Medical Device and Diagnostics Clinical Investigations—A Sea-Change in Route to Market

Adam Steadman, Syneos Health

Clinical Researcher—May 2018 (Volume 32, Issue 5)

DEVICES TODAY

Adam Steadman

[DOI: 10.14524/CR-18-4028]

 

The approach to the global development of medical devices is going through a sea-change. The global market for medical devices is growing at tremendous rates, particularly in the Asia-Pacific region, and not only in historic sectors such as cardiovascular and orthopedics, but in other sectors too, including non-reimbursed medical aesthetics.

The traditional approach to device development, which involved obtaining CE Marking first, followed by European commercialization and then U.S. and other global approvals, is being challenged. This challenge is driven by the economics of more stringent regulations in Europe, a softening of the requirements in the U.S., and changes by the regulators in countries like China that are allowing for better, faster, and higher standards of product approvals.

Taking a commercial view, manufacturers can redesign their clinical development programs to get their products to the market faster and more efficiently, save money, and realize a faster return on investment.

Around the World in Device Development…

Let’s take a look at this more closely. The traditional approach has very often been to seek CE Marking first, as this required limited or no clinical studies for most devices prior to 2011. This provided the manufacturer with the opportunity to market the product and generate income while going through more rigorous or time-consuming approval processes elsewhere.

With the changes in the European MedDev regulations in recent years, and a complete overhaul of these regulations with the replacement MDR and IVDR regulations coming into effect in May 2020 and May 2022, respectively, this approach may no longer be optimal for all devices and therapies.

The European Union (EU): Greater Evidence Requirements

There is a significantly greater requirement for clinical data in the new EU regulations—consequently, substantial pressure has been put on the entire European regulatory ecosphere. This pressure will, on its own, create substantial change in the European markets.

Notified Bodies (to whom the responsibility for CE Marking approvals is delegated by the Designating Authority) are under siege. Every Notified Body has to apply for re-designation—meaning they have to show the Designating Authority that they themselves are capable of making all the necessary evaluations to certify a product as being worthy of the CE Marking.

This re-designation process works by having categories split into MDA codes for active devices and MDN codes for non-active devices, though not all Notified Bodies will choose to re-designate under each code, or part of a code. Some Notified Bodies may even fall short of the expectations of the Designating Authority and fail in their applications.

The natural consequence of this re-designation process is that there will be fewer Notified Body resources available to manufacturers worldwide. This has already begun to force the Notified Bodies to reconsider how they do business.

Initially and progressively, there will be a need to hire more experienced experts in the clinical development arena, who will be drawn from the manufacturer/contract research organization/consultant market. Some Designating Authorities are making clear to the Notified Bodies an expectation that they cannot offer to provide services for customers unless they can demonstrate the ability to perform the work.

The need to generate clinical evidence will also result in a process of product rationalization. Manufacturers will have to weigh the future returns on products that will need costly clinical trials, which could have serious effects for products treating rare diseases and injuries.

With this pressure on the existing market place, there will likely be a significant resultant barrier to entry to business start-ups. If Notified Bodies are unable to accept new business, these new entities will struggle and likely be delayed in their attempts to access the European market, but also other markets such as in Australia and Canada, where the CE Marking is an important stepping stone to approval.

The United States: A Welcoming Alternative

It is clear that the European regulatory environment will be a lot tougher than it has ever been in the past, which then begs the question: What are the alternatives? Most manufacturers will turn to the United States as the biggest market in the world for medical devices.

Over recent years, we have seen changes at the U.S. Food and Drug Administration (FDA) that have shown a definite desire to become more user-friendly, customer-driven, and sensitive to the needs of the medical device industry. This includes changes that have been made based on the 21st Century Cures Act (Cures Act), which requires the FDA to consider the “least burdensome approach” to product approval.

Many of us in the clinical research arena will initially blanch at the prospect of waiving the requirement for informed consent, but this is a positive development that has now been facilitated through the Cures Act. This applies in cases when the device poses no health risks beyond those of normal everyday life, yet the studies still require institutional review board/ethics committee approval.

The Cures Act also paved the way for the Breakthrough Devices program, “intended to help patients have more timely access to these medical devices by expediting their development, assessment, and review, while preserving the statutory standards for premarket approval, clearance of a premarket notification (510(k)), and marketing authorization via the De Novo classification process.”{1}

China: Active Reforms

In China, the Central Committee of the Chinese Communist Party together with the State Council have been making changes with a view to improving innovation in healthcare and, by default, China’s desirability as a venue for clinical trials. The China Food and Drug Administration (CFDA) has been through major overhauls of its processes over the last two or three years, which has initially slowed down the process of getting study approval, but this has largely been done to protect the health and safety of China’s citizens.

In October 2017, the Chinese authorities introduced what is known as the “Innovation Opinion,” which sets out 36 provisions aimed at reforming the regulatory process for drugs, devices, and diagnostics. While some of these provisions are directed at drugs, there are some significant provisions that impact the medical device and diagnostics landscape. At the same time, Beijing also voiced its commitment to protection of patents and other intellectual property.

Not only does the Innovation Opinion look at facilitating domestic innovation, it considers the reform of the marketing authorization process, clinical trial management, and enforcement. Furthermore, the Innovation Opinion was not just conjecture; many draft regulations have since been issued, with new additions almost every month.

Within the first month, the CFDA published draft amendments to the medical device regulations, along with several proposed changes to the drug rules. Early in 2018, draft rules for Marketing Authorization Holders were published, effectively removing the requirement for local innovators to also be manufacturers.

Also in January 2018, technical guidelines were issued for the acceptance of foreign clinical trial data for medical device and diagnostics applications. These are similar to the FDA rules that allow for data from foreign studies that can be demonstrated to have been conducted to the same standards, ethics, and on comparable populations as they would be if conducted under U.S. regulations.

In March 2018, Beijing announced sweeping reforms to the structure of China’s regulatory agencies (not just for drugs and devices, but also for food, cosmetics, consumer protection, advertisements, and more) in the form of a proposed new State Market Regulatory Administration—making it very clear that China is committed to the 36 provisions of the Innovation Opinion.

Final Thoughts

In conclusion, the major global markets for medical devices and in-vitro diagnostics are getting closer to regulatory equilibrium with respect to market authorization. This presents sizeable opportunities for efficiencies in clinical trial designs through shared use of data across multiple geographies with significant cost benefits and, most importantly, earlier access for patients to new technologies.

Reference

  1. U.S. Food and Drug Administration. 2017. Breakthrough Devices Program: Draft Guidance for Industry and Food and Drug Administration Staff. https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM581664.pdf

Adam Steadman is Vice President—Clinical Development; Business Unit Head, Medical Device & Diagnostics at Syneos Health.