HOSPITAL PRACTICE

Do combination products spark turf wars?

Is it a drug or a device? Consider the drug-eluting stent being developed by Johnson & Johnson's subsidiary Cordis Corp. Is it a stent with a pharmaceutical kicker, or a drug piggybacking on a stent for more precise delivery? The question has already crept into hospital pharmacies and ambulatory care clinics.

Consider these other products:

• Intravenous sets and catheters are routinely coated with heparin and other drugs.

• Refillable pumps, both freestanding and implantable, are widely used for long-term pain relief.

• Wafers impregnated with carmustine (BICNU, Bristol-Myers Squibb) are surgically implanted to deliver precise low-dose chemotherapy after excision of a brain tumor. Yet while carmustine is traditionally administered as an IV drug and handled by pharmacy, the wafers are ordered by and billed through the OR, said Dominic Solimando, president of Oncology Pharmacy Services Inc. and a pharmacist at Walter Reed Army Medical Center. "Pharmacy doesn't touch them."

Pharmacists tell Drug Topics that combination products generate few arguments between departments. Most items that might spark a dispute, such as drug-coated IV sets, are clearly either device or drug.

In the case of refillable pumps, responsibility is often divided. At Walter Reed, pharmacy is responsible for the drug, refilling pumps as needed, Solimando said. The clinic is responsible for the pump, tubing, and other supplies. At other clinics, he added, medicine is responsible for both pump and drug. Others put pump, drug, and supplies under pharmacy.

"It's not a big turf battle," he explained. "It's more a matter of who has money in their budget. Most pharmacies don't see catheters and IV sets as their area. They're part of hospital supply. An IV set is an IV set, even if it's coated with a drug."

The Food & Drug Administration uses that logic in initially approving a product. "FDA assigns it to device review or drug review based on the primary mode of action," explained Gary Stein, director of federal regulatory affairs for ASHP.

But the lines between drug and device can be fuzzy. Pfizer and at least four other pharmaceutical firms are developing inhalable insulin. They are creating novel forms of insulin and novel types of inhalers to deliver it.

So what's more important, the novel drug formulation, the novel delivery system, or the drug-device combination? While it's not an issue now, said Melsen Kwong, manager of pharmacy services at Cedars Sinai Medical Center in Los Angeles, "I can see it becoming one as the lines between drugs and devices blur. I'm not sure how we're going to deal with it."

For now, choosing between drug and device is relatively simple. The drug-eluting stent, for example, was classified as a device. So noted Mark Kramer, director, Combination Products Program in the FDA's Office of the Ombudsman. "The overall intent and the principal mode of action are to keep the artery open," he explained. The drug, sirolimus (Rapamune, Wyeth), plays a secondary safety role by significantly reducing the accumulation of plaque at the stent site, which reduces the need for restentosis. Approval of the stent—already sold in Europe under the brand name Cypher—is being handled by FDA's Center for Devices & Radiological Health. The review is being assisted by the Center for Drug Evaluation & Research, which is responsible for approving new drug products.

The FDA's Combination Products Program handles drug-device, drug-biologic, and biologic-device combinations. If a new product appears to cross category lines, the maker submits a Request for Designation of where the product should be approved. The agency then makes its own decision. "Combination products are only a small fraction of total submissions," Kramer said. "But some of the most complex products we get are combinations. That's likely to continue as manufacturers look to technology to increase safety and efficacy. "

The approval category can affect how a new product is sold. New drugs and biologics are handled by drug sales reps; devices are handled by device salespeople. Many hospitals and outpatient clinics have restricted access by drug sales reps, noted Andrew Burns, spokesman for device maker Smith & Nephew. But device sales reps have almost unlimited access to their physician customers.

Smith & Nephew is bringing the first drug-coated orthopedic sleeve, OrthoGuard, to market in October. The polyurethane tube covers orthopedic wires and screws where they penetrate the skin, releasing low doses of gentamicin to inhibit infection. "Our salespeople spend 80%, 90% of their time with physicians in their offices and in the OR during surgeries," Burns explained. "Approval as a device is crucial to physician access and to our sales effort."

Fred Gebhart

Fred Gebhart. Do combination products spark turf wars?.

Drug Topics

2002;19:42.