The devil is in the details: a deep dive into the state of Notified Body designations

Quick background on the European medical device and diagnostics regulations and Notified Bodies designation

• Though the European medical device and diagnostics regulations came into force seven years ago, regulators haven’t yet achieved the same number of designated Notified Bodies (NBs) as under the previous medical device and IVD directives. Of the three directives (active implantable medical devices (AIMDD; Directive 90/385/EEC)), medical devices (MDD; Directive 93/42/EEC) and IVDs (IVDD; Directive 98/79/EC)), 10 Notified Bodies still have active implantable designation (all of whom also have MDD designation), 50 retain medical device designation and 19 still have IVD designation. Notably, all of the NBs with AIMDD designation also have MDD designation. Europe replaced the three directives with two regulations – the medical device regulation (MDR; Regulation (EU) 2017/745) encompasses active implantable and general medical devices; diagnostics, including companion diagnostics are governed a separate IVD regulation (IVDR; Regulation (EU) 2017746).
• And the new regulations are more burdensome in many ways. It’s more arduous and more difficult for prospective Notified Bodies, or conformity assessment bodies (CABs), to be designated by their qualified Member State competent authorities, with some designations taking more than two years. Manufacturers need to produce more data, generate more in-depth technical and clinical testing and documentation, and do more benefit-risk analysis than was required under the directives. The regulations increase focus on post-market requirements and expect continuous and instantaneous updates to all reports and documents when either the product or the benefit-risk ratio changes. This means that not only do sponsors have to meet a higher bar, but Notified Bodies have more to evaluate and are working to a higher safety standard, as well as the new standard of whether a device or technology is “state of the art.”
• Notified Body designation is a multi-step process dependent on multiple groups. As described in the guidance MDCG 2022-13, a CAB submits an application for designation, which is reviewed by national regulators, the Medical Device Coordination Group (MDCG) and the Commission, who create a joint assessment team (JAT) to review the CAB. The JAT reviews the complete application and conducts an on-site audit, and the CAB responds to audit findings with a corrective and preventive action (CAPA) plan. The national designating authority reviews the plan and either sends the plan back as inadequate or completes a final assessment report, if all actions have been completed satisfactorily. The Commission, MDCG and JAT review the report and issue a final opinion and a draft designation. [ Read this AgencyIQ analysis for a complete description of the process.]
• And more IVDs need Notified Bodies now. Under the IVDD, very few IVDs required Notified Body intervention, while under the IVDR, nearly all do. One estimate, from the Netherlands’ National Institute for Public Health and the Environment, noted that around 7% of IVDs required NB intervention under the IVDD, but 12 times that number, or 84%, will require it under the IVDR. The other challenge is that, because most IVDs didn’t require NB involvement before, those manufacturers wouldn’t have had their technical documentation reviewed by an external party, so their technical documentation may not be up to NB expected standards.
• Competent authorities may limit the scope of designation of a given Notified Body based on the knowledge, experience and training of the personnel employed by the NB, confirmed during the designation process. The competent authorities devised a coding system to describe the depth and breadth of the designation scope.
• Under the directives, the NBOG group defined designation codes. The Notified Body Operations Group (NBOG) published a best practice guide in 2009 that defined the scope of designation for a Notified Body under all three medical product directives. This guide outlined the NANDO codes that describe the depth and breadth of a Notified Body’s designation. MD 0100 series codes describe all non-active, non-implantable medical devices, MD 0200 describe non-active implants, MD 0300 devices for wound care, and MD 0400 non-active dental devices. Active medical devices fall into these categories: MD 1100 general active medical devices, MD 1200 devices for imaging, MD 1300 monitoring devices, MD 1400 devices for radiation and thermo therapy. Series AIMD 0100 describes all active implantable device types. Finally, IVDs fall under either List A (series IVD 0100 and 0200), List B (series IVD 0300), or devices for self-testing (series IVD 0400). The directives also had special scopes describing, for example, devices incorporating drugs, IVDs and medical devices in sterile condition, etc. These comprise the MDS series (MDS 7000, 7200). The most current scope expressions (MD and MDS codes) are found in three NBOG forms: NBOG F 2012-1 (medical devices), NBOG F 2012-2 (active implantable medical devices), and NBOG F 2012-3 (IVDs).
• Under the new regulations, the Commission modified and updated the codes used to describe the scope of designation. First described in an implementing regulation and examples provided in two MDCG guidance documents, these codes cover “various device types which can be characterized by design and intended purpose, manufacturing process and technologies used, such as sterilization and the use of nanomaterials.” For medical devices, MDA and MDN codes describe design and intended purpose for implantable and non-implantable medical devices, respectively, and MDS and MDT codes describe particular characteristics, technologies and processes; there are 71 MDR codes in total. Similarly, for IVDs, IVR codes outline design and intended purpose, IVS codes are for specific device characteristics, IVT for technologies, IVP for knowledge required for examination procedures, and IVD codes for needed knowledge in laboratory and clinical disciplines; there are 80 IVDR codes in total.

What is the state of Notified Body designations 7 years after the MDR and IVDR have entered into force?

• How many Notified Bodies remain designated to the previous directives? The NANDO database provides information not merely on which Notified Bodies are currently designated to what legislation, but how many certificates have expired, or been withdrawn or suspended. According to the NANDO database, there are many more withdrawn and expired certificates than active ones, though the totals don’t reflect the highest number active at once. For MDD, that number was once as high as 80, and IVDD had 22 active designations at one time.

Table 1: Directives designation numbers show more withdrawn or expired Notified Body designations than are currently active

• How many have been designated to the regulations to date? The earliest a Notified Body could be designated to the MDR and IVDR was November 2017, according to MDR Article 123 and IVDR Article 113. The first MDR designation occurred in May 2019, for the Notified Body TÜV SÜD (actually, BSI UK received the first designation in April 2019 but had to withdraw its designation upon Brexit in early 2020). DEKRA received the first IVDR designation in October 2019. Since then, regulators have designated a total of 49 Notified Bodies under MDR and 12 under IVDR. Figure 1 shows the designations by year since 2017 and through June 4, 2024.

• Are there any still awaiting designation to the regulations? There are a handful. The Commission periodically publishes the status of CABs that applied for MDR/IVDR designation and where they are in the process of becoming designated Notified Bodies. The report lists the number of CABs at each of the ten stages of conformity assessment – application for designation, preliminary assessment report (PAR), completion of on-site joint assessment, CAPA received, CAPA review, final report, final opinion, MDCG recommendation, designation and NANDO entry. The Commission’s chart shows the total applications and how many of those have received designations (Figure 2).

Figure 2 comes directly from the Commission report referenced above and shows how many Notified Bodies have progressed through the 10 designation stages. Per that chart, 13 CABs are still working on MDR certification and 10 on IVDR certification. But what is somewhat obscured in those data are how many Notified Bodies sit at each stage of designation. Table 2 shows that information:

• The CABs still awaiting designation are all at an early stage in the designation process. Per Table 2, there are no CABs in the final five stages. There are still five CABs in the very first phase – submitting an application. There is one at the preliminary assessment phase and 10 in the on-site audit phase. Seven are in the two CAPA phases.

Table 2: CABs remaining at each stage of designation

Details about the scope of designation

• Here, we’ll talk only about MDR designations, as IVDR designations generally cover most IVDR codes.
• Codes cover by 25 Notified Bodies or fewer: The designation codes with the fewest Notified Bodies are the active implantable devices codes, which are all class III, highest-risk products, according to MDR Annex VIII classification rules (rule 8). The active implantable designation codes are MDA 0101 – MDA 0104 (see table 2, below). Other technologies with very few qualified Notified Bodies include devices manufactured with tissues or cells of human origin (MDS 1002), devices that process and preserve human tissues, cells or organs (MDA 0314), shock-wave lithotripsy devices used to treat stones in the urinary system, pancreas and bile ducts (MDA 0304). Other notable technologies with few designated Notified Bodies include in vitro fertilization and assisted reproductive technologies (active devices: MDA 0314; non-active devices: MDN 1212)), devices for contraception and prevention of sexually transmitted diseases (MDN 1210), devices that use ionizing radiation (MDA 0301), custom-made class III implanted devices (MDS 1013), and devices manufactured using tissues or cells of animal origin (MDS 1003). See Table 3 for a complete list.

Table 3: Designation codes with the fewest (less than 25) Notified Body designations (source: 49 Notified Body certificates in NANDO database):

• But some technologies are covered by all or nearly all 49 designed Notified Bodies. There are two codes that all 49 Notified Bodies received designation to – devices with a measuring function (MDS 1010) and devices that require packaging/labeling (MDT 2011). Forty-eight Notified Bodies received designation for six codes, including software (MDA 0315), systems/procedure packs (MDS 1011), devices manufactured with metal (MDT 2001) or plastic processing (MDT 2002), devices with electronic components (MDT 2010) and devices requiring installation or refurbishing (MDT 2012). See Table 4 for a list of the codes that have the highest Notified Body designations.

Table 4: Designation codes with the most (45 or more) Notified Body designations (source: 49 Notified Body certificates in NANDO database):

• MDR Notified Bodies with the broadest designation: Just two Notified Bodies received designation to all 71 designation codes: BSI Group The Netherlands (NB No 2797) and TÜV SÜD Product Service in Germany (NB No 0123). Fourteen bodies received designation for 60 or more designation codes, including DEKRA in Germany and The Netherlands, TÜV Rheinland LGA Products in Germany and GMED SAS in France. The number rises to 28 Notified Bodies designated for 50 or more designation codes, including NSAI in Ireland, and DQS Medizinprodukte and TÜV Nord Cert in Germany.
• MDR Notified Bodies with the narrowest designation: One Notified Body is a boutique Notified Body, designated for just four codes – Scarlet NB BV in The Netherlands. This Notified focuses solely on medical devices software and software as a medical device (MDA 0315), plus three related codes: devices with a measuring function (MDS 1010), devices with packaging/labeling (MDT 2011) and devices requiring installation or refurbishment (MDT 2012). Eleven more Notified Bodies have designations of 40 or fewer codes out of the 71 total designation codes; a few of these are SLG Prüf und Zertifizierungs (27 codes), AFNOR (31 codes) and SGS Fimko Oy (37 codes).

Analysis:

• Regulators have made significant progress toward designating Notified Bodies to the new regulations, especially the MDR. Of the 62 that applied for MDR designation, 49 have received it. For diagnostics, of the 22 that applied, 12 have received IVDR designation. As compared to the 50 Notified Bodies still designated to MDD, the Commission and designating regulators have achieved parity, though notably this isn’t as high as the 80 Notified Bodies that once had MDD designation. Diagnostic designations aren’t as far along, either compared to applications or the high of 22 designations under the IVDD.
• There are a few concerns in the designation data, though. First, the designation pipeline is empty of designations in the later phases, as shown in Table 2. One of the sticking points in designation is CAPA review, which can take up to two years even in an ideal world, though the Commission and the MDCG have been working to ease the issue with updates to the designation process. It’s clear that some designations have taken even longer, since so many Notified Bodies have received designation in 2022, 2023 and 2024, six or seven years after they could have applied for designation in November 2017. Which leads to the second concern – though MDR is approaching the number of Notified Bodies previously designated under the MDD and AIMDD, about half of them (23 of 49) received designation in 2022, 2023, and 2024. These Notified Bodies haven’t had the time to issue many medical device certificates, which was the concern that led to the last MDR compliance timeline extension in March 2023.
• IVDR designations continues to lag behind MDR designations, as noted above. Part of this is the number of devices vs. the number of diagnostics – medical devices make up about 90% of the total medtech market and diagnostics represent less than 10% of that market. And the designation pace is much slower, generally two a year for IVDR, vs. 8 – 10 for MDR designations – see Figure 1.
• In fact, regulators recently asked for an IVDR compliance deadline extension. The reason for this was a little different than what precipitated the MDR extension discussed briefly above. Rather than a lack of Notified Body capacity, it was more that diagnostic manufacturers weren’t as far along in transitioning to the IVDR. Part of the issue is the more than ten-fold increase in the number of diagnostics that need Notified Body oversight – and those manufacturers aren’t used to Notified Body oversight and may struggle to meet expectations for documentation and clinical evidence, as evidenced by Notified Body measures of the quality of manufacturer submissions.
• Let’s focus on something we just said in the previous paragraph. If 10 times the number of diagnostics need Notified Body oversight under IVDR as did previously under the IVDD, wouldn’t we also need 10 times the number of Notified Bodies to oversee that increase? With the current application numbers, the Commission will have the same number of IVDR-designated Notified Bodies as it did under the IVDD, with just 22 applications for IVDR designation. How will the Commission get more Notified Bodies to apply for designation, and will it be in time for the (soon to be extended) IVDR compliance deadlines? Perhaps some that have withdrawn certification under the IVDD could be enjoined to apply for IVDR designation (see Table 1 above).
• And manufacturers need to find not just any Notified Body, but one designated for their types of technology and devices. Very few Notified Bodies received designation for active implantable devices, for instance. Other technologies with few Notified Bodies to choose from include assisted reproduction, devices manufactured with tissues of human or animal origin and shock-wave lithotripsy devices, to name a few. Manufacturers need to take a close look at each Notified Body’s certificate in order to confirm that their device types are within the Notified Body’s scope of designation, unless they engage the handful of Notified Bodies designated for all or nearly all products.

To contact the author of this item, please email Corey Jaseph ( cjaseph@agencyiq.com).
To contact the editor of this item, please email Kari Oakes ( koakes@agencyiq.com).

Key Documents and Dates

• Single Market Compliance Space (NANDO) database
• Notified Body applications for designation