Dr Steven Richter, Microtest president and chief scientific officer, has addressed the issues associated with the US Food and Drug Administration's (FDA) regulatory process for "combo products" in a paper Combination Products: Navigating Two FDA Quality Systems. "For manufacturers, along with these exciting new opportunities, the convergence of drugs/biologics and devices also brings a host of regulatory challenges. One - underway now in the regulatory departments of both pharmaceutical and medical device manufacturers - focuses on their struggle to address a host of testing guidelines, practices, and regulations unique to the development and production of combination products," Richter said. According to reports, the combo product market was estimated to be worth $5.9bn in 2004 and is expected to increase to $9.5bn in 2009. Currently, an estimated 30 per cent of new products under development are combo products, but as yet the FDA has not issued guidelines specific to these. "There is a growing realisation among both groups [pharma and device manufacturers] of the therapeutic benefits of putting a drug into a medical device and providing it as a combination unit and using the resulting product to deliver drugs directly to certain areas of the body," Richter said. Approval of combo products is determined by the FDA's Office of Combination Products, which determines the primary mode of action for the product - whether the device is for drug delivery, has physical medical properties, or incorporates a drug delivery system - and which FDA centre should be involved with the approval. "The combination product regulatory framework requires a unique perspective on both medical devices and pharmaceuticals/biologics. The dichotomy between drug GMP's, biologics product standards and medical device QSR's is immutable. A combination product manufacturer must have a robust pharmaceutical GMP system in place that addresses some of the issues with the device QSR's," Richter said. According to the Process Analytical Technology approach taken on by FDA centres, drug regulations are moving away from products to processes, with an increased emphasis on quality by design and design of experiments strategies. "Quality by design is an important tool to identify the correct information needed to demonstrate robustness and process control. These analytical technologies will be the driving forces for validating critical process controls used in the manufacture of drug/biologic products." Richter said the largest problem facing combo product manufacturers would be the scale-up process because of quality control measures. Sterilisation of combo products could also be a problem due to the incompatibility between the drug product and the sterilant, Richter said. He said he expected FDA guidelines to include Process Analytical Technology and design of experiments requirements. "When it comes to developing robust analytic systems for combination products, the device manufacturer's knowledge base will be challenged in their ability to manage a regulated drug product and follow CMC controls."