Trends & Perspectives

Published: November 2, 2011
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FDA releases guidance on companion diagnostics

FDA released its draft guidance on in vitro companion diagnostic devices. The guidance is intended to assist companies that are planning to develop a drug that depends on the use of a companion diagnostic for its safe and effective use as well as those companies that are planning to develop a companion diagnostic that is intended to be used with a corresponding drug.

By: Richard Park

FDA has released a draft guidance on companion diagnostics regulationFDA released its draft guidance on in vitro companion diagnostic devices. The guidance is intended to assist companies that are planning to develop a drug that depends on the use of a companion diagnostic for its safe and effective use as well as those companies that are planning to develop a companion diagnostic that is intended to be used with a corresponding drug. Industry analysts were positive in their overall assessments of the guidance.
“The draft guidance is helpful in several respects by clarifying or reinforcing some key regulatory aspects,” said Jeffrey N. Gibbs, JD, a director at Hyman, Phelps & McNamara (Washington, DC). “The document highlights the increasing importance diagnostics will be playing in the drug approval process. It also underscores the need for IVD and drug companies to work together at an earlier stage and more collaboratively than they historically have done. The document will act as a wake up call to pharmaceutical companies that they need to incorporate IVDs into their clinical and regulatory strategies.”
“I generally like this guidance document as far as it goes,” said Bradley M. Thompson, JD, an attorney at Epstein Becker Green (Washington, DC). “It represents a positive evolution in FDA’s thinking, in which theory is starting to meet reality. The agency has tried to acknowledge that co-development of therapeutic drugs and diagnostic devices proceeds in lots of different ways, often far from the theoretical and idealized approach of lockstep development.”
However, analysts were also critical of the draft guidance, particularly the lack of details in the document.
“The draft guidance leaves many questions open as to exactly how this regulatory process will unfold,” said Gibbs. “It is short on details. In addition, it doesn’t address some major issues that are inherent in the current regulatory process. For example, it says that labeling for an approved IVD should be expanded if ‘evidence becomes available that use of the same device is essential’ for another drug. But given the delays built in to the premarket approval (PMA) and new drug application (NDA) processes, implementing the labeling change will occur well after the information is recognized as ‘essential.’
“Similarly, the companion diagnostics document doesn’t address the problems created by the discovery of clinically new mutations or deletions during the clinical study or regulatory review process and how to incorporate that information into the approved labeling.”
“The problem is that the document is thin,” said Thompson. “Influenced no doubt by the sheer complexity of the number of possible scenarios for co-development, FDA chose to stay at a very high principled level. The agency really doesn’t get its hands dirty dealing with the more nitty-gritty regulatory questions. The problem is that’s where the challenges are.
“I know that a number of companies have expressed specific questions to the agency to deal with the more tactical issues. While FDA can’t address everything, it seems to me the agency ought to spend a little more time trying to address the questions that they are hearing most often at a granular level. Such topics might include the following: the use of bridging or concordance studies to link clinical data with older versions of an assay used in previous clinical studies; specific regulatory pathways for specific scenarios (i.e., When is a PMA required instead of premarket notification?); and details around the type of analytical study package necessary to support clinical testing of an IVD.”
“There are several opportunities for improvement or expansion in the draft guidance,” said Fred Lasky, PhD, principal consultant at Lasky Consulting. “First, a major challenge with sponsors is how to determine appropriate test design to bridge a diagnostic from use during clinical trials (using good laboratory practices) to one that is capable of receiving clearance or approval by FDA. The question is when a test has been used in a pivotal drug trial, how much additional work is necessary to demonstrate that it is safe and effective.
“Second, FDA acknowledges that not all tests that are useful in therapeutic dosing or monitoring should be considered companion diagnostics. But the examples given in the guidance are tests that have been available for decades. It would be helpful to describe the considerations for a companion diagnostic in terms of physiological or pathological outcomes that are general or specific to a drug. This might also help determine which companion diagnostics would be class II versus class III devices.
“Third, if a diagnostic requires an investigational device exemption (IDE), FDA should consider an approach that couples the medical device IDE requirements with drug NDA requirements. It should make the clinical trial designs easier and add efficiency for the sponsors and the agency.
“Fourth, various issues and questions will emerge when a second generation or competitor of a companion diagnostic is being prepared for market. For example, will the requirements for approval be identical? What might be needed if the second device is not developed or partnered with a therapeutic company? How specific should the labeling be for the drug and the IVD device? Can an IVD device be identified in the drug labeling in a clear, generic description that ensures only approved devices are used for patient evaluation or monitoring?”

Note: IVD Technology is producing a Webcast on this subject, which will air on November 10th. The speaker is Dr. Elizabeth Mansfield, PhD, the Director of the Personalized Medicine Staff at FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD).
 


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