Medical device regulatory strategy – what you need to know about the US and EU markets (part II)
In the second part of our blog on medical device regulatory strategy, we cover the differences in definitions of medical devices in the United States (US) and the European Union (EU), regulatory pathways, selling medical devices and how to start with your regulatory strategy.
For the introduction to regulatory strategy for medical devices, read the first part: Medical device regulatory strategy – what you need to know about the US and EU markets (part I)
What is a medical device in the US and EU?
Contrary to medicinal products, the rules governing medical device definition, classification, requirements, technical documentation, and product-related processes are not harmonized across jurisdictions, despite the efforts by the International Medical Device Regulators Forum (IMDRF) to align diverging practices. This organization groups medical device regulators from major jurisdictions (including US and EU) “to accelerate international medical device regulatory harmonization and convergence.” Yet, only a few recommendations from the IMDRF have been adopted as they are both in the US and the EU, e.g. adverse event codes and terminology. The definitions of medical device are set forth in the corresponding legislation, and are relatively similar between US and EU, with the EU following IMDRF’s definition more closely.”
Section 201(h) of the US Federal Food, Drug and Cosmetic Act, FD&C Act
“An instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is:
1. recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them,
2. intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
3. intended to affect the structure or any function of the body of man or other animals, and
which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes. The term “device” does not include software functions excluded pursuant to section 520(o).”
Article 2(1) of Regulation (EU) 2017/745 on medical devices (EU MDR)
“any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes:
1.diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease
2.diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,
3.investigation, replacement or modification of the anatomy or of a physiological or pathological process or state,
4.providing information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations,
and which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its function by such means.
The following products shall also be deemed to be medical devices:
- devices for the control or support of conception;
- products specifically intended for the cleaning, disinfection or sterilisation of devices as referred to in Article 1(4) and of those referred to in the first paragraph of this point”
In practice, these definitions are rarely sufficient because the types of products excluded from the scope of the legislation need to be also considered. Moreover, these definitions do not provide details that are needed qualification of new products or ‘borderline’ products, i.e. those without a clear medical intended purpose.
To help manufacturers in determining the regulatory category of a potential medical device, the following regulatory qualification guidelines have been issued:
In the US: How to determine if your product is a medical device. It recommends that, after verifying if the product meets the above definition of a medical device in consideration of its intended use, the manufacturer determines if an appropriate product classification exists for the product. Finding an existing classification that describes the product’s intended use or design is a good indicator that the product might be a medical device. To that end, the fastest approach is to browse the US FDA’s product regulations in Title 21 of the US Code of Federal Regulations (21 CFR) Chapter I, Subchapter H, subparts 862 through 895, where generic types of medical devices are sorted by clinical application.
In the EU: guidance documents (for now only available for the “old” Directive 93/42/EEC on medical devices, MDD) under MEDDEV guidelines to help manufacturers in their qualification of a product as a medical device or an accessory to a medical device that is also subject to the same requirements. Under the new EU MDR, the only guidance document for qualification/classification available at this point is for medical device software, per MDCG 2019-11. All these guidelines are however not legally binding, and in case of disagreement, only the European Court of Justice (ECJ) can issue a binding interpretation of EU law.
After considering definitions, scope exclusions, and qualification guidelines, you might still find that your product is regulated as a medical device in one jurisdiction and not in the other. Typical examples include:
Animal health: medical devices for veterinary use are covered in the definition of medical device in the US but fall outside the scope of the definition in the EU. There used to be a bespoke EU Directive (Dir. 84/539/EEC) that was repealed in 2008 but never replaced, and today medical devices for veterinary use are considered to be consumer products.
Standalone software: web-based tools or mobile apps that either help patients identify potential conditions from common symptoms (i.e. symptom checkers) or provide patient-specific preventive recommendations are medical devices in EU, which are likely to fall under Class IIa or even higher under the EU MDR. In the US, the FDA has taken a pragmatic approach to medical software and, per their Policy for Device Software Functions and Mobile Medical Applications, decided to exercise discretionary enforcement (i.e. they do not enforce medical device requirements) on patient health self-management software.
Drug delivery devices: drug delivery devices that are co-packaged in a kit with the drug but do not form a single integral combination are considered medical devices in the EU and the kit corresponds to a procedure pack, governed by medical device legislation. In the US, drug-device combination products that are co-packaged are governed by specific legislation and overseen by a bespoke department within the US FDA, the Office of Combination Products (OCP).
What determines the regulatory pathway in the US and EU?
The type of regulatory scrutiny and market clearance needed depends on the medical device classification, which follows similar principles in the US and EU: devices are classified based on their inherent risk. The classification similarities have increased with the enhanced classification rules in the new EU MDR, e.g. on invasive devices for transient use, for which continuous use now needs to be considered. In the EU, the manufacturer is responsible for determining the appropriate classification for its device, following the classification rules in Annex VIII of the EU MDR, and for choosing the corresponding regulatory pathway.
|EU medical device classes||EU regulatory pathway (for CE marking)|
|Class I (low risk)||They can be CE-marked by self-declaration of the manufacturer, without the involvement of a Notified Body, once the manufacturer has compiled evidence of conformity with the relevant General Safety & Performance Requirements (GSPR) in EU MDR Annex I.|
|Class I and either:
– sterile (Class Is)
– with measuring function (Class Im), or
-reusable surgical instruments (Class Ir)
|Their conformity assessment process for CE-marking requires the involvement of a Notified Body only for the specific aspects: sterilization, measuring function, or reprocessing. To that end, the manufacturer must lodge an application with the Notified Body of its choice, and submit the appropriate evidence of Quality Management System and device Technical Documentation.|
|Class IIa (medium risk)||Their conformity assessment process for CE-marking requires full involvement of a Notified Body. To that end, the manufacturer must lodge an application with the Notified Body of its choice, and submit the appropriate evidence of Quality Management System and device Technical Documentation.|
|Class IIb (medium/high risk)||Their conformity assessment process for CE-marking requires full involvement of a Notified Body, with higher level of scrutiny than for Class IIa devices, particularly in terms of safety.
To that end, the manufacturer must lodge an application with the Notified Body of its choice, and submit the appropriate evidence of Quality Management System and device Technical Documentation.
|Class III (high risk)||Their conformity assessment process for CE-marking requires full involvement of a Notified Body. To that end, the manufacturer must lodge an application with the Notified Body of its choice, and submit the appropriate evidence of Quality Management System and device Technical Documentation.|
In the US, the FDA establishes the classification for generic types of medical devices, per classification panels corresponding to clinical applications. The classification for a given type of device is added to its Product Regulation in the corresponding section of Title 21 of the US Code of Federal Regulations (CFR) according to their medical specialty and are assigned a 3-letter Product Code. The manufacturer merely takes the classification and regulatory pathway established in the applicable Product Regulation and, in case of uncertainty or disagreement with a given classification, an official request to US FDA for opinion can be filed through the 513(g) process.
|US medical device classes||US regulatory pathway|
|Class I (low risk)||The devices in this class are mostly exempted from premarket notification to the US FDA and from Good Manufacturing Practice (GMP) per the Quality System Regulations (QSR). A list of exemptions is available from the US FDA website.
For exempt devices, the only requirements that apply are:
– establishment registration,
– device listing,
– complaint handling & medical device reporting, and
– device labeling.
|Class II (medium risk)||The devices in this class are mostly subject to a premarket notification to US FDA is required, i.e. via 510(k) submission in case an equivalent (‘predicate’) device has been previously approved or via De Novo submission in case there is no predicate.
Some Class II devices in the lowest risk range are exempt of premarket notification but not of GMP compliance.
|Class III (high risk)||The devices in this class are subject to the strictest regulatory process, i.e. premarket approval (PMA) by the US FDA.|
Despite classification similarities, your medical device might still fall under different risk classes in the US and in the EU. It is therefore important to ensure clarity on the classification and regulatory pathway in both jurisdictions.
In some cases, a classification difference might not result in a more cumbersome path to market in one jurisdiction than in the other. For example, a surgical lamp intended to illuminate the patient’s body as a surgical field would be a Class II device in the US, per product regulation 21CFR878.4580. In the EU, it would be a Class I active device, per EU MDR classification rule 13, thus subject only to self-declaration of conformity for CE marking. In practice, by virtue of US FDA’s exemptions, the Class II surgical lamp in the US would not require a premarket submission and could be placed on the US market without regulatory oversight by the US FDA.
Who can sell a medical device in the US and EU?
In both the US and EU, foreign manufacturers (i.e. entities not located in the territory) can hold regulatory approvals for medical devices but they need a local representative within the territory, and they can sell medical devices though an official local importer. However, the roles and duties of those entities significantly differ in the US and EU. So does the role of “manufacturer”. Specifically:
A foreign manufacturer needs a US Agent.
The US Agent has limited responsibilities, mainly as liaison agent between the FDA and the foreign establishment, and no responsibility related to reporting of adverse events under the Medical Device Reporting regulation (21 CFR Part 803), or submitting 510(k) Premarket Notifications (21 CFR Part 807, Subpart E).
A medical device that enters the US from a foreign country needs an Initial Importer located in the US.
The Initial Importer must be staffed by individuals responsible for ensuring the compliance of imported devices with all applicable US FDA laws and regulations, and is subject to establishment registration.
In the US, the role of manufacturer is basically associated with the producer, regardless of whether some activities are subcontracted. The role is not linked to the holder of regulatory approvals/clearance.
Per US FDA’s 21 CFR 820.3 (o), Manufacturer means “any person who designs, manufactures, fabricates, assembles, or processes a finished device.
Manufacturer includes but is not limited to those who perform the functions of contract sterilization, installation, relabeling, remanufacturing, repacking, or specification development, and initial distributors of foreign entities performing these functions.”
Repackagers and relabelers who place a device on the market under their own name are not considered manufacturers and can rely on regulatory approval/clearance obtained by another company.
A foreign manufacturer can be the CE-mark owner (i.e. “legal manufacturer”) but it needs an EU Authorized Representative (EAR).
The EAR bears significant regulatory responsibilities, per EU MDR/IVDR Art. 11, as it is actually liable for defective medical devices together with the foreign manufacturer, in case of non-compliance. Therefore, the EAR must therefore verify and keep copies of conformity assessment documents.
A medical device that enters the EU from a third-country needs an EU Importer located in any country of the EU single market.
The EU Importer is subject to substantial regulatory responsibilities, per EU MDR/IVDR Art. 13. These include compliance verification, post-market surveillance, and registration duties in the EU-wide database EUDAMED.
In the EU, the role of manufacturer corresponds to the entity that owns CE-marking and, thus, endorses the ultimate regulatory responsibility for compliance. The role is frequently referred to as “legal manufacturer” to differentiate it from a mere producer.
Per EU MDR Art. 2(30) or IVDR Art. 2(23), Manufacturer means “a natural or legal person who manufactures or fully refurbishes a device or has a device designed, manufactured or fully refurbished, and markets that device under its name or trade mark.”
Moreover, per EU MDR/IVDR Article 16, distributors and importers (or other persons) might assume the responsibility of the “legal manufacturer” if they sell the device under their name, modify the device’s intended purpose or its characteristics in a manner that affects the applicable requirements.
Given the above differences, your company might find itself in conflicting roles between the US and EU. For example:
- If you are a US manufacturer wanting to sell in the EU a device you produce but for which you are not the holder of a 510(k) clearance by the US FDA, you would be seen as the “legal manufacturer” in the EU and would need to generate your own proof of safety and performance for the device and adapt your quality management system to obtain CE marking. And you would need an EU Authorized Representative.
- If you are a US private labeler or distributor who has re-packaged/re-labelled someone else’s medical device, you would be seen as the “legal manufacturer” in the EU. And you would need an EU Authorized Representative.
- If you are an EU private labeler wanting to sell a device from the original manufacturer in the US, you could rely on the US FDA’s clearance/approval obtained by the original manufacturer and would be considered a foreign relabeler/repackager.
Because medical device distribution chains can become very complex when several entities are involved, it is strongly recommended to verify your set-up with particular focus on whether you would be endorsing the regulatory responsibilities for compliance. To simplify the burden of becoming a “legal manufacturer” for CE-marking, Decomplix offers third-party CE marking services. For more information, see our services.
Where do you start with the regulatory strategy?
The development of an efficient regulatory strategy is a challenging task that requires in-depth knowledge and experience with the regulatory requirements of the target markets. In addition, sufficient professional and personnel resources, a sensible sequence of market entries, and detailed knowledge of the target markets are also required. Proper and complete technical documentation is indispensable for mastering regulatory requirements worldwide, regardless of their differences. The basis for the approval/certification of your product is, therefore, already laid during the development phase by defining and documenting all relevant processes with an effective quality management system (contact us if you have questions about an effective QMS).
Despite all the differences, there are some common regulatory requirements in the EU and the USA. In certain cases, details are crucial as they can significantly impact the responsibilities of different economic actors. Our team of experts will be happy to support you in the development of the regulatory strategy as well as in specific questions regarding the regulatory requirements for your medical device in the EU and the USA.