On August 21, Health Canada announced that they would be adopting the IMDRF “ToC” format for medical device market authorisation requests. As of April 1, 2019, Premarket Applications for Class III and IV devices (which aren’t the same classification as FDA’s Center for Devices and Radiological Health) will need to be in this format, and not the current “STED” format.
The “ToC” format comes from the International Medical Device Regulators Forum’s (IMDRF) Regulated Product Submission group, which participated in the development of the Health Level 7 (HL7) RPS standard that has also been designated for use as the eCTD version 4 (for pharmaceutical products). This produced a moment of panic: Could Health Canada have leapfrogged FDA and the ICH efforts for implementing an RPS-based submission format? The implementation documentation at IMDRF (search on that page for RPS, there’s a number of documents) suspiciously did not mention anything about XML or controlled vocabularies, and a quick note to Nancy Shadeed at Health Canada confirmed that:
Health Canada just announced that they will be adopting the ToC structure as an option for submitting premarket submissions. These will be accepted in a non-RPS format. However we are not adopting the RPS yet for medical device submissions as we have not yet established an IMDRF implementation guide along with controlled vocabularies… along with the necessary documentation that is needed to be provided to tool vendors.
Because medical devices are rather different from pharmaceutical products, and the approval of devices is a quite different process in different parts of the world from drug market approvals, the content of the ToC fomat (as well as the older STED format) has a very different list of required documents. Compared to the ICH Common Technical Document’s (CTD) 5 sections (Regional, Summary, Quality, Safety, Efficacy), the IMDRF ToC has seven sections.
- Chapter 1: Regional Administrative – this contains Cover letter, application form, etc., but not regional-specific information that is the subject of the other chapters below.
- Chapter 2: Submission Context – this contains the device description, references to similar/previous versions, indications, and development and market history.
- Chapter 3: For devices which are not in-vitro diagnostics, this contains Non-Clinical Evidence, similar in concept to the CTD’s Module 4 but also covering subjects such as electrical safety and software that wouldn’t be in a drug’s list of concerns. For In Vitro Diagnostics, this section contains Analytical Performance and Other Evidence including risk management, standards, stability, and analytical reports.
- Chapter 4: Clinical Evidence – this covers human safety and efficacy
- Chapter 5: Labeling and Promotional Material – this is material that is in the CTD’s regional section, but the IMDRF ToC aligns the internationally common document categories.
- Chapter 6A: Quality Management System Procedures – for devices, the manufacturing quality is a key part of the approval, and is considered a major section. This section covers the Quality System of the company
- Chapter 6B: Quality Management System Device Specific Information – this covers how the system in the previous chapter was implemented for this particular device, including analysis and quality monitoring
As hinted above, The IMDRF ToC finds all the international common points, and puts any regional-specific items in the same hierarchy. Most sub-headings in the specifications have separate or shared slots for US FDA, EU, Health Canada, ANVISA, TGA, etc. documents. This should make it easier to build a global dossier with everything needed worldwide, then ‘trim it back’ to just what is needed for each agency. Each heading level specifies the folder and file name of the documents to go in that spot, for electronic submissions.
The documentation on the In Vitro and Non In Vitro tables of contents detail all the documents needed to assemble a market application. IMDRF has not yet settled on a common format for clinical/investigational applications, or for simpler, safer devices that typically use a premarket notification such as the US FDA 510K process. However, if you look at the list of documents it provides some hints at how this will be used when the RPS standard is adopted – the document heading numbers are in the format that IMDRF used during testing of the RPS standard during development at HL7. However, there are plenty of unknowns, such as the vocabularies for keywords (what’s called Metadata in the eCTD world), and whether IMDRF will use features of the RPS standard that aren’t being implemented for eCTD, such as document-level (as opposed to table of contents-level) keywords, and hierarchical documents. For now, though, the electronic format will be more similar to what’s called NeeS (Non-eCTD Electronic Submissions) for drug submissions. Note that the specifications do not specify folder and filenames, although it seems likely that Health Canada will make that part of their implementation guide.
The Publishing module in ARIM 3.3 can create submissions in the IMDRF ToC format as a paper-style publication. ACUTA (an IQVIA company) will be adding the necessary features to permit the use of electronic submissions with the correct folder structure required by the IMDRF specifications in a future release – mainly new submission templates – as a first priority for Med Tech support.
Please contact us for more information on how we can assist you with your medical device or biopharmaceutical regulatory requirements.