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Margaret Hamburg, M.D.
Commissioner
Food and Drug Administration
10903 New Hampshire Ave.
Silver Spring, MD 20993

RE: Docket No. FDA-2011-D-0215
Draft Guidance for Industry and Food and Drug Administration Staff:  In Vitro Companion Diagnostic Devices

Filed electronically at http://www.regulations.gov

Dear Dr. Hamburg:

The National Coalition for Cancer Survivorship (NCCS), representing survivors of all forms of cancer, is pleased to comment on the draft guidance document related to in vitro companion diagnostic devices.  We agree with the fundamental goal of encouraging the contemporaneous development and review of diagnostics and drugs, if the diagnostic provides important information about the population of individuals who might benefit from the drug, the populations that may not benefit or be harmed, and the optimal means for monitoring adverse events associated with the drug. However, we believe the draft guidance falls short in several ways in protecting the needs of patients.

Cancer patients have great hopes and expectations for the development of targeted therapies, including diagnostics that would guide their use.  Patients have expressed their commitment to this process by participating in clinical trials testing targeted therapies and by other actions to support research and development of such treatments.  We agree with the underlying principle of the draft guidance that diagnostic tests must have clinical utility and validity.

The draft guidance fails patients and developers of drugs and diagnostics because it does not provide a clear regulatory pathway for companion drugs and diagnostics.  This failure relates in part to the lack of clarity about the treatment of laboratory-developed tests (LDTs).  Specifically, it is not clear if the draft guidance covers LDTs that will guide decisions about targeted treatments, thereby requiring them to pursue a premarket application (PMA) or 510(k).  At the Food and Drug Administration (FDA) public workshop on LDTs on July 19-20, 2010, the agency indicated it was reconsidering its enforcement discretion related to LDTs.  FDA suggested that the risks of LDTs had changed, as patients were increasingly relying on LDTs to guide treatment, and that increased regulation was necessary.  We assume that LDTs that will guide decisions about targeted treatments would be covered by the draft guidance. However, if LDTs, a significant group of diagnostics that might relate to decisions about the utilization of life-saving therapies, are not subject to the draft guidance, the guidance will have failed to meet the fundamental goal of ensuring the proper targeting of a new class of treatments. In addition, the lack of clarity about LDTs means that sponsors do not have certainty about the regulatory pathway for co-development of drugs and diagnostics. 

In addition, this draft guidance does not create a level playing field for the development of important diagnostic tests to be used in targeted therapeutic decision-making.  Some sponsors may be subject to FDA regulation while others may still be governed by the standards of the Clinical Laboratory Improvement Act (CLIA).

The lack of clarity and certainty around the diagnostic regulatory process could affect the efficiency and speed of review of targeted therapies, as the draft guidance requires contemporaneous review of the drug and related diagnostic.  While the guidance makes an exception to this requirement for contemporaneous review, this solution is unsatisfactory as it could create a cumbersome exceptions process and does not replace the need to address shortcomings in the review process for diagnostics for targeted therapies.  The draft guidance excepts those cases where the treatment “is intended to treat a serious or life-threatening condition for which no satisfactory alternative treatment exists and the benefits from the use of the therapeutic product with an unapproved or uncleared IVD companion diagnostic device are so pronounced as to outweigh the risks from the lack of an approved or cleared IVD companion diagnostic device.”  Even though this exception would likely apply to most, if not all, cancer therapies, we would urge instead that the agency clarify, and ensure a level playing field for, the review process for diagnostics for targeted therapies.

Thank you for the opportunity to comment.