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Regulatory Focus™ > News Articles > 3 > Investigational IVDs: Companies Seek More Clarity in Draft Guidance

Investigational IVDs: Companies Seek More Clarity in Draft Guidance

Posted 29 March 2018 | By Zachary Brennan 

Investigational IVDs: Companies Seek More Clarity in Draft Guidance

Illumina, Merck and industry groups BIO and AdvaMedDx are seeking further explanations and examples from the US Food and Drug Administration (FDA) in guidance on investigational in vitro diagnostics (IVDs).

The 26-page draft guidance, released in December 2017, is intended to help sponsors and institutional review boards (IRBs) in making determinations about the risks of investigational IVDs used in therapeutic product studies.

In comments on the draft, BIO, for instance, said its members would benefit from more clarity on what would constitute a non-investigational device study and would thus fall outside the scope of investigational device exemption (IDE) requirements.

Some examples where “uncertainty remains,” BIO said, include:
  • “When the intended use of an approved IVD is unchanged with the exception of the associated therapeutic product (i.e. same assay, same target/indication, different drug), would the approved/cleared IVD be considered investigational?
  • Whether an IVD is investigational if the purpose of the study is not to generate safety and efficacy data in a clinical trial in order to obtain clearance or approval for the IVD (i.e. an early clinical trial prototype assay vs one that is intended to be commercialized).”
BIO also requested additional examples of known uses of IVDs in therapeutic product trials, such as, “those that are considered non-significant risk and exempt from IDE submission requirements. A suggestion is to include a more comprehensive list of known, potential, and/or most common uses of IVDs in therapeutic product trials and provide explanation as to why it is considered investigational vs. noninvestigational.”

Illumina echoed those sentiments, saying some of the descriptions in the draft “are terse and fail to recognize how difficult these risk determinations can be. We suggest that FDA, based on its regulatory review experience over the past 5 years, provide concrete examples that could help. These examples might be added as expanded text or included in an appendix.”

Merck, meanwhile, noted that in oncology trials, patients are already exposed to significant risk from their disease, so it’s asking FDA “to re-consider including biopsy procedures for the purposes of Significant Risk (SR) determinations. The biopsy procedure and its risks are included in the Informed Consent and the patient and physician make a conscious decision to have the procedure done after reviewing the potential benefits/risks.
Having this as part of the SR criteria introduces potential ambiguity for trial eligibility and may prevent otherwise eligible patients from participating if sponsors decide to exclude such biopsies from eligibility to avoid the SR determination and subsequent need to file an IDE.”

FDA’s requirement that a sponsor have an approved IDE to enable biopsy procedures “potentially delays trial start (and access to potentially beneficial treatment) until the assay is ready and performance data generated, when these activities could have been done in parallel to trial progress and prior to data analysis,” Merck added.

AdvaMedDx also said it supports the option of allowing sponsors to submit all IDE components to an IND rather than requiring both an IDE and an IND.

“We believe that the combined IDE/IND process particularly could be successful for products for which the FDA has a center of excellence scheme in place, e.g., oncology,” the group added.


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