PMA supplement guidelines at last, but industry might not be satisfied.
Device companies are happy to finally have guidance on paper, but whether the enthusiastic clapping will continue as industry members read the document and have a chance to comment remains to be seen.
One potential cause for concern: in the new draft, FDA primarily relies on general descriptions and multiple case examples rather than ostensibly more detailed and precise flow diagrams preferred by industry.
The draft, entitled "Modifications to Devices Subject to Premarket Approval (PMA)--The PMA Supplement DecisionMaking Guidance," attempts to clarify criteria for determining what application is required when changes are made to a PMA device, its labeling, its manufacturing process, or other variables.
It has been in the works at least since 2004 and replaces a 1998 draft guidance that FDA decided to abandon and remove from its Web site in 2005. Throughout this period, industry has expressed confusion and frustration about which of a range of potential supplements--from panel-track to 30-day notices--may be required in different situations.
"It is a complex area [and] it is important for companies to know ... what to expect--if it is going to be a 30-day notice or a 180-day supplement ... let alone a new original PMA," said Jeffrey Secunda, AdvaMed's associate vice president for technology and regulatory affairs, in a March 14 interview.
Further, he points out, the decision has specific financial implications because original PMAs and certain supplements have different user fees associated with them.
Thinh Nguyen, CDRH's PMA section director, has said that the supplement guidance is "probably the most important that will come out of the PMA program."
The 1998 draft guidance included multiple interconnected flow charts offering decision pathways for when to submit a supplement for five types of modifications: changes due to recalls and field corrective actions, labeling changes, technology or performance changes, packaging/sterilization changes, and materials changes. It did not, however, define specific supplement types and lay out criteria for when to proceed with each.
Industry was generally satisfied with the 1998 draft, but FDA was concerned that it was not clear enough and was causing disputes.
In 2004, when industry got word from FDA that the draft guidance needed to be reworked, AdvaMed formed a working group and by the end of the year submitted a proposed revision to the agency. It included modified charts, inserting the supplement types into the pathways, and making other adjustments.
FDA decided in the end to completely rework the guidance, however.
The agency "understands that there is a general desire among PMA holders for a detailed flow chart or easy to use paradigm," the March 9 draft states. "However, FDA does not believe the complexity and uniqueness of Class III devices makes it possible to establish that type of guidance."
The draft guidance includes a section for each possible submission that could be made as a result of a product modification, a general description of when it should be submitted, and four to ten examples of already approved supplements and why they were required. There is also one very general flow diagram broadly summarizing the document.
According to the draft, a new PMA is typically required "when a modification results in a device design so different from the original that the pre-clinical and clinical data you submitted on your original device are no longer applicable." A panel-track supplement will probably suffice when the indication for use is changed to require new clinical data but the design remains the same.
Meanwhile, a less stringent and more inexpensive 180-day supplement usually works when new pre-clinical, but not clinical tests, are required to assure safety and effectiveness following a modification. For instance, this supplement type was accepted when a company altered the battery and the LCD display for an electronic bone growth stimulator.
Other supplement types discussed in the guidance, which typically involve even more minor product adjustments, include real-time supplements, "special" PMA supplements (changes being effected), a 30-day notice/135-day supplement, and a manufacturing facility site change supplement.
"I think industry is disappointed" about the new approach to the guidance, Secunda indicated, although he conceded that he had only briefly reviewed the draft before the interview.
Secunda also noted that it was "unfortunate" that the PMA annual report draft guidance, issued last October, was released before the supplement guidance. "This document for the PMA supplement decision-making process should have been the comprehensive document to guide industry," and in that case, "the annual report guidance would simply be a technical document as to how to fill it out," he explained.
As it is, AdvaMed is charging FDA with going beyond its legal authority in its request for information in the annual report draft.
AdvaMed will collect feedback from its members on the supplement draft and submit formal comments to the agency before the June 9 deadline.
For the time being, industry representatives tell The Gray Sheet that they are just happy to finally see draft guidance issued.