Bioresorbable antibiotic-eluting surgical mesh helps prevent the colonization of bacteria at wound sites.
In order to properly evaluate these products, FDA established a group to deal solely with items that extend beyond each relevant FDA center’s narrow realm. The Office of Combination Products (OCP) evaluates a combination product’s primary mode of action (PMOA). The PMOA is determined by assessing whether the item’s main function is attributable to its device, drug, or biologic component. Upon doing so, the OCP designates the product to the corresponding regulatory center.
“Drugs, devices, and biologics are differently regulated. And while there are a lot of similarities, there are also some differences,” says Mark Kramer, director of the OCP. “The overriding challenge is how to bridge the differences in such a way that is appropriate for combination products without being burdensome [to industry].”
During its first full year of operation in 2004, the group reported that 251 combination products were filed– a testament to their presence. The proliferation of combination products is apparent in the 275 submitted to FDA in 2005, according to Kramer.
One of the most recently approved products, Exubera, is the first noninjectable insulin for the treatment of Type 1 and Type 2 diabetes. The product comprises a drug and an inhalation device that expedites insulin delivery to the bloodstream for diabetes treatment.
The high incidence of diabetes coupled with the reliance of many sufferers on insulin pumps or regular injections has created a welcoming market for Exubera. The promise of a pain-free and convenient diabetes treatment is appealing to many diabetics.
The combination product Exubera enables people with Type 1 and Type 2 diabetes an alternative to painful needles through its inhalable form of insulin.
Exubera resulted from a complex collaboration of companies. Pfizer Inc. (New York City; www.pfizer.com) and Nektar Therapeutics (San Carlos, CA; www.nektar.com) spearheaded the project. Bespak plc (Milton Keynes, UK; www.bespak.com) and the Tech Group, a div. of West Pharmaceuticals (Scottsdale, AZ; www.techgroup.com), shared responsibility for the mass production and commercialization of the inhaler.
Because of the combination aspect of the product, the manufacturing process was more complex than with a traditional device, according to Mike Treadaway, Tech Group general manager of drug-delivery devices.
“This is a combination product,” Treadaway says. “From the standpoint of quality systems and compliance, the field narrows down. We were one of just a handful of companies that had a demonstrated capability of commercializing a combination device such as this.”
The cross-disciplinary approach required to make a product such as Exubera demands more attention to detail. Treadaway notes, “The biggest challenge is making sure that, because this is a combination device, the quality systems are in place and compliant with regulatory requirements.”
Exubera is slated for release in mid 2006. While Exubera may currently own the spotlight, drug-eluting stents have been the newsmakers earning combination products a home in the headlines.
The market for drug-device combinations worldwide was valued at $5.4 billion in 2004 and is expected to rise to $11.5 billion in 2010, according to a report published by Business Communications Company, Inc. Of that projected $11.5 billion, $8 billion will stem from drug-eluting stents, the report states.
After only a few years on the market, the drug-eluting stent has garnered many accolades. Hartford Hospital in Hartford, CT, goes so far as to champion it as the “biggest breakthrough for interventional cardiology in 25 years.”
While drug-eluting stents prevent restenosis, other combination products are targeted at thwarting infection. Many combination products surfacing are made up of a device equipped with an antimicrobial coating.
This rash of antimicrobial-coated combination products is in response to alarming statistics regarding hospital-acquired infections (HAIs). According to the Centers for Disease Control and Prevention (CDC), HAIs account for an estimated 2 million infections and 90,000 deaths each year. In an effort to decrease these dramatic numbers, many device manufacturers are releasing their products with protective coatings to help stave off infection-causing bacteria.
The urinary tract is the most frequent site of HAIs, with an estimated 66–86% of these infections resulting primarily from urinary catheterization, according to the CDC. This rampant problem has been addressed in recent years by the use of antimicrobial catheters.
Touting its dedication to the development of new combination products, TyRx Pharma Inc. (Monmouth Junction, NJ; www.tyrxpharma.com) has announced it has applied to FDA for an antimicrobial surgical mesh. This combination product is characterized by its bioresorbable polymer antibiotic-eluting capability.
Protecting against biofilm formation of common surgical site infection (SSI)–causing bacteria, the surgical mesh is effective for 5–7 days following implantation. The mesh is suited for use in hernia repair and similar abdominal problems that need reinforcing material. The company has also developed an anesthetic-coated surgical mesh.
The development of such a product demands a different mindset than conventional medical devices, according to William Edelman, CEO of TyRx. “The combination product space requires a unique perspective on both medical devices and pharmaceuticals,” he says. “The development team cannot be biased with one particular industry perspective. Success in this space can allow highly efficient use of capital during the development process, shorter time to market than for pharmaceuticals, and a less onerous path through the FDA approval process.”
As the market for combination products expands, plenty of companies will no doubt be clamoring to meet the demand. The dire need to reduce nosocomial infections in hospitals, in addition to the potential patient benefits they propose, will open the floodgates for the rush of combination products expected to flourish in the coming years.
Yet despite their countless benefits, developing effective combination products may be challenging. Research conducted by Georgia Tech and Emory University reveals that the body may react negatively to such products. According to the research, the body may perceive a biomedical implant as a threat, leading to its failure. Other reactions can occur with biomaterials. The research concludes that the reactions may affect one another when triggered simultaneously, as could be the case with combination products.
While there is still much to explore in terms of combination products, one thing can be certain. Combination products are altering the medical community from production to regulation to treatment. In some cases, maybe two products are better than one.