IMDRF Explains How to Build Submissions Using its Table of Contents Structure

The International Medical Device Regulators Forum (IMDRF) issued a final assembly and technical guide on building submissions using the IMDRF Table of Contents (ToC) structure, including harmonized technical guidelines on the acceptable folder structure and file format(s) for ToC-based submissions.

The final guide was posted on Wednesday after IMDRF convened in Moscow—Russian regulators are currently chairing IMDRF—for a three-day open stakeholders forum that kicked off on Tuesday. The new document sets forth new guidelines for how to build ToC-based submissions for the six IMDRF regions participating in the ToC program. It was first proposed by the regulated product submissions ToC working group in March 2015.

A sponsor can use the ToC pathway to submit applications or submissions simultaneously or sequentially to the participating regulatory authorities, which currently include the US Food and Drug Administration (FDA), Health Canada, Australia’s Therapeutic Goods Administration (TGA), Brazil’s ANVISA, the China National Medical Products Administration as well as the EU’s notified bodies. Adoption of the ToC program has differed across the IMDRF regions, with Canada being the only region currently requiring its use.

In the US, sponsors submitting a 510(k) or a premarket approval (PMA) application to either the Office of Device Evaluation or the Office of In Vitro Diagnostics and Radiological Health within FDA’s Center for Devices and Radiological (CDRH) and to another participating IMDRF regulator can choose to participate.

The IMDRF ToC program is intended to reduce regulatory burden and achieve cost savings by enabling device sponsors to satisfy regulatory requirements on premarket submissions or applications across the participating jurisdictions. “The ToC has been developed with flexibility to allow for use of the same structure across a variety of risk classes,” IMDRF said in the final assembly and technical guide.

The finalized assembly and technical guide is largely similar to the draft version from September 2015. It lists the five IMDRF documents that are required to build a ToC-based submission. These include the set of final documents for marketing clearances of in vitro diagnostic (IVD) medical devices and non-IVD medical devices from March 2018, the additional regional guidance that some of the participating regulators first issued about four years ago and the final assembly and technical guide, among others.

A new appendix on “helpful hints” was added to the draft version of the assembly and technical guide.

“As the ToC documents are comprehensive in nature, not all headings are required for all submission types and/or jurisdictions,” IMDRF said. “The ToC documents are therefore intended to work together with a separate document created for each participating jurisdiction—a Classification Matrix.” In addition to classification matrices, the appendix also addresses overview folders and custom headings as well as statements of “not applicable” and the two quality management system chapters in the ToC.

Except for Canada, other regions have yet to demonstrate interest in mandating use of the IMDRF ToC structure. But several IMDRF countries have reportedly expressed interest in a new program, deemed the Medical Device Single Review Program (MDSRP), that would use the ToC structure as its foundation or an updated version of the ToC structure that was just finalized last March. The first final versions of the ToC structure were introduced about five years ago in two IMDRF technical documents by then IMDRF chair and current CDRH Director Jeff Shuren, a major promoter of MDSRP.