Illumina, Genentech and BIO Weigh in on FDA Draft Guidance on Companion Diagnostics

Regulatory NewsRegulatory News | 18 October 2016 |  By 

The six public comments on the US Food and Drug Administration’s (FDA) draft guidance on companion diagnostics were mostly positive, with Genentech calling the draft “crucial for the advancement of personalized medicine,” while Illumina said it was “worth the wait,” though all commenters expressed interest in more clarity from FDA.


The long-awaited draft guidance, released in July, was in the works for more than a decade and is meant to be a practical guide to assist drug and in vitro diagnostic (IVD) sponsors developing these two products simultaneously.

But rather than offering proscriptive guidance, FDA sought a more open-ended approach, noting, “various approaches may be acceptable to obtain the data needed to support contemporaneous marketing authorization of a therapeutic and an accompanying IVD companion diagnostic, so “FDA strongly recommends that the sponsors of both the therapeutic product and the IVD meet with the appropriate FDA review centers prior to launching a trial intended to advance the development of the therapeutic product and the IVD companion diagnostic.”

The concept outlined in the guidance is not new, however, as in 2014, more than 20% of new drugs and biologics were approved alongside such a diagnostic test, and 2015 saw that portion rise even more, with 28% of new drugs and biologics approved alongside a diagnostic.

Amy Miller, PhD, executive vice president of the Personalized Medicine Coalition, previously told Focus that she expects that moving forward, about one-quarter of all new drug approvals will include the approval of an IVD companion diagnostic.


Gene sequencing powerhouse Illumina makes clear that the draft “has been a long time coming, eagerly anticipated, but worth the wait.” The company also seeks more clarity from FDA on risk assessments and expectations for analytical validation prior to investigational IVD use in trials, as well as more detailed questions.

“There is an opportunity here for FDA to add clarity on this important decision making process. We suggest this discussion on significant risk versus nonsignificant risk determinations be expanded and put into an appendix with examples. This is a unique opportunity for FDA to help sponsors get this process right,” Illumina says.

In addition, regarding the section of the draft briefly addressing the analytical studies that should be conducted prior to a therapeutic product trial, Illumina noted the studies are not outlined in the section but listed in a footnote.

“We believe these terms deserve more than a footnote and that a more detailed description of FDA expectations is warranted. We suggest emphasis be placed on determination of limits of detection and cross reactivity instead of analytical sensitivity and analytical specificity,” Illumina says. “Additionally, we believe reproducibility is not always needed as part of the work done for these analytical studies. If the data from the within-lab precision studies where different operators and instruments are evaluated is solid and there is no reason for the manufacturer to suspect that site-to-site variability would be an issue, then we suggest reproducibility be evaluated as part of site studies during data collection in the actual therapeutic product trial.”


Janet Jenkins-Showalter, head of US regulatory policy at Genentech, meanwhile, offered similarly positive comments on the draft, though she also noted that for two previous draft guidance documents on next generation sequencing (NGS), “neither of them contain needed information regarding the Agency’s regulatory/evidentiary requirements for the co-development of a therapeutic in conjunction with high throughput diagnostics.”

Likewise, Genentech says that the scope of this IVD and drug co-development draft guidance “is limited, and therefore it does not address the requirements for development of complementary diagnostics or the challenges of co-development using high-throughput technologies such as Next-Generation Sequencing (NGS) based test panels, which are an increasingly attractive tool for both developers and providers.”

In addition, Genentech calls out FDA’s note about the relevance of this guidance for IVDs that might not be companion diagnostics, and says that “as both prognostic and predictive diagnostic tests proliferate, it would be helpful if the Agency could clearly delineate the types and categories of IVDs to which this guidance is applicable.”


The Biotechnology Innovation Organization (BIO), which said it’s supportive of FDA’s efforts, also calls on FDA to delineate the principles and criteria for making an assessment on companion vs. complementary diagnostics, particularly as FDA recently approved a device under this new category of complementary diagnostic.

BIO also calls for more clarity on other companion diagnostics that are not IVDs (ie. medical mobile application, wearables, etc.).

“Either by footnote, as noted for future IDE guidance or in the guidance text, BIO believes that it would be beneficial for FDA to provide recommendations on similarities and differences between IVDs and other types of medical devices,” the comment says.

“Similarly, it would be very helpful if the final guidance addressed some of the more challenging aspects of co-development such as multi-variate analyte CDx development, development and review considerations for ‘test system’ IVDs (i.e. comprised of assay, instrument, software). For example, the document could provide, among other considerations, more in-depth validation information for multi-variate companion diagnostics and/or provide reference to other guidance documents (i.e. Next Generation Sequencing-Based In Vitro Diagnostics draft guidance) and its relevance and application in the context of these important and novel technologies,” BIO says.

AstraZeneca and Others

AstraZeneca, meanwhile, made seven general comments and other more specific ones, including ones that seek more clarity on guidance on complementary diagnostics and clarifying between “patient enrichment” and “patient selection” and the resulting considerations on determination of significant risk uses of investigational devices.

The American Association for Cancer Research and the Diaceutics Group also commented on the draft.

Comments on FDA Draft Guidance on the Principles for Codevelopment of an In Vitro Companion Diagnostic Device with a Therapeutic Product


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