FDA, AdvaMed Seeking Clarity on Med Device Pre-Market Approvals

The FDA and the Advanced Medical Technology Association (AdvaMed) gave cardiovascular device manufacturers plenty to think about over the holiday weekend with information presented at an Aug. 28 workshop. The two bodies came together to explain requirements for 30-day notices and annual change reports for Pre-Market Approvals (PMAs), an important gateway to medical device access and commercialization.

The six and a half hour meeting tackled a wide range of topics, from the role of risk assessment to supplier changes as agency officials attempted to shed more light on when companies need to submit 30-day notices for manufacturing changes. Those changes that qualify for a 30-day notice submission affect device safety and effectiveness and either the manufacturing procedure or the method of manufacture. But device manufacturers must beware; a 30-day notice containing inadequate information could face conversion to a 75-day Humanitarian Device Exception (HDE) supplement or a 135-day PMA supplement. In these instances, the company will need to offer additional information or take further actions in order for the FDA to accept the change.

FDA announced the workshop in the Federal Register on Aug. 13, took many months to prepare and came more than a year after the FDA issued guidance explaining what changes qualify for 30-day notices and which ones do not. This meeting also came as the agency prepares to move 30-day notice reviews from the Office of Compliance to the Office of Device Evaluation (ODE), with the cardiovascular devices division piloting the program.

As Lindsay Pack of the Center for Devices and Radiological Health noted during the workshop, nothing will change in terms of the 30-day notice content. However, companies should keep in mind that the same reviewers who went over its original PMA will now evaluate the 30-day notices. Explaining risks will be critical; test set-ups and acceptance criteria may be challenged.

Pack also emphasized the need for clear, concise writing to ensure reviewers know what’s being changed right away. Exclude extraneous facts that won’t help the reviewer.

The FDA hopes the implementation of this “total product life-cycle approach,” for 30-day notices will run smoothly, as Christy Foreman, director of ODE, told workshop attendees. But both a lack of understanding and inadequate data-sharing seem to have caused frustration on all sides. During the meeting, FDA staffers emphasized the need for companies to use risk analysis in justifying their submissions in either 30-day notice or an annual report. ODE’s Erin Keith noted that although she had not worked with the cardiac industry during her time at the Office of Compliance, other device segments’ grasp of the use of risk analysis to justify their manufacturing changes was “pretty non-existent.” Echoing her frustration was Pack, who said companies often didn’t include an explanation of the risks driving the testing of changes. “I almost never see that laid out,” she said.

However, some companies may think that sharing too much data could get them “penalized,” a fear Pack tried to assuage.

Still, cardiovascular device makers seem to be gaining a firm grasp of what should be included in a 30-day notice, as Bill MacFarland of CDRH’s Office of Compliance noted. He recently looked over the numbers and saw, on average, that cardiovascular 30-day notices were converted to 135-day supplements 14% to 25% of the time. This year, however, that number has tightened to 8% to 11%, figures that he attributes to program maturation and increasing experience of reviewers. On the flip side, industry executives are increasingly putting themselves in the shoes of reviewers. For example, they are including narrative, pictures or drawing to illustrate the manufacturing changes to make things more meaningful for reviewers.

According to the FDA data through April 2012, the agency has determined that a few submissions did not qualify as 30-day notices. While this number has generally been four or fewer for each month, March saw 10. Still, quite a few are completed in 30 days or less each month. A total of 691 were completed between October 2011 and April of this year, according to FDA data.

Other meeting presenters highlighted an area in which device manufacturers seem to get hung up on whether to submit changes in an annual report or 30-day notice: equipment and software changes. As AdvaMed’s Melanie Raska noted during her presentation, a number of companies have seen their equipment changes converted from annual reportable to 30-day notices - something one of the association’s working groups noted. It formed a subgroup to examine the situation and how to resolve it. She shared several points manufacturers should consider when trying determine if a 30-day notice is needed:

1) Does the software directly affect the manufacturing process?

2) Does the change impact a process control?

3) Does the change impact accept/reject activities?

4) Are you changing the specifications or process parameters?

Interested parties have until Sept. 26 to submit comments pertaining to the issues discussed at the meeting.

Elizabeth Hollis is a former editor-at-large in the life sciences group at FierceMarkets, covering the medical device sector, among other areas.