The Food & Drug Administration made a propitious start for this New Year. Right on deadline, the agency produced recommendations
for the Prescription Drug User Fee Act (PDUFA) and two programs governing the fees the biomedical industry pays to fund the
regulation of prescription drugs, generics, and biologics. FDA stayed in the spotlight last month when Commissioner Margaret
Hamburg testified before Congress.
The next series of hurdles is unlikely to be as propitious. Hamburg and her staff must begin to fix a drug approval process
many patients, doctors, drug developers, and investors—even regulators—consider to be in need of repair. Inefficiency at this
agency has profound consequences: foremost to public health, and also to our country's ability to maintain our global leadership
in drug development.
Let me be clear: The problems I'm discussing have nothing to do with the work ethic or talent at FDA. To the contrary, I've
dealt with dozens of smart, hard-working staff members there over the years who are dedicated to improving public health.
But even with the best intentions, regulators are stymied by deeply flawed processes and systems. To name a few:
No fixed term at the top.
FDA has had five commissioners in the past 10 years alone. How can we expect effective leadership when the commissioner changes
every couple of years, subject to political whims? A fixed term of, say, six years, would go a long way to correcting this
Seemingly capricious decision-making.
Too many companies developing new drugs run aground when the rules change or the goal posts shift at the eleventh hour. In
2006, the FDA surprised three companies presenting at an advisory committee meeting on their antibiotics for bacterial sinusitis
or community-acquired pneumonia. The companies had spent millions of dollars and years of effort on their clinical trials
based on previously accepted standards—and now, the standards have changed. All of the drugs were rejected and all three companies
went out of business.
Even when a procedural change is legitimate, information often fails to reach companies with drugs under review. It is also
difficult to have any informal exchanges with FDA, so that even questions that might readily be addressed in a phone call
can require months of waiting for a formal meeting or conference call to be scheduled. Meanwhile, drug development programs
All stakeholders in healthcare agree that patient safety is paramount. But the balance of benefit versus risk at the FDA
has moved dramatically toward risk aversion. No surprise here. With the media sensationalizing the risks not just of medications
but of everything from drinking water to tricycles, and Congress grilling FDA staffers repeatedly before the cameras, regulators
have received a clear message: the safest route is to heap on new requirements and delay approvals. Yet the risks of delaying
patient access to drugs that might help them are not taken into account.
Narrow application of accelerated approval.
FDA has the ability to speed approval of new medications that address serious conditions with unmet medical needs. However,
accelerated approval has been applied primarily to drugs for HIV and cancer, while many other serious conditions don't benefit
from this process.
Too little patient input.
Congress often hears from patients desperate to see new drugs approved, but their voices don't carry significant weight in
the review process.
No advocacy for innovation.
The U.S. has the world's most nimble infrastructure for medical advancements, but at FDA there is no mandate to promote innovation.
FDA's mission statement should highlight the importance of innovation, and a Chief Innovation Officer should be appointed
to ensure that FDA processes take this into account.
Biotech companies have grown increasingly alarmed by the impact of these regulatory shortcomings. A survey of biomedical CEOs
in California released last month shows that eight in 10 CEOs believe the FDA approval process is slowing growth of their
companies and threatens growth in the medical technology sector. Three-quarters of those surveyed said problems at the agency
place U.S. biomedical leadership in jeopardy.
Another influential constituency is voting with its feet: venture capitalists who, historically, have funded small companies
developing many of the most promising experimental drugs. Last fall, the National Venture Capital Association (NVCA) and its
partner organization, the Medical Innovation and Competitiveness Coalition, released a survey of 156 VC firms that account
for about $10 billion in venture backing for medical startups. Thirty-nine percent said they had cut spending on life sciences
in recent years, and another 39 percent expected to do so in the future. Asked why, nearly two-thirds of companies cited regulatory
uncertainty and risk-aversion at FDA. Eighty-six percent said that, in coming years, first commercialization of some products
they backed would occur in other countries.
It's also troubling that many respondents said they expected to see investments in treatments for diabetes and obesity plummet.
These are two of the biggest contributors to healthcare costs, morbidities, and death in this country. Yet it's easy to see
why investors would head for the exits. FDA has rejected three obesity drugs in the past six years, one of which was recommended
by the agency's own advisory panel. At the same time, FDA has markedly increased the requirements for demonstrating cardiovascular
safety of new drugs for diabetes.