The FDA: Balancing innovation and safety

If you talk about the need to speed up the approval process for new drugs and devices, the U.S. Food and Drug Administration is often the first criticized for the time lag to new treatments. But, as the Partnering for Cures session, “What You Probably Don’t Know about Innovation at FDA” made clear, the agency is trying to become more innovative and approve new treatments more quickly and efficiently, but there are obstacles.

The biggest danger, said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, is “where public criticism and controversy outweigh science.” Deliberations should be made based on the latest science, she said, but controversy affects how the agency works and creates what she called a “circling of the wagons,” a “let’s not be too innovative” mindset.

She noted that the agency approved 10 cancer drugs in the last fiscal year and is on track to do so again this year, but it is work the FDA should not be doing alone. “It is the job of the larger biomedical community in concert with FDA” to get new drugs on the market, she said.

Some drug makers are wary of using innovative approaches with the FDA. “Once we get to the clinical study, if we want to be innovative, we have to do the traditional approach alongside, sort of carrying two tracks to get the product to market,” said Joseph DeGeorge of Merck Research Laboratories.

Many challenges to new drug approval start well before a drug finds its way to the FDA. Jonathan Leff of Warburg Pincus noted that venture capital investment in life sciences has been decreasing dramatically, and in the first nine months of this year, the number of first-time companies receiving venture capital investment was the lowest it has been since 1995. Those venture capital firms that are investing, he added, are shifting their investments to other countries or in less innovative products. “We have tremendous opportunity to translate science that is happening into cures, but the system isn’t working as well as it needs to,” he said. “We are not getting the throughput. We need to address the issues of translating scientific discoveries to new therapies.”

Some stakeholders are finding ways to assist the FDA in the process. Richard Insel of JDRF said his organization decided it had a role in educating the agency in novel treatments and their development. And when JDRF wanted to work on an artificial pancreas, there was no regulatory guidance. So with the FDA’s knowledge, the group convened opinion leaders and created draft guidance that was submitted to the FDA. This helped the FDA draft its own regulatory guidance for the artificial pancreas, which just came out in final form.

Frank Douglas with Austen BioInnovation Institute said his organization decided to bring the FDA in earlier in the process and found that things went smoother. “We spent a lot of time trying to figure out how to approach the FDA to make them feel they were in a safe harbor for collaboration,” he said.

The panelists agreed that bringing patient foundations, as well as the patients and families, into the regulatory process to discuss risks and benefits of individual drugs is vital. “We need to hear from affected communities about what tradeoffs they think are acceptable,” said Woodcock. “That should be our guiding light.”

So what would help the FDA improve the process, moderator Margaret Anderson of FasterCures asked the group.

The innovative spirit that is evident at the highest levels of the FDA need to be transitioned to the practitioners of the review process, said Insel.

Douglas noted that as the FDA collaborates more, it should identify other bodies that can be brought in to help with reviews.

Woodcock noted that the workload at the FDA continues to be a problem. It is hard to feel innovative when you are facing a mountain of paperwork, she said.

Anderson noted that the Alliance for a Stronger FDA, which she urged attendees to support, is focused on increasing the agency’s budget.

One panelist answered the question with praise. “The FDA environment, in terms of helping to advance and stimulate innovation, is better today than it has been in a while, and that is a credit to the leadership,” said Leff.

Keeping pace with globalization: A question of public health

One-quarter of every dollar spent in this country goes to products regulated by the U.S. Food and Drug Administration (FDA). Think about that for a minute. Every meal you eat, every medicine you take, every cosmetic you use, even the food you feed your pet was vetted for safety by FDA experts. But in an increasingly globalized world, the agency’s responsibilities are quickly outpacing its resources.

In addition to all the food, drugs, biologics, medical devices, cosmetics, dietary supplements, and veterinary products made in the United States, FDA also regulates products coming into the U.S. from more than 300,000 facilities in 150 countries around the world.

However, we could be heading toward some risky compromises– and fast. Consider this:

• 80 percent of the active pharmaceutical ingredients in medications sold in the U.S. are manufactured elsewhere.
• Nearly two-thirds of the fruits and vegetables consumed domestically come from outside of this country.
• Half of all medical devices used in the U.S. are imported.
• Food and medical device imports are growing by an average of 10 percent per year, and pharmaceutical product imports are increasing by nearly 13 percent per year.

“While foreign manufacturing facilities have increased dramatically, FDA’s budget and staffing have remained consistent,” noted Marcie McClintic Coates of Mylan, one of the largest generics and specialty pharmaceutical companies in the world, at a Capitol Hill briefing that FasterCures Executive Director Margaret Anderson moderated earlier this week. “Because their resources for international inspections are so limited, FDA has not visited some of our facilities in more than nine years.”

Panelist Ron Guido of Johnson & Johnson pointed out that counterfeiting is the largest growing industry in the world and the crime of 21st century. “Up to 10 percent of the pharmaceuticals coming to the U.S. may be counterfeit. To put that into perspective, 1 percent equals 40 million prescriptions.”

The challenges of globalization are perhaps most visible in the food industry. “Food imports have almost doubled in the past 10 years,” said Caroline Smith DeWaal of the Center for Science in the Public Interest, “and FDA doesn’t have the capacity or inspection structure to keep up with the needs of consumers, which raises frightening possibilities.”

Congress has passed two new laws aimed at helping FDA handle its responsibilities: The Food and Safety Modernization Act and the Food and Drug Administration Safety and Innovation Act. But the agency is not yet receiving adequate funds to implement either law. And sequestration would further compromise FDA’s public health mission, making an already tenuous situation worse. 

For a resource-intensive agency that spends 80 percent of its budget on people (inspectors, researchers, etc.), cuts could have especially far-reaching effects, impacting the products we use every day and expect to be safe and effective. Even though the agency collaborates with foreign governments, “there is no inspection like an FDA inspection,” noted McClintic. “The bar is higher.”

For more information on strengthening the FDA, visit the Alliance for a Stronger FDA at: http://strengthenfda.org/

The FDA's To-Do List

by Margaret Anderson, COO, FasterCures

The U.S. Food and Drug Administration’s priority to-do list is long. Dr. Joshus Sharfstein, FDA's Principal Deputy Commisioner spent some time recently addressing the list with members of the Alliance for a Stronger FDA. At the top of the list was transparency, a critical priority and one that the agency is addressing through a Task Force dedicated to delve deeper into this area. Also on the list were credibility, standards, global supply chain, guidance, integrity, enforcement. FDA’s credibility is of paramount importance, without it the medical research enterprise and health care delivery system will come to a grinding halt. "If we can successfully build something with all these strands together it will be more than the sum of its parts."

I asked about how the agency can work more closely with companies so there is more predictability. We’ve all heard stories of promising compounds languishing because the regulatory hurdles were high and in the end, the patients pay the ultimate price if that promise sits idle.

The expansion of the agency’s commitment to advance regulatory science spans work in the Critical Path shop, the Reagan-Udall Foundation (of which FasterCures is a recent supporter), and a list of key science areas that could make a big difference in the markers of whether something works. In order for the baton to be passed from NIH-funded work to translation at companies into products, the FDA needs to be ahead of the innovation curve. Sounds like the topic is clearly on the to-do list.

The Alliance for a Stronger FDA has made a huge difference in the FDA’s funding levels. Its only goal is to get the agency more appropriated dollars and I 'm proud to be a Board member. If your organization is not a member, I urge you to get engaged. The agency’s funding situation has improved, but we have a long way to go to ensure FDA gets to where it wants to be vis-à-vis innovation in all areas, but particularly in medical research.

Which makes FasterCures' Partnering for Cures meeting all the more timely and relevant. To be held December 1-3 in New York, we're bringing together medical research leaders, investors, and decision-makers, including Dr. Sharfstein, to explore innovative approaches to pursuing high-risk, long-term investments that could lead to therapeutic breakthroughs. Joining Dr. Sharfstein on the speaker roster are some of the most forward-thinking leaders in medical research: Pfizer CEO Jeffrey Kindler, Cystic Fibrosis Foundation's Bob Beall, NIAID's Anthony S. Fauci, Harvard Stem Cell Institute's Doug Melton. The list goes on...but what I think is most interesting is the coming together of sectors to explore partnerships needed to turn a scientific discovery into a viable therapeutic option. Learn more and be a part of this first-of-its-kind effort: http://www.partneringforcures.org.