FDA Reclassifies IVDMIA

After much consternation on the part of the nascent genomic profiling industry, the FDA has (re)classified a gene expression test system for breast cancer prognosis from a Class III to a Class II medical device. When the Dutch company Agendia first applied to the FDA for approval of their MammaPrint test, they received a Class III designation by default. Class III requires premarket approval which would significantly increase the costs of developing these systems. Agendia petitioned the FDA for a lower classification and the FDA came back last week with the lower Class II designation. Class II requires the developer to file a 510(k) premarket notification that complies with the FDA's special controls guidance document.

MammaPrint is the first In Vitro Diagnostic Multivariate Integrating Assay (IVDMIA) to be approved by the FDA for the prognosis of breast cancer. These are a new breed of genomic profiling assays that offer the promise of personalized medicine and improvements in diagnosis and treatment.

Designation of these tests as Class III devices would seriously hamper the progress of this industry by increasing the regulatory costs. As a Class II device however, the FDA has reduced the regulatory burden but has still retained certain special controls such as a description of the algorithm used to analyze the results as well as a description of how the algorithm was derived.

This is critical since the algorithms are both the key ingredient in the tests and are proprietary. Without this control, there is no way of asserting the validity of the tests.

Although the FDA has indicated that a number of tests have been cleared as Class II devices for other tumors, this guidance has only been extended to IVDMIAs that apply to breast cancer prognostic tests. This may serve as a model for other IVDMIAs to be developed for other diseases in the future.

PGx Industry vs FDA: Round 1

Apparently things weren't quite as sanguine at the FDA's public hearing on IVDMIAs as they had hoped. The pharmacogenomic industry turned out to roundly criticize the FDA's draft guidance document. Comments seemed to focus on the fact that this is a fledgling industry and requires some leeway in order to grow, leeway that may be restricted should the FDA require the diagnostic tests go through a regulatory process. On the one hand, the FDA claims that although the components of the tests may all be approved, they have not been approved as a system and thus are considered a new devise. Because the tests cannot be analyzed outside of their proprietary kit, the results cannot be evaluated independently and thus are essentially black boxes; the consumer or physician using the test must rely completely on the authority of the manufacturer.

The PGx industry sees their costs sky rocketing if the FDA gets involved not to mention increasing time to market. Along with rising costs come rising risks; not only will the regulatory process cost more, there is an increased chance that the test will not be approved at the end of the process.

Some of this risk could be reduced if the FDA could streamline their process. This is a very dynamic field that could be of great help in both improving health and lowering costs in healthcare. This comes straight up against a government bureaucracy and the fear is that progress will be slowed to a crawl. The FDA has been charged with protecting the public's health but could they be hurting it in the process?

21st Century Medicine

On the eve of the FDA's public hearing on their draft guidance on in vitro diagnostic multivariate index assays (IVDMIAs) a group comprised of molecular diagnostic companies and investors known as The Coalition for 21st Century Medicine has asked the FDA to follow a more formal process in determining the future of this promising technology. What is being considered here is whether IVDMIAs may be subject to FDA regulation and if so, which ones and how much. Added regulation means added resources, resources that could be spent on further research and development and expansion of technologies that are still very much in a nascent stage. These are the early days of personalized medicine, a time in the life cycle of a technology where a significant investment is required to make headway. The added burden of regulation may present a set back to the industry just when businesses were beginning to show some returns.

Although regulation of IVDMIAs is inevitable, requiring the FDA to go through a more formal process before initiating regulation will buy some time, time to bring more products into the market, gain more credibility with the insurance companies and bring a greater return to investors before the added costs of regulation come into play.