Medical device regulation: an overview

Amit Salvi, ELC Group, provides a regulatory overview of medical devices

The medical device industry is a crucial part of the healthcare sector. The global medical device market is expected to reach $440 billion by 2018, growing at about 4.4% per year. Contrast that with the prescription drug market, predicted to grow at an annual rate of 2.5%. Established players in this industry include the United States and Western Europe. But industry trends show that Asia and importantly, China are about to play a prominent role in the next few years.

The Global Harmonization Task Force classifies medical devices into class A, B, C and D, with class D representing the highest risk.

U.S. Regulation: Medical devices are regulated under the Federal Food Drug & Cosmetic Act (FD&C Act) Part 800-1299. Manufacturers importing medical devices into the USA must designate a United States agent, register the establishment, list the device, manufacture according to the quality system requirements and file a Premarket Notification 510 (k) or a Premarket Approval. A post-marketing surveillance system is required (21 CFR Part 803). Medical devices are divided into Class I, Class II and Class III, where class I devices represent the lowest risk and class III devices represent the highest risk. Most Class I devices and some Class II devices are exempt from a Premarket Notification 510 (k). Class II devices generally require a 510 (k) while Class III devices require a Premarket Approval.

EU regulation: Regulation in the EU differs from the U.S., in that medical devices bearing a CE mark can be freely marketed across Europe. Overall, the requirements for obtaining an EU CE mark are more straightforward and less time-consuming than those for a U.S. FDA approval. The Medical Devices Directives (MDDs) form the foundation of Europe’s regulatory framework for medical devices. A manufacturer that does not have a registered place of business in the EU can designate a single authorized representative in the European Union. Medical devices are divided into class I, class IIa, class IIb and class III, where class I also has the subclasses Sterile and Measuring. All medical devices except class I devices require the involvement of a Notified Body

EU Clinical Trial Requirements:

Regulatory requirements for clinical investigations of medical devices are different to those for pharmaceuticals, as there is no legal requirement to demonstrate the efficacy of the device in order to obtain CE marking. The objective of the device clinical trials is to demonstrate the safety and performance (conformity with claims) of a medical device. The stage of a clinical investigation which needs to be satisfactorily completed for CE marking is most likely Phase II, where evidence of clinical activity of a drug is sought, rather than Phase III.

The relevant EU legislation addressing the clinical evaluation of medical devices is the Medical Device Directive 93/42/EEC, as amended (March 2010) and the Active Implantable Medical Device Directive 90/385/EEC, as amended (March 2010). This legislation was transposed into national law in all concerned countries. 

The type and amount of clinical data needed primarily depends on the specifics of the clinical claims with regard to clinical performance, considerations of clinical safety – including determination of undesirable side-effects – and on risk management output, namely determination of residual risks and favorable benefit/risk ratio.

The Conformity Assessment process for active implantable medical devices as well as for class III and implantable medical devices requires that a clinical investigation is undertaken, unless it is duly justified to rely on existing data. Any such justification will have to be based on a proper clinical evaluation. Depending on clinical claims, risk management outcome, and on the results of the clinical evaluation, clinical investigations may also have to be performed for non-implantable medical devices of classes I, IIa and IIb. Additional clinical investigations may be feasible to corroborate the existing clinical evidence with regard to aspects of clinical performance, safety, benefit /risk-ratio, or to determine relative effectiveness and safety with suitable comparators. Manufacturers have to submit the results from any clinical trial, but there is no obligation to discuss the design of the study with the Notified Body or a regulatory agency prior to the trial.