April 25, 2023
By Sarah Fitzgerald and Evangeline Loh
The International Medical Device Regulators Forum (IMDRF) has reported significant progress regarding development of a harmonized regulatory submission format for multiple medical device markets and jurisdictions.
The IMDRF represents some of the world’s most advanced and largest medical device regulatory agencies, including Brazil, China, the European Union (EU), Japan, South Korea, the US and the World Health Organisation (WHO).
The IMDRF’s Regulated Product Submission (RPS), developed over the course of a decade, had been endorsed as a program since the forum’s inaugural meeting (March 2012, Singapore). The IMDRF recognized it was pivotal to work on a harmonized submission format and a method for global electronic submissions. In 2019, the regulators acknowledged the reality that “it may be a long-term effort to implement harmonized electronic submissions as common practice.”
RPS as a New Work Item
The RPS working group (WG) has continued to make progress and announce its achievements. The charter of the RPS WG is to “build on the common Table of Contents (ToC) for medical device regulatory submissions and create a dynamic template that supports the electronic transmission of regulatory submissions.”
Progress of the RPS working group
There were many updates from the RPS WG reported at the various IMDRF meetings. One particularly informative synopsis was presented by Health Canada during the Brasilia March 2016 IMDRF meeting, which describes the group’s implementation and governance.
Harmonized Table of Contents
It was recognized that a harmonized Table of Contents (ToC) would be the first element needed for development of harmonized global electronic submissions. The IMDRF ToC is viewed as a global “comprehensive submission structure” that also guides the “location of submission elements.” The first version of this harmonized structure ToC document (PD1) was released in February 2013 for both medical devices (“non-in vitro” nIVD, IMDRF/RPS WG/N9) and in vitro diagnostic (IVD) devices (IMDRF/RPS WG/N13) .
The ToC was piloted (Plan IMDRF/RPS WG/N26) from October 2015 to December 2017. The March 2016 update indicated that 22 requests had been received, and at the time, 11 accepted. An IMDRF RPS Communication (January 2019) described the following: 17 devices were formally in the pilot and 15 applications had been approved.
The ToC guidance documents have been revised and released three times: R1 (May 2014), R2 ( March 2018), and R3 (March 2019). There is a current revision (R4) under public consultation since mid-February 2023. In addition to the ToC guidance, IMDRF has published other documents issued to guide manufacturers, as have several of the individual regulatory agencies.
Health Level Seven
In July 2015, the RPS WG announced the Health Level Seven (HL7) RPS Standard. HL7 was established as “ "fit for purpose" for the electronic exchange of information related to premarket medical device applications.” The RPS WG presented their assessment of the technical format options at the September 2015 Kyoto IMDRF meeting. The RPS WG recommended that the HL7 RPS XML Messaging Standard be adopted as the “as the future electronic information exchange format to be used for medical device submissions.” The IMDRF Management Committee (MC) agreed to profile the Strategic Assessment of Electronic Submission Messaging Formats (October 2015 IMDRF/RPS WG/N32) and the ToC pilot as well as for efforts to continue towards RPS as the future electronic information exchange format for medical device submissions.
The HL7 RPS standard was tested twice to assess whether it was sufficient for “electronic exchange of information related for premarket medical device applications.” (See RPS Beta Test document (May 2014, IMDRF/RPS WG/N21) and RPS Beta Test Round 2 document (July 2018, IMDRF/RPS WG/N50)).
Significant Progress after 2020?
At the Singapore IMDRF meeting (September 2020), the RPS WG (Health Canada) provided an update. Health Canada posted the ToC guidance in April 2019, and to September 2020 reported that 30% of Medical Device Licenses (MDL) submitted were in the IMDRF ToC format. The WG also shared that the US Food and Drug Administration (FDA) had been developing a medical device submission assembly tool.
None of the FDA official announcements about the electronic Submission Template And Resource (eSTAR) stated that it was intended to align w/the IMDRF. eSTAR is an “interactive PDF form” which purports to benefit applicants as it guides the user through the application and compilation process: automation, resources provided (guidances, FDA databases), and verification. In addition to the benefits to the application, the content and structure are aligned with the FDA’s Center for Devices and Radiological Health (CDRH) review documents.
This all began in September 2018 with the Quality in 510(k) Review Program and eSubmitter. In February 2020, the FDA developed and launched eSTAR. The pilot commenced in June 2022. eSTAR is currently voluntary.
As of now, eSTAR is expected to be compulsory starting October 1, 2023. The current version of the eSTAR templates are provided on the FDA website.
IMDRF and eSTAR, and now Health Canada
At the South Korea IMDRF meeting (March 2021), the RPS WG reported on the FDA and eSTAR. It was announced that the FDA intended to harmonize eSTAR completely with the IMDRF ToC structure. In addition, collaboration between the FDA and Health Canada on eSTAR included Canada piloting eSTAR for Class III and Class IV MDLs.
The official Health Canada eSTAR pilot was announced for a limited number of certain medical device types in January 2023.
What was reported at the March 2023 IMDRF meeting?
The RPS WG intends to transform the ToC updates into the eSTAR template, as it is currently programmed with FDA and Health Canada submission requirements. There is progress with this global electronic submission template, and for now it appears to be based on eSTAR.
Of course, global harmonization excites us all. And, global submission harmonization is fantastic. One comment, is that the eSTAR template appears to be developed using Adobe Acrobat’s “XFA Forms," which were commonly used to create interactive, dynamic and fillable PDF forms. However, this technology has since been deprecated by Adobe in 2017, making any programmatic manipulation of the eSTAR template challenging . Also, full access to all of the features of the eSTAR template requires upgrading to Adobe Acrobat Pro (or a suitable equivalent such as Foxit PDF Editor Pro).
We will continue to monitor. (Read our other Insights on the IMDRF, Essential Principles and leveraging authorizations.)
Sarah Fitzgerald is Senior Consultant, Quality and Regulatory affairs and Evangeline Loh is Global Manager, Regulatory Affairs at Emergo by UL.
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