Assessing FDA’s Final Guidance on Companion Diagnostics
On the same day that FDA released its draft guidances on regulating laboratory-developed tests (LDT), the agency also issued a final guidance on the development, review, and clearance of companion diagnostics. According to FDA, this guidance is intended to help companies identify the need for these tests during the earliest stages of drug development and to plan for the development of a drug and a companion test at the same time. The guidance’s ultimate goal is to stimulate early collaborations that will result in faster access to promising new treatments for patients living with serious and life-threatening diseases. The guidance finalizes and takes into consideration public comments on the draft guidance that FDA issued in 2011.
“Ensuring that doctors and patients have access to safe, accurate, and reliable diagnostic tests to help guide treatment decisions is a priority for the FDA,” said FDA Commissioner Margaret A. Hamburg, MD. “Inaccurate test results could cause patients to seek unnecessary treatment or delay and sometimes forgo treatment altogether. This action demonstrates the agency’s commitment to personalized medicine, which depends on accurate and reliable tests to get the right treatment to the right patient.”
I asked several attorneys who have followed the regulation of companion diagnostics for their analysis and opinions on FDA’s final guidance on companion diagnostics. Jamie K. Wolszon, an associate attorney at Hyman, Phelps & McNamara, said that while the final guidance is very similar to the draft guidance, a few points in the final guidance are worth noting.
Wolszon believes that FDA provided helpful clarification as to what constitutes “essential” in footnote 6 of the final guidance:
When use of a diagnostic device is required in the labeling of a therapeutic product (e.g., for selection of appropriate patients for therapy, or to select patients who should not use the product, or for monitoring patients to achieve safety or effectiveness), use of the diagnostic device is considered “essential” for the purposes of this guidance. Uses of diagnostic devices that are suggested but not required in therapeutic product labeling are not considered “essential.”
As for differences between the final and draft guidances, Wolszon said that one issue relates to FDA’s position regarding combination products. In footnote 5 of the final guidance, the agency stated the following:
FDA expects that most therapeutic product and IVD companion diagnostic device pairs will not meet the definition of “combination product” under 21 CFR 3.2(e). It is not necessary to contact the Office of Combination Products about whether a therapeutic product and IVD companion diagnostic device pair is a combination product unless recommended by CDER, CBER, or CDRH. FDA intends to require separate marketing applications for a therapeutic product and an IVD companion diagnostic device intended for use with that therapeutic product regardless of whether the products could constitute a combination product. The standards for review, approval, or clearance would be the same whether or not the therapeutic product and the IVD companion diagnostic device pair were considered a combination product.
“Essentially, FDA appears to be saying that even if the products could constitute a combination product, the agency is still going to want separate marketing applications for a therapeutic product and an IVD companion diagnostic device,” said Wolszon.
Wolszon added that this language on combination products in the final guidance appears to be considerably stronger than the language in footnote 4 of the draft guidance, which reads as follows:
To the extent an IVD companion diagnostic device and a therapeutic product together meet the definition of a combination product, a single application for the combination product may be submitted in some cases, though where appropriate, and the Agency may require separate applications for the constituent parts of the combination product.
Jonathan S. Kahan, a partner at Hogan Lovells, said the final guidance is consistent with and reiterates FDA positions regarding companion diagnostics, which the agency outlined and informally enforced since it issued the draft guidance in 2011. During that time, FDA has been working with sponsors of therapeutic product/diagnostic test combinations on a case-by-case basis, and based on the final guidance document, it appears likely the agency will continue to do so.
“Industry and the agency have acknowledged that companion diagnostics are critical to the advancement of personalized medicine,” said Kahan. “However, given the different timelines associated with the development of drugs/biologics versus diagnostics, the general concurrent approval requirement outlined in the guidance could add significantly to the time required for commercialization of products, both drugs/biologics and diagnostics.”
Bradley M. Thompson, an attorney at Epstein Becker, said the final guidance is fine as far as it goes, but it is a general document and leaves a lot of open questions. In several areas, the guidance suggests meeting or consulting with FDA to figure out how to approach issues with co-development of drugs and companion diagnostics.
“That’s a good idea, and something innovators do currently, but it does not provide much insight into FDA’s thinking,” said Thompson. “The guidance also explains that FDA wants a companion diagnostic to be approved before the drug it is being paired with. But the agency goes on to say that depending on the facts, it might allow the drug to come to market before the companion diagnostic. This acknowledgement that FDA will be flexible is a good thing, but having more specific guidance on steps that innovators can take to avoid a lagging companion diagnostic approval would be more helpful.”
Thompson added that FDA has been developing a substantive guidance on co-development of drugs and diagnostics for a few years that should provide much more insight into the agency’s thinking, both from the drug side and diagnostic side of FDA.
“My understanding is that the co-development guidance was being held up based on concerns that it would impact FDA’s previous LDT enforcement discretion policy,” said Thompson. “But now that FDA has moved ahead with releasing its proposed framework for regulating LDTs, my hope is that the co-development guidance will follow soon. This co-development guidance could be a huge step in clarifying the standards for drug and diagnostic co-development, and move us from the more ad hoc approach to regulation that is in place today. Clearer standards could provide a boost to development of drug-diagnostic pairings that benefit patients. So the sooner the guidance comes the better.”