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Manufacturing Presents Complications for Drug-Eluting Stents


Posted by mddiadmin on October 1, 2004

Originally Published MDDI October 2004

NEWSTRENDS

Manufacturing Presents Complications for Drug-Eluting Stents

The Cypher stent from Johnson & Johnson's Cordis gained only minimal market share with Boston Scientific's recall.

Erik Swain

Despite all the negative publicity from Boston Scientific Corp.'s (Natick, MA) massive recall of its Taxus drug-eluting stent, the product has not lost as much market share as some expected. This may be because its main competitor, the Cypher stent from Johnson & Johnson's Cordis Corp. (J&J; Miami), has had manufacturing issues of its own.

Boston Scientific issued three recall notices in July and August 2004 because of manufacturing problems that caused the catheter systems' balloons to fail to deflate after stent deployment on rare occasions. In all, almost 100,000 Taxus and bare-metal stent systems were recalled despite the problem affecting only one in 12,000 to 15,000 stents. At press time, FDA was in the process of inspecting Boston

Scientific's plant in Galway, Ireland. Those results could bring further consequences. Yet, by the end of August, Boston Scientific had regained about 85% of Taxus' sales volume, according to the company.

“We think we've gained it back as quickly as we have for two reasons,” says Eric Simso, Boston Scientific's vice president of stent marketing. “One, we were able to keep up the supply. Two, we think we did a good job communicating with our customers. We announced [the largest of the recalls] on a Friday, had our reps out to the cath labs on weekends, and by the end of the day on Monday, we had 75% of the products back in our hands or otherwise under control. By the end of the first week, we had taken back virtually all of the affected products and resupplied [the customers]. The physical management of it gave people confidence that we knew what we were doing.”

In most cases, the resupply was immediate. Certain sizes had back orders, but those were resolved within a day or two, Simso says. “We definitely lost market share, but we were in a position where it did not have as great an impact as it could have. It helped that Boston Scientific and our reps have good relationships with our customers. That meant they tended to give us the benefit of the doubt.”

The next task, he says, is to reassure the customers who no longer want to use Taxus or who want to take some time to evaluate the company's response to the problem before using it again. “On an individual basis, we are going to each [customer] to try to understand the issues they have,” he said. “Then we will do something about it. Some of them are saying that they won't use Taxus until we show them 1–3 months of real-life history that the problem has been solved. They want us to give them a comprehensive analysis.”

Some customers, however, “gave J&J an opportunity to come in and give them a better economic deal,” Simso says. “So J&J got some new contracts, and we may have to wait until the end of the year to get back in and convince those customers to refresh our programs.” Other customers, he notes, used the recall as leverage to negotiate a better price for Taxus, which he says is perfectly reasonable under the circumstances.

Another factor in Boston Scientific's regain of market share, however, is that J&J has had manufacturing and supply issues of its own. An April 2004 FDA warning letter cited “serious underlying problems in … manufacturing and quality systems” at six Cordis plants that manufacture Cypher. It cited, among other things, problems with corrective and preventive action programs, insufficient investigation of out-of-specification test results, and inadequate validation of the stent-coating process. Industry observers say that the most significant problem that remains is adequately explaining failures of drug-elution tests, which gauge whether the correct amount of drug has been eluted over a certain period of time.

Those issues, plus a structure that has the manufacturing, coating, packaging, and sterilization processes all performed at different facilities, have rendered J&J unable to supply its product as quickly or as extensively as it would like.

The Taxus Express Paclitaxel-eluting coronary stent: Boston Scientific has focused on reassuring customers.

J&J declined to comment for this article other than a brief statement by Cordis spokeswoman Terri Mueller. “With regards to supply, we are
continuing to ramp up production of the Cypher stent, given the recent market events and physician preference for the product,” she says. “The manufacturing of a drug-eluting stent is a complex process. We are committed to providing our customers with safe products that make a positive impact on patient treatment.”

While both companies' problems might reflect the difficulty of manufacturing a complex combination product, no one is citing them as indicators that FDA approved the products too quickly.

“I think there will be some times where we see things come up simply by the size and nature of the postmarket experience, as opposed to the premarket experience,” CDRH director Daniel Schultz told MD&DI. “That is, there might be events that may be quite serious but, because they occur at such a low rate, are difficult to pick up in the premarket evaluation.” (More of the interview with Schultz can be read on page 70.)
Simso agrees. “Our problems and J&J's are in completely different categories,” he said. “Ours was related to the catheter system and also occurred on bare-metal stents. But these are products that are tough to design and make work. There have been a lot of failures out there. There are issues in this category that device companies are not used to dealing with. There are analytical tests that we've never done.”

Patrick Driscoll, president of MedMarket Diligence (Foothill Ranch, CA), notes that “in markets with that kind of potential, even a slight misstep can get blown out of proportion. The stakes are so high that it heightens sensitivity. Adding to the complexity is that devices have readily measurable performance characteristics, while drugs are a much different beast.”

Copyright ©2004 Medical Device & Diagnostic Industry


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