On December 15th, 2021, the Japanese Pharmaceutical and Medical Devices Agency (PMDA) published its long-awaited update to the Validation Rules for SDTM, ADAM and Define-XML. PMDA Validation Rules 3.0, aka PMDA Engine 2010.2, introduced additional standard conformance rules from CDISC, support for ADaM-IG 1.1, and many other changes.
Seiko Yamazaki, authorized CDISC ADaM trainer and Pinnacle 21 Consultant, took us through what you need to know about this update in our recent webinar. Below are some additional key points, as well as answers to related questions from our attendees.
The PMDA performs independent validation of your study data in their P21 Enterprise environment and reconciles their results with the results and Explanations of the sponsor. Using the same Engine that the PMDA will use is the best way to de-risk the review process. Discrepancies can cause delays in the submission and approval timeline, or even rejection.
Q: Can I use different PMDA Engine versions, such as Legacy Engines, for different studies in the same application? When will PMDA Legacy Engines be deprecated?
A: The PMDA allows only one Engine version (i.e., Validation Rules version) to be selected per application.
As of as of 2021-Q4, we deployed PMDA Engine 2010.2 to the PMDA and to the users of P21 Community and Enterprise. We covered the main highlights previously in our blog post: P21 Releases New PMDA Validation Engine.
Q: How can I access PMDA Engine 2010.2? It is released to general availability?
A: Yes, it is now released to general availability. Explore it in all P21 products:
Q: Which Validation Rules changed in PMDA Engine 2010.2, especially those related to ADaM-IG 1.1?
A: The PMDA has published this information: Study Data Validation Rules Version 3.0. The biggest changes are the 8 new Rules for ADaM-IG 1.0 and 253 new Rules for ADaM-IG 1.1. The chart below provides a breakdown of new rules, removed rules, algorithm changes, and more.
Q: In P21 Enterprise, is the P21 Engine simply the latest PMDA and FDA Engines combined?
A: Yes and no. The P21 Engine aims to be a superset of the most recent Validation Rules, regardless of agency.
If Issues with Severity of Reject are found in your validation results, the PMDA's review will be suspended until the Issues are fixed. The PMDA’s review will also be suspended if corrupt files cause the validation itself to fail.
Q: Our submission to the PMDA includes an older study that is showing Reject Issues? Should we submit it as is?
A: No, if you are including older studies in your submission package, all Reject Issues need to be fixed. The same applies to newer studies, too. If you do not fix Reject Issues, there is a high risk of automatic rejection by the PMDA.
Q: In our pre-submission consultation with the PMDA, do we need only the P21 Validation Report with our Explanations for Issues with Severity of Error, or do we need to prepare our complete data package, including XPT files, define.xml, and the Reviewer’s Guide?
A: The latter. To resolve key Reject and Error Issues, you need to prepare and validate a complete data package that includes the needed supporting documents, such as define.xml, the Reviewer’s Guide, and Form A.
The PMDA submission process is very different from that of the FDA. While both regulatory agencies require validation and Explanations for unfixed Issues, the PMDA instructs that Issues with a Severity of Error that cannot be fixed need to be disclosed to the PMDA via Form A for Explanation of Error Issues at the Pre-NDA meeting. The PMDA presented a process overview in Feb. 2022 (Japanese language only).
Q: Why does the PMDA maintain the Severity category, while the FDA does not?
A: The PMDA still maintains and publishes the Severity category to support their Issue triage and inquiry process. However, the FDA has deprecated Severity altogether, apart from Reject, and now simply requires every unfixed Issue to have an Explanation.
Q: If our data package complies with the FDA’s submission requirements, can we reuse that package as is for the PMDA as well?
A: Not necessarily. The agencies don’t have exactly the same requirements. For example:
Q: For PMDA submissions, do we need to remove items relating to the SNOMED dictionary from our Trial Summary (TS) domains?
A: No, you may keep items relating to the SNOMED Controlled Terminology (CT) intact, and the PMDA will simply ignore them. Japan is currently not a member country, and thus the PMDA does not deploy that dictionary or run Validation Rules related to it.
The PMDA’s Technical Conformance Guide and the Q&A on the PDMA website have details on handling language encoding. As a rule, submit to the PMDA datasets consisting of alphanumeric characters only.
Q: If our SDTM datasets include double byte characters, should we correct them?
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