So far we have indicated that it is easier for medical device manufacturers to obtain approval to sell their products in Europe first, then, apply to the US Food and Drug Administration (FDA) for clearance or approval in the United States.  This blog addresses why that is so. Although none of the approval processes are inexpensive, at least if the product has been awarded the CE Marking, it can be sold in Europe to offset approval expenses and fund the company while working toward FDA approval.  Since the FDA process is notoriously slow and very expensive, it is often necessary to have good cash flow during the approval process.

According to their web site, the FDA has established classifications for approximately 1,700 different generic types of devices and grouped them into 16 medical specialties referred to as panels. Each of these generic types of devices is assigned to one of three regulatory classes based on the level of control necessary to assure the safety and effectiveness of the device. These classes are Class I, Class II, and Class III, which depend upon both the device’s intended use as well as the indications for use. Each of the classifications has their own set of guidelines and rules for approval.

FDA has exempted almost all Class I devices from the premarket notification [510 (k)] requirement, which includes such devices as hearing aids and otoscopes.  The FDA has also exempted a variety of Class II devices, for example, audiometers, because they believe that these exemptions will relieve manufacturers and enable FDA to redirect their resources that would be spent on reviewing such submissions to more significant public health issues.

Although exempt from requiring a submission to market these devices, they are not exempt from other general controls. All medical devices must be manufactured under a quality assurance program, be suitable for the intended use, be adequately packaged and properly labeled, and have establishment registration and device listing forms on file with the FDA.  At the other end of the scale are Class III devices, where the road to approval becomes extremely costly, lengthy, and involving detailed scientific research.

510 (k) and General Controls

This application requires demonstration of substantial equivalence to another legally U.S. marketed device.  Substantial equivalence means that the new device is at least as safe and effective as the device currently on the market, has the same intended use, the same technological characteristics, and if the characteristics are different, that it does not raise new questions of safety and effectiveness. These Class II devices requiring submission of a premarket notification include tinnitus maskers and bone-conduction hearing aids.

Sophisticated Implantable Devices

Class III devices are those that are the most sophisticated and often involve life support and often implantation. Therefore, they require  the greatest scrutiny. In Audiology, cochlear and middle ear implantable products fall into the Class III category. For these complex medical devices, a pre-market approval process is generally required. The FDA (2011) defines this premarket approval process (PMA) as the most stringent type of device marketing application. They further indicate that the PMA process of scientific and regulatory review is to evaluate the safety and effectiveness of devices  that are  implanted

Esteem, Envoy Medical, FDA Approved March 2010

or support or sustain human life. These devices could be of substantial importance in preventing impairment of human health and/or present a potentially, unreasonable risk of illness or injury. Approval of the PMA is based upon an FDA determination that sufficient, valid scientific evidence has been obtained to assure that the device is safe and effective for its intended users.

One of the most important sections of the PMA is the Clinical Investigations’ Section.  This section includes the study protocols, safety and effectiveness data, adverse reactions and complications, device failures and replacements, patient information, patient complaints, tabulations of data from all individual subjects, results of statistical analyses, and any other information from the investigation.

FDA states on their website that if the application lacks any of their required elements or valid clinical information and scientific analyses, they will delay their review and approval until the submission meets their requirements, or they will completely deny the PMA application. They caution that manufacturers should perform a quality control audit of the application before sending it to FDA to assure that it is scientifically sound and presented in a well organized format.  It is obvious that these requirements may extend the approval process out months or even years before marketing of the device may be granted.

To put this issue in perspective, the table below is a synopsis of some middle ear implants that have gone through the regulatory process in both the EU and US.  As is evident in following table, all companies