TRENDS & PERSPECTIVES
FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) held a public meeting on its draft guidance for in vitro diagnostic multivariate index assays (IVDMIA). During this meeting, OIVD heard presentations and comments from interested stakeholders regarding the draft IVDMIA guidance.
While many of the speakers were generally supportive of FDA’s aims and objectives, they believed that the draft IVDMIA guidance needs to be improved in a number of respects. For example, the speakers agreed that the draft guidance is not clear enough in areas such as the actual definition of an IVDMIA. Another concern that was cited is the absence of guidance on the interplay between the quality system regulation (QSR) for IVD manufacturers and the requirements under the Clinical Laboratory Improvement Amendments (CLIA) for laboratories, and how any differences could be reconciled.
“There is scant detail provided in the draft guidance, making compliance with its requirements difficult,” said Gail Javitt, JD, of the Genetics and Public Policy Center at Johns Hopkins University (Baltimore). “FDA should provide clear, transparent directions regarding its expectations. The definition of IVDMIA is itself quite fuzzy, leaving some to wonder whether their tests are or are not IVDMIAs. While FDA invites questions, we believe a clearer articulation of what tests do and do not fall within the IVDMIA scope would alleviate current confusion.
“Additionally, FDA has provided little concrete direction regarding how its QSR regulations will interact with the CLIA requirements. FDA should quickly issue clarifying guidance to avoid subjecting laboratories to duplicative and potentially conflicting requirements.”
A number of speakers also expressed concerns about the impact of the draft IVDMIA guidance on innovation, both for developing new tests and improving existing tests. The speakers were concerned that FDA intrusion into the regulation of labs will delay or jeopardize the development of new IVD tests and technologies.
“In its current form, the draft guidance will significantly affect the ability and incentives for clinical labs to develop new diagnostic test services that build on current medical knowledge,” said Tom Tsakeris, who spoke on behalf of the Coalition for 21st Century Medicine (Arlington, VA). “The draft guidance extends the scope of FDA regulation to IVDMIAs on the premise that IVDMIA test results ‘cannot be interpreted by the well-trained health care practitioner using prior knowledge of medicine without information from the test developer regarding its clinical performance and effectiveness.’
“On the contrary, FDA should be clear that the primary incentive for clinical labs to develop new diagnostic testing capabilities derives from the demand from physicians to obtain new innovative testing services commensurate with their advancing knowledge of the potential usefulness of such testing, and not vice versa. Subjecting clinical labs to the added burden of complying with FDA regulatory requirements will result in physicians and patients experiencing either unnecessary delay or doing without access to important tests in rapidly advancing fields.”
In addition, many of the speakers criticized the draft IVDMIA guidance for being technology-based and not risk-based. However, in his closing remarks, Daniel Schultz, director of FDA’s Center for Devices and Radiological Health, said that this could not be “further from the truth” concerning the agency’s objectives, based on internal discussions. This difference underscores the gap between FDA’s intentions and the actual content of the draft guidance as interpreted by third parties.
“FDA appears to have adopted a purely technology-based approach to the regulation of laboratory-developed tests,” said Javitt. “While FDA states that, within the category of IVDMIAs, its approach will be risk-based, its initial distinction between IVDMIAs and non-IVDMIAs does not appear to be risk-based. By separating IVDMIAs from all other laboratory tests, FDA seems to be operating under the assumption that IVDMIAs are, as a class, inherently higher in risk than other laboratory tests. While certain intended uses of IVDMIAs will no doubt put them in an elevated-risk category, we are concerned that FDA’s piecemeal approach overlooks other high-risk tests that do not fall within the IVDMIA framework, while at the same time inappropriately categorizing all IVDMIAs as inherently more risky than other diagnostic tests, based on the technology used.”
OIVD officials declined to provide any further detail or concrete insights as to how the meeting will affect the draft IVDMIA guidance.
“We learned that there is a lot of very passionate interest in this, that there are a lot of very interesting and important ideas to put on the table, and that we need to be very careful on how we move forward,” said Steven I. Gutman, MD, director of OIVD. “But we are also very interested when the comment period closes on March 5 in seeing perhaps a broader array of comments that may reiterate, reinforce, or supplement. We have to sort through all of the comments and take them very seriously in terms of directing what to do next. We have to deliberately consider how does the agency weigh these ideas, and what is the impact on future policy.”
Additional information about the meeting can be accessed via the OIVD Web site at www.fda.gov/cdrh/oivd/meetings/020807agenda.html. A copy of the draft IVDMIA guidance can also be accessed at www.fda.gov/cdrh/oivd/guidance/1610.html.
