Barbara Conley, Associate Director of the Cancer Diagnosis Program at the NCI Division of Cancer Treatment and Diagnosis, explained that the risk-based approach is not designed to lower overall standards but to focus on those activities that prevent or mitigate risks related to the diagnostic product, an idea that was reiterated throughout the forum.

Moderator Howard Scher, Chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center, presented two proposals: first, that co-Dx designed for a drug with the breakthrough designation be automatically eligible for priority review and second, that highly coordinated administrative processes and management commitments, similar to those offered with the breakthrough designation for drugs, be used for the review of IVD co-Dx associated with breakthrough therapies.

(L-R) Howard Scher, Barbara Conley, Tracy Bush, Christine Gathers, Mike Pacanowski, and Liz Mansfield 

Tracy Bush, Director of Companion Diagnostic Regulatory Affairs for Roche Diagnostics, presented two proposals involving the application of a risk-based approach. The first uses the approach to determine the co-Dx analytical studies required, dependent on assay type, for PMA filing, and the second looks at the requirements for quality systems, manufacturing processes, and software testing and documentation.

Christine Gathers, Senior Director of Regulatory Affairs for Diagnostics at Eli Lilly and Company, discussed the panel’s final proposal, a “Continued Access” supplement IDE that will allow labs that do not participate in a trial to get experience with a new diagnostic system earlier and faster, allowing for broader commercial availability.

Two panelists representing FDA, Mike Pacanowski, Associate Director of Genomics and Targeted Therapy at the Center for Drug Evaluation and Research’s (CDER’s) Office of Clinical Pharmacology, and Liz Mansfield, Director of the Personalized Medicine Staff at the Center for Devices and Radiological Health (CDRH), responded to these proposals.

Liz Mansfield
Dr. Packanowski commended the proposals, stressing the importance of efficient planning in diagnostic development and increased communication between sponsors and FDA. Dr. Mansfield mentioned that CDRH does prioritize co-Dx, and they do receive priority review. She stated that the administrative suggestions seem quite doable, and she liked the risk-based approach and suggestions towards identifying potential improvements to co-Dx development efficiency. Dr. Mansfield also mentioned that the biggest hurdle in the process may be Quality Systems Regulations.

After the presentation, Liz Mansfield also highlighted that FDA understands how co-Dx are affecting drug development and regulation and that CDRH and CDER are working extremely closely to discuss new and innovative approaches. Keith Flaherty pointed out that one concern about the Breakthrough Designation is the potential strain on FDA caused by an “all hands on deck” philosophy towards those products, especially given the large number of applications that have been received. Jeff Shuren, the Director of CDRH, acknowledged that limited resources present a challenge.

The second panel, “Policy and Practices to Facilitate Personalized Medicine,” moderated by Senior Nature Medicine News Editor Elie Dolgin, responded to Panel One’s proposals and provided perspectives regarding the opportunities and challenges that exist around co-Dx development and the implementation of “precision medicine.” Highlighted topics included the growing role of molecular diagnostics in medicine, how reimbursement for co-Dx is being approached by insurance companies, and the role databases and registries may play in improving drug development.

Jeff Shuren, Director of CDRH, stated that CDRH is working on formalizing a policy shifting certain pre-market requirements to post-market, much like the accelerated approval process for drug development. He also reiterated FDA’s support for the suggestions proposed by Panel One, stating, “What is coming out of the recommendations today from the white paper are considerations we would look to potentially fold into [a] draft policy.”  When asked about the need for additional legislation, Dr. Shuren said that although it could be helpful, there’s a lot the CDRH can do with its current authority.

Janet Woodcock, Director of CDER, mentioned her hope that Breakthrough would expand from targeted, genetic diseases, like cancers, to resistant bacterial infections. Bill Chin, PhRMA’s Executive Vice President for Science and Regulatory Affairs, commented that someday all drugs should be breakthroughs, but this has not yet been possible because our current understanding of disease is so limited.

(L-R) Elie Dolgin, Janet Woodcock, Bill Chin

Keith Flaherty, Director of the Henri and Belinda Termeer Center for Targeted Therapies at the Massachusetts General Hospital Cancer Center, brought up the role of payers in a landscape where many diagnostic markers are still exploratory.

Matt Zubiller, Vice President of Decision Management for McKesson Health Solutions, explained McKesson’s attempts to develop a new coding system for insurance forms that will determine the value of different diagnostic tests being used and identify the clinical utility of the tests. Diagnostic tests are not currently reimbursed based on value, but pharmacy benefit and medical benefit should be important considerations in diagnostic reimbursement.

A discussion ensued about the decision-making process in determining treatment and the role that cost plays in those decisions. Michael Kolodziej, National Medical Director of Oncology Solutions at Aetna, pointed out that as more choices of drugs and treatments are available at multiple prices, coverage decisions will have to be made based on that. Kolodziej stressed the need for more effective treatment as well as the benefits of co-Dx, stating, “We have to find the way to get the right drug to the right patient.”

Keith Flaherty mentioned the inefficiency of unused data collected in clinical trials. Although the current weaknesses in databases and registries was acknowledged, it was pointed out that diagnostic and drug development will benefit from shared investment and academics and industry will have to compromise to share data and improve trial designs. Bill Chin stressed the importance of balancing rigor with innovative science.

Panel One: Development Strategies for Breakthrough Therapy Diagnostics

A Risk-based Approach for In Vitro Companion Diagnostics Device FDA Approval Process Associated with Therapies that have Breakthrough Designation (September 2013)