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FDA Forms Working Group to Push Ahead Stalled Rx/Dx Guidance Plans

The US Food and Drug Administration has convened a working group to advance a long-planned guidance document on the co-development of drug and diagnostic products, a high ranking agency official announced last week at a personalized medicine conference sponsored by the Harvard-Partners Healthcare Center for Genetics and Genomics in Boston.
The multi-center and multi-disciplinary working group has met once to discuss potential guidance on Rx/Dx co-development, and plans to meet again in early December, Lawrence Lesko, director of FDA’s Office of Clinical Pharmacology, told Pharmacogenomics Reporter this week.  
The agency has long discussed its intent to issue guidelines on the regulatory framework for developing companion diagnostics, which many believe are integral to the advancement of personalized medicine. However, since issuing a white paper in 2005 on the topic, the agency has made little progress in the way of issuing formal guidelines.
FDA officials had originally announced plans to issue a draft guidance on Rx/Dx co-development by the end of last year. When the guidance did not materialize by November 2007, the agency pushed back the deadline to mid- to late-2008. Over this year, the agency has discussed its intent to issue such a guidance, but until now has not provided any updates on the progress it is making.
Lesko did not say when a guidance would appear.
“It is much too early to discuss whether or not a public meeting will be held or even a timeline for the draft guidance,” Lesko said in an e-mail. “FDA recognizes the urgency of moving forward with this guidance and is committed to do so.”
‘Enough Experience’
Industry observers agree that existing incentives, development timelines, and regulatory procedures discourage the kind of collaboration necessary for drug and diagnostic co-development.
There are legislative efforts underway in Congress that seek to incentivize the advancement of personalized medicine, specifically the development of companion diagnostics [see PGx Reporter 09-17-2008].
However, drug and diagnostic makers have been awaiting guidance from the FDA on how combination products will be regulated since it requires that two FDA divisions — its Center for Drug Evaluation and ResearchandtheCenter for Devices and Radiological Health — work together. In addition, the regulatory environment for laboratory-developed tests is rapidly evolving.  
In previous comments, Lesko has suggested that rushing to regulate Rx/Dx co-development could potentially stifle innovation in the nascent field [see PGx Reporter 06-20-2007]. 

“We hope that FDA considers that process when developing the guidance for co-developed products.”

“Guidance for industry issued prematurely and without enough regulatory experience can potentially be a barrier to innovation of a rapidly evolving science,” Lesko reiterated to Pharmacogenomics Reporter last week. As an example, he pointed out that although industry has for years asked for guidance on adaptive clinical trials, “only now has FDA gained enough experience to draft a guidance, which it is working on.”
Similarly, the agency has been slowly building up its regulatory experience on Rx/Dx co-development through several projects currently underway. Last year, the agency took steps to develop performance standards for evaluating Rx/Dx co-submissions using as a model Ventana’s application to the FDA for a lung cancer assay. The Critical Path Institute will use a $2.1 million Arizona state grant to shepherd the diagnostic maker through the FDA’s regulatory submissions process, which is meant to serve as a guide for future co-submissions [see PGx Reporter 10-17-2007].  
Likewise, last year, Ocimum BioSolutions subsidiary Gene Logic entered into a collaboration with the FDA in which the company will submit quality-control metrics and work with FDA officials across its divisions to improve the agency’s understanding of microarray-based genomic data that companies submit as part of their regulatory submissions [see PGx Reporter 09-19-2007].
The agency has gained more clarity on the types of genomic data drug companies need to submit as part of new drug applications through its Voluntary Genomic Data Submissions program. Launched in 2004, VGDS has received genetic information on more than 50 drugs [see PGx Reporter 11-29-2006].
Stakeholder Input
Since the regulatory environment for laboratory-developed tests is currently in flux, the agency should consider input from stakeholders before issuing a guidance on Rx/Dx codevelopment, according to one non-profit focused on advancing personalized medicine.  
The IVDMIA draft guidance that the FDA released in 2006 “caused a lot of concern in the field,” Amy Miller, public policy director for the Personalized Medicine Coalition, told Pharmacogenomics Reporter this week. “We hope that FDA considers that process when developing the guidance for co-developed products.” The PMC’s members include pharmaceutical, biotech, and diagnostic companies, clinical laboratory testing services, governmental agencies, insurance companies, and patient advocacy groups.
After releasing the first IVDMIA draft document, the FDA held a public meeting during which many laboratory test developers claimed that the agency’s intent to regulate this subset of lab-developed tests would hinder innovation, fall outside the agency’s regulatory purview, and is confusing.
After that meeting, the FDA issued a second draft guidance with which many stakeholders took issue for similar reasons. The agency has not provided a timeline for when it plans to issue a final IVDMIA guidance.
What is clear in the industry is that FDA’s final stance on IVDMIAs will have significant implications for the development of Rx/Dx combination products. Given the high cost of diagnostics development and the relatively narrow margins, some lab-test makers are concerned that increased oversight and lengthy FDA reviews, particularly with regard to IVDMIAs, will stymie the development of diagnostics for rare diseases [see PGx Reporter 02-14-07].
Meanwhile, others have noted that FDA approval of genetic tests may give big drug makers additional confidence in the accuracy of the diagnostics, which in turn may encourage them to use the tests to help them develop pharmacogenomics-based targeted drugs [see PGx Reporter 05-30-07].
“FDA should consider companion diagnostic guidance development as a very high priority, and we urge them to develop it in the most transparent and collaborative way that law allows,” Miller said.

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