The final rule will have the biggest impact on the “large, established players that have big quality systems that could take a year or more to overhaul,” Brad Thompson, a lawyer representing combination product companies with Eckstein, Becker and Green, told In-Pharmatechnolgist.com.
One of the main issues is that quality system requirements for the device part of a combo product will need to apply to drug quality systems and vice versa, Thompson said.
For device quality systems, “design controls basically say that when you make a new device – first you figure out what to accomplish, then design the process to meet initial criteria and then test the product” in order to show a linear, logical progression, Thompson said. But when manufacturing a combo product and design controls have to apply to both the drug and device, “I can assure you the drug wasn’t designed under these design controls," he added. And how companies will prove this crossover in their quality systems is “anything but clear.”
In its final rule, the FDA said it will release further guidance on how to comply with it but did not provide a timeline.
A lot of companies are moving in the direction of somewhere between tweaking and overhauling their quality systems, Thompson said, but the rule takes effect in six months, which will likely be before the new guidance is released and could put companies in limbo on when to begin investing in the new quality systems.
Thompson also noted that a lot of devices include a number of different parts from supplier companies that might not even be in the medical industry, but now may have to comply with these new requirements. The FDA initially exempted suppliers but now it is unclear if suppliers, even if they provide all of the components of a product but do not manufacture the actual device, will need to comply, Thompson said.
Another problem is that for years the FDA has been relatively silent "around the tactical questions companies have on putting together a quality system for combo products,” and now that the rule is out but guidance is in development, Thompson said it will be aggravating if the agency says it cannot discuss the rule because of the forthcoming guidance.
The issue of quality systems is becoming a more central theme at the FDA. In fact, the FDA may even adopt a grading system whereby manufacturers would be assessed on their quality performance in a system similar to restaurant grades or HMO scorecards, according to a recently published commentary in Nature by Janet Woodcock, director for the Center for Drug Evaluation and Research (CDER), and Marta Wosinska, director of the economics staff at CDER.
“The heart of the quality problem is the fact that generic manufacturers compete on price” and buyers often “consider any given generic products as perfect substitutes, giving manufacturers little room for differentiation. Therefore, buyers have not been attuned to differences in the quality of production,” the authors write.
They give the example of shortages of generic sterile injectables, in which defects “can be difficult to detect because microbial contamination may be non-uniform and episodic.” And low margins in the products make investments in quality systems and other manufacturing upgrades difficult.
But because of recent shortages, the FDA has to take action “to engage the marketplace to help address the manufacturing problems, which unilateral FDA actions have not been able to prevent,” they write.