FDA’s New Business Rules Explained

July 5, 2017

Pinnacle 21 recently hosted a webinar discussing the FDA’s new business rules for clinical data. You can watch the video, access the slides and review the Q&A list.

Webinar Video

On March 14, 2017, the FDA published new business rules to support the meaningful regulatory review and analysis of study data. The rules apply to SDTM formatted clinical studies and SEND formatted non-clinical studies.  The rules are the result of a multi-year effort:

  • In November 2014, the FDA published validation rules for SDTM and SEND.
  • A year later, the PMDA published their validation rules, including ADaM and define.xml. These are the rules that are in production today at both agencies.
  • In October 2016, the FDA published the Study Data Technical Conformance Guide v3.2 and the Technical Rejection Criteria in expectation of the December 17, 2016 deadline for using standards in the data standards catalog for electronic data submissions.
  • In January 2017, CDISC published the SDTMIG v3.2 conformance rules.

The Study Data Technical Conformance Guide v3.2 introduced three types of validation rules:

  1. Technical Rejection Criteria
  2. Standards Conformance Rules
  3. FDA Business Rules

(Check out the Validation Rules Browser on Pinnacle 21’s website to see the list of cross-agency validation rules and versions of Pinnacle 21 in which they have been implemented.)

Technical Rejection Criteria

We see the Technical Rejection Criteria as the first step in enforcing the December 17th deadline for Study Data Standards Guidance. These criteria were added to existing eCTD validation criteria and the agency has not specified when they are effective. However, they promised a 30-day notice for updates. There are only two rules so far and both are currently implemented in Pinnacle 21.

  • Rule #1734 requires that Trial Summary (TS) dataset must be present for each study in Module 4 and 5
  • Rule #1736 requires that a Demographic (DM) dataset and define.xml must be submitted in Module 4 for nonclinical data AND that DM dataset, Subject level analysis dataset (ADSL) and define.xml must be submitted in Module 5 for clinical data

The FDA conducted a recent analysis of applications received since the December 17th deadline and found that 45% of applications would have been rejected based on these rules if they were enforced today.

Standards Conformance Rules

Standards Conformance Rules will no longer be published by the FDA. The CDISC teams will take responsibility for updating them.

SDTMIG v3.2 Conformance Rules were published in January 2017.

  • There are 410 rules where 325 are programmable and can be implemented as an automated check.
  • 85 are conditional, meaning that they may be programmable based on conditional factors.
  • The Pinnacle 21 team has determined that 17 of the conditional rules are actually programmable for FDA and PMDA.

After evaluating the SDTMIG Conformance Rules, Pinnacle 21 concluded that we already address 212 of the 325 programmable rules. 104 of the rules still need to be implemented and 9 need clarification because of conflicts with FDA business rules or misclassifications.

ADaMIG v1.0 Conformance Rules were published September 20, 2010 and updated on January 20, 2015. Read our blog post on how Pinnacle 21’s implements ADaM validation checks.

FDA Business Rules

The FDA Business Rules were developed to reinforce internal business processes and help to ensure that the study data is useful and supports a meaningful review and analysis. These rules complement the Technical Rejection Criteria and Standards Conformance Rules and supersede previously published validation rules.

There are 45 business rules for clinical data and 41 business rules for non-clinical data. These are available for download from the FDA website.

The Business Rules are accompanied by Validator Rules that describe the implementation of the business rules in DataFit, the agency’s instance of Pinnacle 21 Enterprise. The Validator Rules were published for transparency purposes. There are 115 Validator Rules for clinical data with the rules for non-clinical data coming soon. Savvy users will notice that the rules no longer list a severity. This is intentional. The FDA will no longer publish severity because there was confusion on the topic and many sponsors were ignoring Warnings. Now, all rules with the exception of Technical Rejection Criteria, are considered equal.

What You Can Expect from Pinnacle 21

We are working on implementing the final rules for SDTMIG v3.2 and ADaMIG v1.1. Concurrently, we are also working on implementing the draft rules for Define.xml v2.1 and SENDIG v3.1. We continue to work with FDA, PMDA and CDISC to clarify and resolve remaining conflicts in the rule sets and will be launching a public BETA in August. We are asking for your participation in the BETA so we can include your feedback in the production release that is currently scheduled for November.

You will also see more educational materials including white papers, blogs and training on “Good Data Validation Practices”. In this effort, we’ll share best practices for performing data validations, interpreting validation results, evaluating risk of data issues, fixing data errors and explaining data issues.

What You Can Expect from FDA

We expect to see updated Validator Rules from SENDIG v3.0. As the agency gains valuable experience with standardized data, we also expect them to update the rules to reflect this experience and their cross-center collaboration. We would expect the FDA to continue to clarify existing rules and correct issues and inconsistencies that have been identified so far.

What You Can Expect from PMDA

We expect that the PMDA will publish a new release of validation rules that incorporates the new SDTMIG v3.2 and ADaM v1.1 rules, FDA Business Rules and learnings from their own pilot experiences.

Important Notes
Pinnacle 21 Enterprise Users: We hope that you will provide feedback in our BETA program and learn, participate in and support our Good Data Validation Practices.

Pinnacle 21 Community Users: Be sure to upgrade your environment to agency compatible versions (FDA – 2.2.0 and PMDA – 2.1.3 or above). Our current user metrics indicate:

  • 59% of US and EU users are currently NOT compatible with FDA
  • 17% of Japanese users are not compatible with PMDA
  • 68.3% of users have not configured MedDRA
  • 99.8% of users have not configured SNOMED

Common compatibility issues for Pinnacle 21 Community users include using older versions of Community, not configuring MedDRA and SNOMED, customizing rule configurations or CDISC CT files and running validations on a server or shared environment.


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