Congress should establish a strong national strategy for the advancement of biomedical innovation, she said. But legislation should focus on what she called “real barriers to progress,” not “perceived problems.”
The Pharmaceutical Research and Manufacturers of America and the Advanced Medical Technology Association support the bill. JC Scott, AdvaMed's senior executive vice president of government affairs, said some of the bill's provisions would make FDA review of medical devices more efficient, reducing the cost of bringing a product to market.
A 2010 industry study estimated it costs companies about $24 million in FDA-related activities to bring a low- to moderate-risk medical device from concept to market and about $75 million for a higher-risk device. “We often talk about improving the regulatory review process, but it's not always about making it faster,” Scott said. “It's also about making it more efficient and predictable for companies.”
Debate over the bill comes as elected officials face pressure from desperate patients and their families to make new medical products more immediately available on a compassionate-use basis. Nearly a dozen states have passed “right to try” laws that allow terminally ill patients to seek an experimental drug without going through the FDA's compassionate-use process. The rationale is that the FDA's program is too slow to make potentially lifesaving drugs accessible. Critics, however, say such laws have no practical impact because manufacturers are not required to make their products available. They fear that doing so could undermine their clinical-testing process.
In January, Rep. Fred Upton (R-Mich.), chairman of the House Energy and Commerce Committee, released a draft of the proposed 21st Century Cures bill. It initially had bipartisan support, but House Democrats turned against it, saying the bill could potentially put the public at risk. Rep. Frank Pallone Jr. (D-N.J.) said the bill in its current form “could create more problems for our healthcare system than it solves.”
A key provision would change the FDA's current “breakthrough therapy designation,” a program that began as part of the 2012 FDA Safety and Innovation Act. That law allows the agency to identify and speed up the review of drugs whose early clinical evidence shows they may be better than current treatments for serious or life-threatening conditions.
Under the 21st Century Cures Act, the FDA could grant market approval to a drug with breakthrough designation based on its early stage testing for safety and effectiveness. After starting to market the drug, the drug's manufacturer would be required to conduct trials to demonstrate safety and effectiveness. Medical-device makers also would be able to apply for breakthrough designation for products that treat conditions where no alternatives exist, or that significantly improve on currently approved therapies.
In addition, the bill would require the FDA to create a new regulatory pathway for antibacterial medications that would allow for faster approval of such drugs by limiting their initial use to specific populations with severe conditions for whom current therapies have been ineffective. Other provisions would put new requirements on the FDA to shorten the length of time it traditionally takes to approve a new drug or medical device.
Though experts say those provisions would accelerate the review of new drugs, critics say they would limit clinical testing of new therapies before they entered the market which would increase safety risks to the public.
“The more you speed the process up at the beginning stages—Phase 1 and 2—the more I think you have to toughen up at Phase 4 when things are out in the world and you're trying to see what's going on,” said Arthur Caplan, a bioethicist at NYU Langone Medical Center. Under the FDA's current clinical trial process, products in Phase 4 testing already have been granted market approval but remain under FDA review for potential safety risks. But, he said, “I don't think the FDA is talking about really making Phase 4 tougher.”
Hamburg said placing additional requirements on the FDA in terms of its oversight responsibilities will increase the demands on the already overstretched FDA staff, hampering the review process.
The bill would require the FDA to incorporate patient-reported outcome data within its review process to assess a drug's benefits and its tolerable risks. And it calls for additional funding for the National Institutes of Health, although it does not specify the funding level. The bill also would expedite the review process for vaccines.
Gregory Daniel, managing director for evidence development and innovation at the Brookings Institution's Center for Health Policy, said the bill needs more detail, particularly on funding levels. “All of this together seems to be going in the right direction toward ensuring that patients have the opportunity to receive really important therapies that address unmet need as quickly as possible,” he said.
Caplan guardedly favors the bill's encouragement of broader use of surrogate endpoints, which the FDA already uses to predict the likely clinical outcome of a treatment earlier in its review process without spending the years or decades it could take to observe actual patient outcomes. Though useful, Caplan warned that surrogate endpoints cannot fully predict the long-term risks of a drug. “You get speed, and that's good,” he said. “But you up the risk.”
One of the most controversial provisions of the bill would offer incentives for drugmakers to develop innovative therapies by extending by several years the length of time their products would have market exclusivity.
Manufacturers would be able to apply for up to 15 years of patent protection for a product if it was intended to treat “one or more unmet needs.” Currently new biologic drugs can receive a maximum of 12 years of market exclusivity, with five years for new chemical drugs and seven years for orphan drugs.
Allowing longer market exclusivity for such a broadly defined category of products raises the possibility that most new drugs would qualify for patent protection, critics say. That could force consumers and payers to wait longer before having access to cheaper generic alternatives, driving up costs.
But Brookings' Daniel said market exclusivity in areas of unmet need might offer needed investment incentives. The bill's other proposed reforms would “facilitate smaller, faster, smarter clinical trials that get these potentially curative, higher-cost medications on the market quicker, and that will force a lot of new ways of thinking about value.” He said the healthcare system should not be looking at the sticker price of a drug, but “at what value can that particular therapy bring to treating a patient.”