Data Standards Catalog. This is one of the biggest changes to the Validator Rules in version 1.6.
The other 33 rule additions were to meet a specific need; for example, medical device rules. Five of these are new SDTM rules, and another five are applicable to both SDTM and SEND. The remaining 23 new rules are for SEND only.
Note that three of the new SDTM rules have no publisher ID because there are no corresponding CDISC Conformance Rules for medical devices, and four of the SEND rules have no publisher ID because there's no corresponding CDISC Conformance Rule or FDA Business Rule.
Publisher IDs were updated for 11 rules where CDISC Conformance Rule IDs were added to existing rules. These changes affect SEND Conformance Rules 4.0 (2), SDTMIG Conformance Rules 2.0 (8), and 1 missed CDISC Conformance Rule ID that has now been corrected.
Three rules received message updates, and rule descriptions were updated for 14 more. These changes were largely housekeeping to correct typos and reformat to achieve more consistency with other rule messages and descriptions.
If you're an Enterprise user, we recommend that you always accept the latest Enterprise deployments and that you always use the latest available regulatory engines. For ongoing, in-progress studies in Enterprise, a best practice is to use the latest P21 engine, which will show you the issues for FDA, PMDA, and rules for custom standards and controlled terminology (if your company uses these). Later, when a study is finalized and approaching submission, switch to the most recent agency engine.
According to Michael Beers, when preparing to submit, “you always want to make sure that you're using the latest agency engine for FDA. You do not want to use the legacy FDA engine. This is provided just for reference.”
When you switch to the end agency-specific validation engine, such as FDA 2204.1, you’ll still see the same FDA validation issues, but you will only see the FDA issues.
If you were to use a legacy FDA engine instead of the most recent version, you would see warning messages on various screens, such as in the Data Package Details, the Submission Checklist, and even in the Validation Report. Before exporting from Enterprise, you would also see red warning messages directing you to revalidate using the latest engine.
Failure to validate with the latest engine means you won't see the exact same validation results as the agency, so don't ignore those warning messages!
If you're a Community user, the same best practice applies here. Always be sure you are using the latest version of Community and connected to the internet, and select the latest FDA engine, never the legacy engines provided strictly for reference. If you were to use an outdated engine, you would receive an “incompatible engine” warning message in the validation report.
In section 8.2.2 of the FDA Study Data Technical Conformance Guide, the FDA recommends that all Sponsors evaluate their study data before submission against the conformance rules. Here at Pinnacle 21, our mantra is that you should validate as soon – and as often – as you can.
The sooner you validate, the more likely you are to be able to fix any validation issues identified. The longer you wait to validate, fixing issues becomes more difficult due to impact on downstream deliverables.
Once you’ve validated, try to fix as many of those issues as you can. According to the FDA, “Sponsors should either correct any discrepancies between study data and the standard or the business rules or explain meaningful discrepancies in the relevant Reviewer’s Guide.”
Q. Do we need to switch to the newest validation engine if we started on a previous validation engine for an ongoing study?
A: Yes, the recommendation is always to switch to the latest agency validation engine. We understand that you may see differences from a new validation engine, but this is only good. Surfacing new issues prevents you from being surprised by FDA reviewers who have the most up-to-date version of the Validation Rules. If your team is facing time or budget constraints, you can always add an Issue Explanation to such newly flagged Issues.
It's always good to explain every issue that the agency will see in your Reviewer's Guide, even if you're unable to fix it. Sometimes the explanation is simply that the engine came out too late for you to fix, but it's best to know in advance what issues the agency will see so you know you have explanations for each.
Q. How often does the FDA plan to update their Validator Rules?
A. It appears that the goal is to publish rule updates each year. Version 1.5 was released about 18 months ago, so that can fluctuate a bit.
Q: Why isn't severity included in the FDA Validator Rules anymore?
A. This is not new to version 1.6. It was changed in a previous version of the Validator Rules. CDISC does not provide any severity for their Conformance Rules, and the FDA business rules don't have any severity either. FDA Validator Rules do not publish severity.
We have kept severity for our Enterprise clients, but we’ve changed it to “Type.” There are three values associated with Type - error, warning, and notice. Many organizations use these values as part of their validation issue management process, so we’ve maintained it for our Enterprise users.
Tags:Blog Main Page
* Required Field