The FDA released another draft guidance intended to govern when a device maker submits a new regulatory filing for changes made to a 510(k) device, a document that drew substantial support from industry on several points. However, device makers are making the argument that the draft's discussion of changes to a device's intended use is inherently flawed, including the charge that the draft guidance has strayed into First Amendment issues.

The August 2016 draft guidance followed an unsuccessful attempt in 2011 to revise the so-called K97 guidance, a holdover from the 1990s, but the pushback on the 2011 version was sufficiently intense that Congress forced the agency to withdraw the document. This latest draft guidance offers several flowcharts to aid in clarity, but indicated that a deletion of a contraindication from a product label could trigger a need for a new regulatory submission. (See Medical Device Daily, Aug. 8, 2016.)

Mark Leahey, president and CEO of the Medical Device Manufacturers Association, said in a Nov. 7 letter to the docket that K97 "should be reviewed and updated," although Leahey said the concept of risk management "is applied inconsistently throughout."

On the point of labeling, Leahey asserted that the FDA is "overly broad in its regulatory interpretations," alleging that the agency is "attempting to address First Amendment/truthful and non-misleading issues" in the draft. He recommended the agency address such issues in a separate document, which may or may not be in the near offing despite a two-day FDA meeting on the subject. (See Medical Device Daily, Nov. 11, 2016.)

The draft guidance made use of the term "substantive change," but Leahey argued that this term has not been defined in regulatory terms and that the term as used "appears to encompass nearly all types of labeling changes," without due consideration of risk assessment. However, he stated further that the regulations deliberately separate the conditions that would trigger a need for a new filing for new intended uses from those that would trigger a new filing for changes to device design, materials and manufacturing processes.

Leahey stated also that the cumulative changes imposed on a device type over time "should be evaluated," adding that MDMA finds it plausible that a device maker should "review all changes for regulatory impact ... not only the last change." He said the draft is unclear on how much documentation would be required to spell out the impact of the iterations involved, making the case that a re-visitation of every change in each previous iteration "would be extremely burdensome without any corresponding benefit."

Also commenting on the draft was Ruey Dempsey of the Advanced Medical Technology Association, who also acknowledged a need to revise the K97 guidance. Dempsey said AdvaMed was "very pleased" that the agency made allowances for the use of the quality systems regulations (QSRs) in determining whether a new filing is needed, one of the arguments industry made in response to the 2011 draft guidance. On the other hand, Dempsey said the notion of risk management "is inconsistently applied throughout the document," and suggested the agency revisit the draft to determine where further clarification might be imparted.

Dempsey also took up the labeling/indications for use discussion, but was more explicit than MDMA's Leahey on this issue. Dempsey made the case that the FDA was "conflating two distinct regulatory concepts" by applying the regulatory standard of a significant impact on safety and effectiveness to a change in intended use.

Dempsey remarked that the administrative history pertaining to such matters "is not terribly revealing of the thinking behind" the regulations dealing with changes to design, materials or manufacturing, but she said the regulation nonetheless "makes clear that there are two tests" for establishing whether a new filing is necessary in reference to intended uses versus design/manufacturing/materials changes.

Pamela Forrest and Scott Danzis of the law firm of Covington told Medical Device Daily that one big difference between this new draft guidance and the previous versions is that the ambiguity is reduced substantially. Forrest said, "from our vantage point, this guidance is clearer than the 2011 draft, and more user friendly." She said she does not see significant content changes, but noted that this document serves to "clarify some points" that were not well characterized in K97.

Despite some of the concerns expressed by device makers, Forrest and Danzis said they were not persuaded of the notion that a device maker would have to routinely make an exhaustive effort to conduct a risk assessment farther back than one iteration on a device's predicate tree. However, Danzis remarked, "there may be some room for additional clarification" on that point.

Forrest said this new draft is much more clear about the role of risk assessment and routine verification and validation of changes to design, manufacturing, and materials, and Danzis remarked that even when a new 510(k) isn't necessary, "the net result is that there will be greater documentation associated with their letters-to-file" for many manufacturers.

More data of course means more communication with a contract manufacturer, but Danzis made the case that the additional clarity of the new draft does not relieve a device maker of documentation requirements, something that trips up many device makers up in FDA inspections.

"It's not enough to answer 'yes and no' to the flowcharts. You have to do a more substantive analysis" of any changes to ensure those changes comply with the regulations, Danzis said.