GAITHERSBURG, Md. (GenomeWeb News) — At a public meeting convened by the US Food and Drug Administration yesterday, health-care interest groups and industry stakeholders blasted an agency draft guidance that would have the FDA regulate what it calls in vitro diagnostic multivariate index assays, or IVDMIAs.
In more than 30 presentations, stakeholders claimed that the "Draft Guidance for Industry, Clinical Laboratories, and FDA Staff – In Vitro Diagnostic Multivariate Index Assays," in its current form, is untenable, even potentially illegal.
Presenters criticized that the document fails to clearly define what the FDA considers IVDMIA’s; does not explain how the agency’s regulations would dove-tail with CMS’ Clinical Laboratory Improvement Amendments guidelines; and would become a disincentive to innovation in personalized medicine.
As GenomeWeb News reported last fall, the FDA defined IVDMIAs as tests that use mathematical formulas to interpret gene and protein data to guide medical decision-making. In the guidance, the FDA said such tests, ordinarily overseen by CLIA regulations, must instead be cleared by the agency due to their complexity.
The public has until March 5 to submit formal comments about the draft, which can be read here.
Several presenters at the meeting suggested that the FDA has no legal authority to regulate IVDMIAs, while others suggested that the agency rescind the draft altogether and proceed through formal rulemaking procedures.
To these comments, Steven Gutman, director of the Office of In Vitro Diagnostic Device Evaluation, responded that the FDA “always expected that the document was not perfect and I guess you have suggested the same.
“As we were interacting with people in the early life of the document, I thought that people were either over-reading or misreading the document,” Gutman said. “So, I was blaming you, not us, but I will take part of the blame perhaps for not having crafted language that clearly. …
“We didn’t think that this was going to be easy,” he added. “And you reinforced that.”
Some in the industry have organized themselves to petition the FDA more effectively. Yesterday, a group calling itself the Coalition for 21st Century Medicine said it was created to ask the FDA to consider altering its IVDMIA plans.
Sharon Terry, CEO of Genetic Alliance, is one member of the group, which comprises genomic, proteomic, and molecular diagnostic companies and investors. Speaking at the meeting yesterday, she said that the “existing industrialized manufacturing regulatory model of the 19th Century will not lay over well in the new era of personalized medicine. We want federal authorities to be looking forward to this new age.
“We stand at the tipping point of dramatic and powerful advances and understanding and potential management of these disease pathways, and the regulatory pathway can either promote or stymie innovation, access, affordability, and transparency,” she told the meeting. “So, we feel that this guidance fails to adequately deal with this dynamic reality and in our community a great deal is at stake. We feel we really need to get this right, now.”
She said that the guidance should be “withdrawn and that a formal rulemaking process be initiated.” She also asked that “a formal public engagement initiated to be established [within] HHS [and] across the federal agencies involved in this, and establish a process that will deliver a regulatory pathway that will enable 21st century healthcare.”
Mara Aspinall, president of Genzyme Genetics and also a member of the coalition, suggested that the FDA set up “an additional meeting before proceeding further with an independent third party. … A session that’s a workshop, or of a similar format, where true interactive dialogue can occur,” she said.
“In every case, it is the treating physician that makes the choice about which validated test is appropriate for a particular patient and to ensure that each test is medically necessary,” Aspinall said. “Unless and until a new diagnostic test reaches a critical and relatively large volume no commercial test kit can be developed.
“Lacking that critical volume there is no market incentive to develop a kit and to spend the resources required to take this kit through a full FDA process,” she said. “The bottom line, as a result for conditions that effect relatively small number of patients, or more importantly in oncology and infectious disease, subpopulations of patients, the only access to valuable and necessary testing is through laboratory developed tests.”
A common criticism among presenters was that draft guidelines are “technology based” and not “risk based.” But Daniel Schultz, director of FDA’s Center for Device and Radiological Health, maintained that “this couldn’t be further from the truth,” and said presenters had misinterpreted the agency’s intent.
“At the end of the day, what we are very, very interested in is providing a regulatory oversight framework that does in fact reflect the risk of the product,” Schultz said. “I will say to some extent — and perhaps we can do a better job of defining this — but there is a link between the changes in technology and the level of risk. We need to explain that. If you don’t understand it then we haven’t succeeded.”
Gutman urged presenters to offer constructive comments on the draft guidance by the March 5 deadline and asserted that it is not the agency’s intent to “surprise or confuse people” or issue regulations that would delay the entry of innovative products to the market.
Sensing growing interest in this area, the FDA last year extended by 90 days the original Jan. 5 deadline for comment. Gutman also noted that the agency has been clear in expressing its discomfort over the lack of federal oversight of IVDMIAs.
“The idea that we can simply go back to the way we were several months ago, that to me is the one notion that would be unacceptable,” Schultz noted at the meeting.
“The field is moving very quickly, the technology is moving very quickly, expectations in this room and throughout the country are moving very quickly in terms of us being able to get a handle on this type of technology,” he said. “I think we need to keep moving forward based on today’s discussion.”
The meeting took place two days after the FDA announced it has cleared the first-ever IVDMIA, a breast cancer-recurrence test made by Belgium diagnostic company Agendia.
As GenomeWeb News reported yesterday, the agency said Agendia had submitted data from tumor sample studies from 302 European patients as evidence that the test was “validated for its intended use.”
The FDA said these data “sufficiently confirmed that Agendia’s test could be used to predict “time to distant metastasis” in women aged 61 years and younger, in some women with early stage breast cancer, and in some women with tumors less then five centimeters.
"There have been rapid advances in microarrays and other pioneering diagnostics, and a corresponding increase in the use and impact of these complex tests,” Gutman said in a statement at the time. “This has prompted FDA to take a closer look at the potential risks as well as the benefits associated with such tests when they are developed and used in laboratories.”
"There have been rapid advances in microarrays and other pioneering diagnostics, and a corresponding increase in the use and impact of these complex tests,” Gutman said in a statement at the time. “This has prompted FDA to take a closer look at the potential risks as well as the benefits associated with such tests when they are developed and used in laboratories.”
He said the MammaPrint clearance “takes into account the development of these innovative technologies and ensures public health by carefully evaluating their performance."
"Clearance of the MammaPrint test marks a step forward in the initiative to bring molecular-based medicine into current practice," FDA Commissioner Andrew von Eschenbach said in the statement.
"Clearance of the MammaPrint test marks a step forward in the initiative to bring molecular-based medicine into current practice," FDA Commissioner Andrew von Eschenbach said in the statement.