Thursday, April 22, 2010
Featured Article
Check out our Medical Device CRO section for more information or to find companies that provide these services.
Medical devices include everything from a simple Band-Aid to a sophisticated CAT scan. Like many industries, medical devices are highly regulated by the US Food and Drug Administration (FDA). As a result, medical device companies must invest significant time, money, and manpower to bring a device from the development stage to market. Diagnostics, such as assays, instruments, and reagents used in the diagnosis and screening of diseases, are also regulated as medical devices; an example of a diagnostic is the glucose meter used by diabetics.
A medical device company can choose to either perform all of the steps necessary to develop and market a device, or they can hire a medical device contract research organization (CRO) to perform several or all of those steps. Some medical device CROs provide consulting services only. Medical Device Consultants, Inc. (MDCI) (North Attleboro, Mass.) is one such company; they cover the gamut of medical devices and diagnostics. MDCI provides “regulatory and quality/compliance consulting services, as well as the supporting the usual clinical trial activities associated with these regulated products,” says Vicki Anastasi, vice president of regulatory services and business development for the company.
Some of the therapeutic areas commonly worked on by a medical device CRO include cardiovascular, orthopedic, diabetes care, wound care, radiology, neurology, and general hospital/general surgical equipment. A typical scenario for a regulatory consulting project includes the development of an appropriate regulatory strategy and design of clinical study to meet specific FDA requirements. These strategic planning projects frequently involve early meetings or conversations with the FDA. A medical device CRO will often assist their clients with these conversations with the goal of developing a structure for necessary clinical trial work required by the FDA. “After assisting with the design of a clinical trial, a CRO will manage study activities, monitor the study, ensure that it is being conducted in accordance with the approved study protocol, collect and manage the study data, and work with the client or sponsor to create the final data package and study report that is required for the required 510(k) or premarket approval (PMA) application submission that is sent to FDA to gain marketing authorization,” says Anastasi.
Regulation
The FDA categorizes medical devices and diagnostics into three regulatory classes: Class I, Class II, and Class III. This classification is based on a number of factors, including: level of control necessary to assure safety and effectiveness, the device’s intended use and indications for use, and, finally, the risk that a product poses to the patient and/or the user. Class I includes devices with the lowest risk and Class III includes those with the greatest risk. The majority of medical devices commercialized in the United States fall into Class II, and require a 510(k) submission to the FDA. The 510(k) is used to demonstrate that the medical device is at least as safe and effective as, or substantially equivalent to, a predicate device already cleared for marketing by the FDA. According to Anastasi, the Center for Devices and Radiological Health (CDRH) within the FDA receives nearly 4,000 510(k) submissions annually. While not all 510(k) submissions require human clinical data, the FDA has recently become more stringent and is asking for more clinical studies to support 510(k) submissions, especially in the case of more complex technologies.
A PMA is generally required for a Class III device. This is the most stringent type of device marketing application required by the FDA, and must provide sufficient valid scientific evidence to assure that the device is safe and effective for its intended use(s). When there is a question about the amount or type of clinical data required to support either a 510(k) or PMA submission, a medical device CRO will recommend that their client participate in an early meeting with the FDA, called a pre-IDE meeting, to clarify the agency’s requirements and the expected regulatory pathway. “A pre-IDE meeting is a nonbinding discussion with the FDA where the medical device company describes the technology and the status of its feasibility or validation work and asks questions about the amount of data it must develop for submission to FDA,” says Anastasi. During the meeting, FDA provides input and guidance on the collection of data from the clinical studies. For significant risk devices, a company will be required to submit an IDE, (Investigational Device Exemption) submission prior to beginning any clinical studies. Devices that are deemed “non-significant risk” do not require submission of an IDE. The clinical studies are then performed. When the study is complete, the medical device company will submit the appropriate 510(K) or PMA to FDA.
In terms of other medical device regulatory studies, medical device CROs also perform component testing and biocompatibility/safety testing, i.e. the ISO-10993-dictated package that comprises materials evaluation and biocompatibility testing up through advanced animal models. Glenn J. Smits, PhD, director of the discovery center at MPI Research, a preclinical CRO located in Mattawan, Mich. that provides Medical Device Evaluation services and performs ISO-10993 testing, explains the concept of biocompatibility: "Let's say that a company is developing a bandage and they change the polymers or the chemical constituents of the glue that sticks to your skin. If there is a specific new chemical that they are putting in that material, it has to be evaluated for tissue reactivity, i.e. if it irritates the skin, it's not biocompatible," he says. "Any medical device and each component/chemical that comprise the device that essentially makes it to application in humans has to go through this ISO-10993 package of studies to demonstrate its safety," says Smits.
The studies that comprise the ISO-10993 package are essentially a set of toxicological and biocompatibility assessments—often referred to as a six pack or eight pack—such as tissue and skin sensitivity, irritancy tests, acute subcutaneous implant, etc. As mentioned above, the determination of which tests to run is based on the device category (Class I, Class II, or Class III), where the device contacts the body, and the duration of this contact. There are eight specific studies in the Initial Evaluation Tests, including cytotoxicity, sensitization, irritation or intramuscular reactivity, systemic acute toxicity, genotoxicity, biocompatibility of the implant, and hemocompatibility. There are four Supplemental Evaluation Tests that may be appropriate: chronic toxicity, carcinogenicity, reproductive/developmental toxicity, and biodegradability. These studies focus solely on the safety of the biomaterial/medical device, and thus are specialized toxicological studies.
Trends
In addition to changes in regulatory guidelines, there have also been several noticeable trends in the medical device and medical device CRO industries. "In terms of trends, over the last five years, we have seen an increase in the number of small, highly specialized medical device CROs," says Smits. Some of these specialized "shops" may only consult on cardiovascular devices, while others might be focused on orthopedic devices. Some specialize in running the ISO-10993 studies mentioned earlier. In contrast, MPI research is a broad-based medical device CRO covering multiple therapeutic areas, spanning the initial ISO-10993 evaluations through to short-term and long-term safety and efficacy studies of the final device in advanced animal models.
“One major trend we are seeing in our industry is an increase in medical devices and diagnostic products used in the treatment and diagnosis of diabetes,” says Anastasi, who adds that there is also an increase in devices and diagnostic products in therapeutic areas that are related to the downstream effects of diabetes, such as wound care, podiatry, and ophthalmics. Finally, according to Anastasi, another large area of growth is in the area of Companion Diagnostics; she adds that MDCI also consults in this area. “As a result of this trend, we have seen an increase in the number of pharmaceutical firms entering the medical device space in the last two years,” says Anastasi.
In summary, medical device CROs are a necessary partner in this highly regulated industry.
Check out our Medical Device CRO section for more information or to find companies that provide these services.