Senators found much to praise at the FDA, but the pace of progress and recent controversial drug approval decisions raised more than a few eyebrows at a Senate Health, Education, Labor and Pensions (HELP) Committee hearing Thursday.

FDA Commissioner Margaret Hamburg found herself defending the agency’s approval of Zohydro, a pure form of hydrocodone, and reminding the lawmakers of the current limits of evolving regulatory science. She also dismissed industry claims that the FDA was lagging behind other countries as “urban mythology.”

The FDA has come under repeated fire from lawmakers and advocacy groups for approving Zogenix Inc.’s Zohydro ER last year as a Schedule II painkiller after an advisory committee voted 11-2 against approval because the drug was not abuse-deterrent. (See BioWorld Today, Dec. 10, 2012, and Oct. 30, 2013.)

HELP Chairman Tom Harkin (D-Iowa) raised the issue at the hearing, noting the growing epidemic of prescription drug abuse and Americans’ increasing reliance on painkillers. In 2002, doctors wrote 144 million prescriptions for pain drugs, Harkin said. That number had climbed to 241 million in 2012. Meanwhile, the number of people dying from prescription drug overdoses is escalating, with more than 16,000 deaths reported in 2014.

Prescription drug abuse also leads to other types of drug abuse, Sen. Robert Casey (D-Pa.) said, pointing out that people who abuse prescription drugs are 19 times more likely to abuse heroin.

Despite its potential for abuse, hydrocodone is the most prescribed drug in the U.S., which accounts for 99 percent of the world consumption of the painkiller, Harkin said. “I didn’t realize we were so painful in this country,” he added.

When asked how the FDA could approve Zohydro given the current epidemic of prescription drug abuse, Hamburg responded that the agency has to ensure patients have the drugs they need while balancing concerns about safety and abuse.

Other approved hydrocodone products contain acetaminophen, which can lead to liver toxicity. Increasing the dosage of such drugs raises the danger of liver damage. Thus, a pure form of hydrocodone was needed, she said.

Advocacy groups and public health officials expect drugs such as Zohydro to have abuse-deterrent mechanisms. Sen. Michael Enzi (R-Wyo.) said sponsors of opioids are stymied and confused by the agency’s lack of standards for abuse deterrence.

The technology is poor, Hamburg said, so it does no good to label an opioid as abuse-deterrent when it really isn’t. While the FDA is working on guidance on the subject, the science and technology need to be developed first, she noted. Industry also could help by developing non-opioid painkillers.

As for the Anesthetic and Analgesic Drug Products Advisory Committee’s recommendation to reject Zohydro, Hamburg said that vote came before the FDA put more stringent labeling requirements in place. She also reminded the senators that adcom votes are advisory, not determinative.

Several lawmakers have asked Health and Human Services Secretary Kathleen Sebelius to overturn the approval. In the most recent request, Sen. Joe Manchin (D-W.Va.) suggested a link between the approval and industry “pay-to-play” meetings with FDA officials at conferences. He met with Hamburg before the hearing to discuss his dismay about the agency’s action and his concerns about the pending launch of the drug. (See BioWorld Today, Nov. 27, 2013.)

Manchin has voiced concerns about hydrocodone products in the past. When Congress was crafting the FDA Safety and Innovation Act (FDASIA), he pushed for an amendment to move hydrocodone drugs from Schedule III to Schedule II controlled substances. The amendment was included in the Senate bill, but it was cut from the final bill that reconciled the Senate and House provisions after the Generic Pharmaceutical Association objected to it, claiming it would restrict access and increase prices for the pain drugs. (See BioWorld Today, June 27, 2012.)

During the HELP hearing, Enzi also echoed industry concerns that the FDA was lagging behind other countries in keeping up with science in terms of innovation, new clinical trial designs and endpoints. As a case in point, he mentioned the FDA’s rejection last year of Genzyme Corp.’s multiple sclerosis (MS) drug Lemtrada (alemtuzumab), which had been approved in the EU and several other countries. (See BioWorld Today, Dec. 31, 2013.)

Dismissing the industry claims as urban mythology, Hamburg said the FDA is on the cutting edge, leading other countries in terms of innovative drug approvals, and it’s on a par with medical device approvals. She declined to comment on why the MS drug wasn’t approved, saying that was proprietary information.

AGENCY IN TRANSFORMATION

Shifting the focus to the agency’s accomplishments, Hamburg said the FDA is streamlining and modernizing its regulatory programs to minimize regulatory uncertainty for the industry. In the past few years, the agency has undergone a huge transformation as it took on new responsibilities.

In response to hints of mild impatience with the agency’s slow progress on biosimilars and other programs, Hamburg noted the challenges the FDA faces as it tries to implement all its new authorities with limited funds. FDASIA alone required the agency to promulgate more than 30 rules and 40 guidances, put together more than 20 reports for Congress and complete several other deliverables.

“Implementing FDASIA is a considerable undertaking, requiring detailed planning to integrate these tasks with the rest of FDA’s workload,” she said in her written testimony.

For instance, as a result of the Generating Antibiotic Incentives Now provisions in FDASIA, the FDA has designated 40 drug candidates, representing 27 unique molecules, as qualified infectious disease products since July 2012. The ones that are approved will enjoy additional market exclusivity.

The agency also has been busy with FDASIA’s breakthrough drug designation. As of Dec. 31, it had received 121 requests for the designation and had granted it to 36 candidates that showed encouraging early clinical results in areas such as cystic fibrosis and breast cancer. It has approved two breakthrough therapies for rare types of cancer and one for hepatitis C, Hamburg said.