Significant Changes Seen in NGS Guidance: Attorney

Attorney Allyson Mullen (Hyman, Phelps & McNamara) says FDA made significant changes in the finalized 4/13 next generation sequencing guidance (NGS) without any explanation for why its thinking on the subject has changed. Writing in her firm’s FDA Law Blog, Mullen says the substantive changes in the guidance distinguish it from a companion guidance on use of public health genetic variant databases that has no substantive changes.

“It is important to note that FDA provided no explanation for the changes to the NGS guidance,” she says. “Unlike the case with regulations, where FDA describes the reasons for revisions, guidances keep readers guessing as to why FDA’s thinking has shifted.”

One of the major changes to the NGS guidance’s scope, according to Mullen, is that it now applies only to NGS-based in vitro diagnostics (IVDs) intended to diagnose suspected germline diseases in symptomatic patients. She writes that the original guidance did not limit the scope to only symptomatic individuals. “This is an important change that will limit the scope and impact of the guidance to industry,” Mullen writes.

The post reports that the guidance contains several helpful new sections, including one regarding recommendations for reviewing changes to device design and production. That section pertains to all changes, including those that may or may not require premarket review. There is also general guidance in the document about assessing changes, including revalidation. And there is a new appendix with illustrative examples to aid in the document’s recommendations about analytical tests.

Mullen says the finalized guidance includes a notably shorter discussion of the possible exemption of NGS-based tests for germline diseases as compared to the draft. She says the draft had a full section on the possibility of an exemption for such tests. “The final NGS guidance still leaves open the potential for NGC-based tests being exempt from premarket notification,” she concludes. “But, with a much more limited discussion in the final guidance it may be a signal that the agency believes it is less likely that these tests will actually be exempt once classified. The guidance continues to state that it anticipates that the de novo pathway is the appropriate premarket pathway for these IVDs.”