Medical devices investigations

As a general rule, clinical data are required as evidence to support conformity with the requirements of the Active Implantable Medical Devices (AIMD) and the Medical Device (MD) directives with regards to safety and effectiveness under the normal conditions of use, evaluation of undesirable side effects, and the acceptability of the benefit/risk ratio. Risk analysis should be used to establish key objectives that need to be addressed by clinical data, or alternatively to justify why clinical data are not required (mainly for Class I devices). The risk analysis process should help the manufacturer to identify known (or reasonably foreseeable) hazards associated with the use of the device, and decide how best to investigate and estimate the risks associated with each hazard. The clinical data should then be used to establish the safety and effectiveness of the device under the intended use conditions, and to demonstrate that any of the residual risks are acceptable, when weighed against the benefits derived from use of the device. 

Studies to investigate the safety and effectiveness of In Vitro Diagnostic (IVD) medical devices under intended use conditions are conducted as performance evaluations. They are considered to present less risk than clinical investigations since, by their nature, studies involving IVDs cannot have any direct impact on the health and safety of trial subjects. 

Figure 10.1 Key requirements for the conduct of clinical investigations with medical devices.

The conduct of studies of medical devices in the US that have not been cleared/ approved by the FDA is regulated via Investigational Device Exemption (IDE) regulations set out in 21 CFR Part 812. Considering the type of device and the level of associated risk involved, investigations maybe conducted as IDE-exempted studies. Abbreviated requirement studies, or studies subject to full IDE requirements. 

Investigations of devices that have already received FDA-clearance due to the fact that they were already on the market before medical devices were regulated or were shown to be substantially equivalent to one. 

Figure 10.7 Decision tree for conducting investigations of medical devices in the US.

Clinical trials serve to assess the safety and efficacy of any potential new therapeutic intervention in its intended target species. In our context, an intervention represents the use of a new biopharmaceutical. Examples of other interventions could be, for example, a new surgical procedure or a novel medical device. Veterinary clinical trials are based upon the same principles, but this discussion is restricted to investigations in humans. Clinical trials are also prospective rather than retrospective in nature, i.e. participants receiving the intervention are followed forward with time. 

There are five fundamental elements of FDA regulation of medical devices (1) facility registration and product listing (2) safe use of investigational devices (3) premarket notification (unless exempt) and product labeling ... 

Medical devices are regulated on the basis of a three-level risk classification. The highest risk products are the class 3 products that require premarket applications, almost always with clinical data that demonstrate that the product is safe and effective for the intended use. By default, a novel product is a class 3 product unless there is an approval application for initial approval as a class 2 device (the de novo process). Clinical trials for class 3 products before they are approved usually require an IDE, which is similar to the IND required for investigational drugs. 

E. Medical Device Reporting. The manufacturers, distributors, importers, and users of all devices, including those regulated by CDER, shall report to CDRH under Section 519 of the Act as required. The Center for Devices and Radiological Health will provide monthly reports and special reports as needed to CDER for investigation and follow-up of those medical devices regulated by CDER. 

Thanks are due to the Eederal Institute for Drugs and Medical Devices, Bonn, for financial support and Christine Weber, Yaser Bitar, Daniela Brinz, Susanne Kopec, Frank Wienen, and Nikolai Novatchev, Institute of Pharmacy, University of Wurzburg, for CE investigations and providing the figures to this chapter. 

Compliance with the requirements relating to clinical investigations (AIMDD Annex VII MDD Annex X) is assisted by adoption of standard EN 540 on Clinical Investigation of Medical Devices for Human Subjects, which is very similar to pharmaceutical GCP. 

Guidance Notes for Manufacturers or Clinical Investigations to be carried out in the UK, Medical Devices Agency, September 1996. 

The FDA is responsible for the review and market approval of new drugs, biologies, and medical devices in the United States under the authority of the Federal Food Drug and Cosmetic Act (the Act) and Section 351 of the Public Health Service Act (the PHS Act). The FDA defines premarket review as the examination of data and information in an application as described in Sections 505, 510(k), 513(f), 515, or 520(g) or 520(1) of the Act or Section 351 of the PHS Act. This refers to the premarket review of data and information contained in any Investigational New Drug application (IND), Investigational Device... 

This focus helped field investigators conduct more effective, efficient, and comprehensive inspections of medical device manufacturers by evaluating key elements of a firm s overall quality system and compliance status. This new and improved inspection approach also led to an unprecedented number of administrative, regulator, and judicial actions against the medical device industry. 

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