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Launch Medical Device to Market in US & EU
Build the optimal regulatory strategy for smooth, successful medical device launches in multiple markets
Introduction
Taken together, the value of the medical device markets in the United States (U.S.) and European Union (EU) totals more than US$288 billion. For medical device manufacturers, launching in both markets represents a major opportunity to build share and drive business growth.
Although there are many shared regulatory requirements in both regions, there are also important differences. Failing to prepare for the specific demands of U.S. and EU approval pathways can result in significant go-to-market costs and delays.
In this eBook, we explore the challenges of bringing medical devices to market in the EU and in the U.S., explain how to design an effective regulatory strategy, and describe best practices to help accelerate the regulatory journey.
Identifying the opportunity
The U.S. and EU medical device markets have a combined value of over US$ 288 billion, growing at more than 4.25% a year. In the past, there was a perception among some manufacturers in Europe that the barriers to entry were higher in the U.S., as the U.S. Food and Drug Administration (FDA) set more stringent requirements than regulatory authorities in Europe. As a result, some businesses pursued approval in the EU first, before attempting the apparently higher hurdle set by the FDA.
The introduction of the EU Medical Device Regulation (MDR) in 2017 reversed this trend. Following the introduction of the MDR, a substantial number of manufacturers decided to focus on FDA approval, deferring the perceived complexity of getting to grips with the new requirements in Europe.
Wherever manufacturers choose to begin their regulatory approval journey, it is important to understand the regulatory pathways available in each market and to develop an efficient strategy that takes all the appropriate requirements into account.
Most importantly, the U.S. regulations share a single legislative framework, language, and a single set of requirements for medical devices; by contrast, the 27 EU member states are free to implement their own specific requirements on top of the EU legislation. In addition, countries such as the UK and Switzerland have introduced their own national regulations for medical devices.
Assessing the differences
When we look a little deeper, some more differences begin to emerge between the U.S. and EU regulatory regimes.
In most instances, what counts as a medical device in one jurisdiction will also count as a medical device in another—but this is not always the case. For example, in the U.S., veterinary products fall within the same legislative framework as medical devices intended exclusively for human use. In Europe, the definition of a medical device encompasses only products designed for humans; under current EU legislation, medical devices for veterinary use are classed as consumer goods. Similarly, in the U.S., a single piece of legislation governs medical device development, while in the EU there are two: the MDR and the In Vitro Diagnostic Regulation (IVDR).
Because of the many differences between the regulatory regimes, medical device manufacturers that aim to bring their products to market in the U.S. and the EU should carefully consider the intended use of their device, any claims related to their device, and which legislation may apply in each jurisdiction.
Definition of a medical device: U.S.
Source: FD&C Act, 21 USC § 321(h)(1)
(1) The term “device” (except when used in paragraph (n) of this section and in sections 331(i), 343(f), 352(c), and 362(c) of this title) means an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is—
(A) recognized in the official National Formulary, or the United States Pharmacopeia, or any supplement to them,
(B) 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
(C) 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 360j(o) of this title.
Definition of a medical device: EU
Source: Regulation (EU) 2017/745
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:
diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease
diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,
investigation, replacement or modification of the anatomy or of a physiological or pathological process or state,
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.
Common regulatory pathways in the U.S.
U.S. and EU authorities have adopted regulatory pathways based on risk. In the simplest terms, a device which has the potential to cause serious harm attracts more-stringent requirements than a device where the risk of serious harm is negligible.
In both markets, the regulatory process begins by classifying devices into risk-based categories. In the U.S., medical devices are assigned to one of three regulatory classes, in which Class I represents the lowest level of risk and Class III the highest. The FDA oversees the regulatory process through pathways such as 510(k), Premarket Approval (PMA), and De Novo. Generally, Class I devices need only be FDA registered; Class II devices must be FDA-cleared; Class III devices must go through PMA, which is the most-extensive regulatory approval pathway.
In the U.S., device manufacturers may be able to streamline their regulatory pathway by making use of FDA exemptions. For example, the FDA 510(k) clearance may allow manufacturers to avoid the need to provide clinical data if they can show their device is sufficiently similar to another device that is already on the market. In general terms, the lower the risk classification of the device, the more potential exemptions that are available to manufacturers.
Regulatory pathways in the U.S.
Class I devices:
Exemption
510(k) clearance
De Novo Classification Request
Class II devices:
510(k) clearance
De Novo Classification Request
Class III devices:
Premarket Approval (PMA)
Common regulatory pathways in the EU
The EU MDR, like the U.S. FDA, adopts risk-based classification for medical devices. The process in Europe, based on CE marking, places responsibility on the device manufacturer for ensuring that their device is compliant with the applicable EU regulation. The CE mark denotes that a product has been assessed—either by the manufacturer through a self-declaration, or by a competent authority—to meet all applicable safety, health, and environmental protection requirements.
There are a number of ways for medical device manufacturers to gain a CE mark for their devices, and the process becomes increasingly stringent based on the level of risk. The MDR categorizes devices from Class I (the lowest level of risk) to Class III (the highest level of risk), with intermediate categories such as Class Im (for low-risk measuring devices) and Class IIa (for low- to medium-risk devices), among others. For devices that fall under the IVDR, the categories range from Class A (the lowest risk level) to Class D (the highest risk level).
For both the MDR and IVDR process, it is possible for manufacturers of low-risk devices to make a self-declaration that their products meet the requirements of the applicable legislation. In these situations, products can be brought to market in Europe without going through an initial external approval process. However, higher-risk devices must be externally reviewed and approved by a Notified Body.
In the EU, notified bodies are independent organizations that have been accredited to review and grant CE markings for medical devices in their specific field(s) of expertise. Unlike the U.S. where the FDA is the sole competent authority for medical devices, in the EU, there are multiple notified bodies.
For European countries that are not EU members, the regulatory landscape looks slightly different. Before it was superseded by the MDR and IVDR, the Medical Devices Directive (MDD) was the key piece of EU legislation. During the period in which the MDD was in force, Switzerland had a mutual recognition agreement with the EU that would allow non-Swiss companies to market their CE-marked devices in Switzerland. However, this agreement was not extended with the introduction of the MDR and IVDR, and Switzerland has since introduced its own requirements. However, FDA-approved devices may be sold in Switzerland without further approval—which means that manufacturers that wish only to target Switzerland and the U.S. have a relatively streamlined path to market.
The UK, a market of around US$18 billion, has its own legislation governing the sale of medical devices. However, there is currently a grace period during which EU CE markings are being accepted by the UK’s competent authority, the Medicines and Healthcare products Regulatory Agency (MHRA). At some future date, medical device manufacturers will need to pass the MHRA certification process to bring devices to market in the UK.
Regulatory pathways in the EU
CE Marking
MDR:
Class I:
Self-declaration
Class Is, Im, Ir:
Limited notified body involvement
Class IIa, IIb, III:
Approval by a notified body
IVDR:
Class A:
Self-declaration
Class B, C, D:
Approval by a notified body
Building the optimal regulatory strategy
Understanding the differences between the regulatory pathways in the EU and the U.S. gives medical device manufacturers the potential to unlock valuable efficiencies when bringing their products to market in both regions.
When building a regulatory strategy, manufacturers should consider the following best practices:
Start early: Regulatory requirements will inevitably influence your design and development processes, which means it is crucial to analyze and consider which requirements from each market—EU and U.S.—will apply as early in the project as possible.
Take a comprehensive approach: Determine the similarities and differences between EU and U.S. regulation, including the specific documentation necessary to obtain initial market access and ongoing compliance with reporting and post-market surveillance requirements.
Think bigger: Don’t restrict regulatory planning to medical device regulations alone. Instead, consider which other standards, guidelines or requirements may apply—for example, the EU General Data Protection Regulation (GDPR) or the U.S. Health Insurance Portability and Accountability Act (HIPAA).
Assess the risks: Risk management must be a key focus area for any medical device manufacturer, and risk analysis should encompass the entire lifecycle of the device. More broadly, manufacturers should consider the business risks associated with their regulatory strategy; for example, that a delay entering one market may prevent entry into another.
Engage with regulators: In the U.S., manufacturers have one port of call for advice on the regulatory approval process, but in the EU it may be less obvious where to turn. Manufacturers should identify and connect with the appropriate notified body early on in the process to understand their expectations and the likely timelines.
Stay informed: In both the EU and the U.S., the regulatory landscape and medical device market are constantly evolving. By monitoring these changes, manufacturers will be well placed to adapt to keep their journey to market moving forward smoothly.
When it comes to building a regulatory strategy, it is important to bear in mind that there is no one-size-fits-all approach that will deliver the same benefits for every company. To create the optimal strategy, manufacturers must take account of a large number of variables, including the type of medical device and its risk classification(s), the testing and/or clinical evaluation requirements for each market, the possibility for regulatory exemptions and self-declarations, and mutual recognition agreements that may exist between the U.S. and Europe.
As an example, consider a medical device manufacturer that wants to bring a new surgical lamp to market in the U.S. and EU. Under the MDR, the lamp would be defined as a low-risk Class I device, meaning the manufacturer could use a self-declaration to market the device in the EU. The same device would be considered Class II in the U.S., which would generally imply that an FDA clearance process is required. However, the manufacturer could use an FDA exemption to bring the device to the U.S. market without direct regulatory oversight.
Avoiding duplication of effort
A simple, powerful strategy for multi-region approval is to determine the shared standards that apply to each device, and explore the synergies between regulatory processes in the EU and U.S.
Taking risk management as an example, regulators in both markets recognize ISO 14971:2019 as a reference standard, which means that following the standard will go a long way towards satisfying competent authorities in both the U.S. and EU. By following harmonized standards such as ISO 14971 for risk management, IEC 62366-1:2015 for usability engineering, and IEC 60601-1 for electrical equipment, manufacturers can ensure that their design and development work addresses requirements in both target markets.
Another effective approach is to invest time early in the project to define a single set of documentation templates that will be suitable for regulators in the U.S. and the EU. By capturing documentation requirements around procedures, specifications, and risk management plans, manufacturers can build templates that satisfy the requirements of the FDA as well as the MDR and/or IVDR. In addition to saving a significant amount of time, producing only one set of documentation significantly reduces the risk of human error.
Naturally, there will be market-specific requirements that require their own individual documentation templates—for example, incident-reporting processes differ in the U.S. and the EU. However, standardized templates can still be useful; manufacturers can describe the timelines for reporting in a central procedure, and then link to market-specific templates or work instructions. By creating procedures that cover the requirements of both the EU and U.S. with specific work instructions and templates to handle regional differences, manufacturers can reduce duplication of effort, make updates to their procedures more quickly, and improve overall visibility for regulatory processes.
To help ensure a smooth and ultimately successful regulatory journey, it is vital for manufacturers to maintain tight control over their documentation at every stage of the lifecycle. For this reason, leveraging digital solutions is an extremely effective way to minimize duplication of effort. Solutions such as MatrixALM and MatrixQMS are purpose-built by medical device experts to help manufacturers control quality-related processes, streamline requirements management, and compile documentation for regulatory submissions automatically.
Conclusion
This eBook outlines the differences and similarities between regulatory pathways in the U.S. and the EU, and highlights the importance of understanding the nuances of both regions to create an efficient regulatory strategy.
Naturally, the product itself, its intended use, and the associated medical claims will determine the applicable legislation, risk classification, and regulatory requirements. By identifying the regulatory requirements in each market, manufacturers can create a strategy that engages with the FDA and EU processes with minimal duplication of effort. Keeping a watchful eye on changes to the regulatory landscape in both regions throughout this process will empower manufacturers to quickly adapt their approach if required.
Ultimately, all stakeholders—including the FDA, notified bodies in Europe, and medical device manufacturers themselves—share the overarching goal of ensuring the safety and efficacy of medical devices. By considering the commonalities and differences of the U.S. and EU markets, manufacturers can avoid the cost and delay of independent regulatory frameworks, and greatly accelerate their journey to market.
Key takeaways
Understand the applicable regulatory requirements in all your target markets
Set aside time to plan out your regulatory pathway for the U.S. and EU
Leverage similarities between regulations in both markets to reduce duplication and drive efficiency
Stay alert to regulatory and market changes and be ready to adapt