Full article reprinted from "The Gray Sheet" - October 20, 2008
FDA previewed several changes it will make in its final drug-eluting stent guidance at the Transcatheter Cardiovascular Therapeutics symposium in Washington, D.C., on Oct. 15.
Full article reprinted from "The Gray Sheet" - October 20, 2008
FDA Previews Final Drug-Eluting Stent Guidance
FDA previewed several changes it will make in its final drug-eluting stent guidance at the Transcatheter Cardiovascular Therapeutics symposium in Washington, D.C., on Oct. 15.
Having reviewed comments on its March draft guidance, plus input from an April FDA-industry workshop, the agency expects to issue a final guidance in early 2009 (1"The Gray Sheet" May 12, 2008, p. 7).
"Our best guess is that we will have the modified document posted in about four to six months," Elizabeth Hillebrenner, a biomedical engineer in FDA's division of cardiovascular devices, said.
Most of the changes will be in the "engineering evaluation" section of the guidance, Hillebrenner said. FDA is also tweaking the animal and clinical studies sections.
The document will add a table outlining the engineering tests required for drug-eluting stents, beyond those required for bare-metal stents. These include coating integrity tests and particulate matter tests in three settings: baseline, simulated deployment and chronic use.
Coating integrity tests involve visual assessment of the stent, usually done by scanning electron microscopy.
For the baseline test, the stent is expanded to its nominal diameter in the air. For simulated deployment, the stent is tracked through a tortuous path and deployed to its maximum labeled diameter in a mock vessel. Chronic use tests track multiple stents through a tortuous path, maximum deployment in an overlapped configuration in a bent mock vessel, and a simulation of one- and 10-year fatigue cycles.
Particulate matter testing looks at potential risks from downstream particles of coating and requires similar assessments.
The chronic use tests for coating integrity and particulate matter may be combined as long as they do not interfere with each other, Hillebrenner noted.
The guidance will also explain how the simulated deployment particulate matter testing will inform stability specifications.
FDA made no additional recommendations for degradable stents or coatings, but stresses that if a sponsor has a degradable stent or a degradable component, the company should "please come talk to us right away," Hillebrenner said.
"The first thing we're going to ask you is, 'What is the degradation profile of your biodegradable component?'"
PMA Submissions Will Need 18-Month Data
The only real edit in the clinical trials section is the pre-market requirement to follow at least 50% of patients out to 18 months. The draft guidance had called for 24-month data on a substantial number of the patients (2"The Gray Sheet" March 31, 2008, p. 8).
Given the rates of trial enrollment so far, the extra six months of follow-up beyond a 12-month primary endpoint will not be burdensome, FDA and industry agreed.
"We want to have data on some patients longer-term to see what happens after discontinuation of thienopyridine [dual antiplatelet therapy] use," Hillebrenner explained.
In addition, companies with stents longer than 30 mm will no longer need to complete a separate animal study on their longest stent model, according to FDA.
Guidance Shortens Preclinical Timeframes
While the final guidance is pending, the additional clarity provided by the March draft guidance has helped shorten preclinical timeframes, according to Campbell Rogers, Johnson & Johnson/Cordis' chief technology officer.
"The actual benefits of having a roadmap from the development side cannot be overstated," Rogers said at the TCT meeting.
The draft guidance was at least three years in the making. However, FDA says updating the guidelines in the future should be much easier.
- Jessica Bylander
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