Updated: FDA to Congress: Consider Changes to GAIN Act

Regulatory NewsRegulatory News | 07 February 2018 |  By 

The US Food and Drug Administration (FDA) is encouraging Congress to revisit a 2012 law that sought to encourage the development of new antibiotics, as many of the treatments qualifying for incentives under the law are approved drugs being developed with slight modifications, such as a new dosage form or indication.

The recommendation, one of three released in a five-year progress report to Congress, noted: "While improvements to existing drugs may provide some benefit to patients, the development of innovative, novel drugs is essential to addressing the antimicrobial resistance crisis and ensuring that safe and effective options are available to treat current and future patients."

An article from the Annals of Internal Medicine in 2016 found that antibiotics recently approved between 2010 and 2015 "are more expensive but have been approved without evidence of clinical superiority" when compared with earlier antibiotics.

Aaron Kesselheim, associate professor of medicine at Harvard Medical School and a faculty member in the Division of Pharmacoepidemiology and Pharmacoeconomics in the Department of Medicine at Brigham and Women’s Hospital, told Focus: "Now almost 6 years later, I don’t see any evidence that the GAIN Act has led to any change at all in the antibiotic pipeline. It’s not surprising, of course, since the main thing GAIN did was increase the minimum generic-free market exclusivity period from about 5-7 years to 10-12 years, and most new antibiotics already have at least that much time remaining on their patents."

As far as changes that could improve GAIN, Kesselheim noted: "I don’t think tweaks to the law would make it any more effective. However, if the FDA report is emphasizing that legislative drug development incentives should be designed to go to maximally innovative and clinically effective drugs rather than just any drug in which the manufacturer makes an incremental change, that’s a sensible recommendation."

And because the outpatient and inpatient antibiotics markets are not as large as say oncology or hepatitis C markets, companies may not be interested in making the research and development investments to develop new classes of antibiotics.

John Tucker, a medicinal chemist and consultant on antibiotics, told Focus: "What is needed is a completely new way of financing antibiotic drug development. Ideally, revenues would not be dependent on utilization, as we don't want to wait until a crisis of resistance creates commercial demand, nor do we want developers incentivized to maximize utilization of new antibiotics and thus resistance development. Ideally the government would simply buy out companies developing new anti-infectives that met certain pre-established criteria. I'm not sure what that would look like, but GAIN's addition of a few years of $100M per year sales isn't enough money.  Not by a long shot."

But Tucker also noted that recent progress over the last years should not be trivialized.

"The approval of new beta lactam/beta lactamase inhibitors has provided a dramatic improvement in our ability to treat multi-drug resistant infections caused by key problematic pathogens such as multi-drug resistant Enterobacteria and Pseudomonas. I frankly consider these products to be public service efforts by the industry, as they will be reserved for the most resistant of infections and the volume of use will thus be very low," he said.   


In 2012, the Generating Antibiotic Incentives Now (GAIN) Act was passed as part of the Food and Drug Administration Safety and Innovation Act (FDASIA) to encourage the development of new antibiotics, as each year at least two million people develop serious infections caused by antibiotic-resistant bacteria.

Under the GAIN Act, sponsors may request a qualified infectious disease product (QIDP) designation, which FDA reviews and responds to within 60 days of submission. Designation as a QIDP comes with five years of additional marketing exclusivity and eligibility for fast track designation and priority review.

According to the the most recent report to Congress on GAIN, from 9 July 2012 through 30 September 2017, FDA approved 12 drugs with QIDP designation and each received a priority review. The approvals came as the agency granted 147 QIDP designations, including approximately 74 designations for novel drugs.

The report to Congress follows the release of a draft questions and answers guidance intended to provide drugmakers with more clarity about QIDP, which followed a report by the Government Accountability Office criticizing FDA for not fully detailing its expectations for new antibiotics or how drugmakers could access the incentives awarded to QIDP-designated products.

In addition, on Wednesday, FDA released a revised guidance on microbiology data for systemic antibacterial drugs.


FDA, in consultation with the Centers for Disease Control and Prevention, made three recommendations in its report to Congress: Explore potential changes to GAIN, do not make any changes to the list of qualifying pathogens ("FDA will review the list within 5 years of issuance of the final rule and, if necessary, modify it by rulemaking") and more should be done to promote the development of antibacterial drugs.

"Although GAIN has contributed to facilitating the development of new antibacterial drugs, additional efforts are needed. The President’s Advisory Council on CARB (PACCARB) and groups like the Duke/Margolis Center for Health Policy are working on potential solutions to the antimicrobial resistance crisis including a focus on developing appropriate incentives to spur drug, vaccine, and related diagnostic development. Thought-leaders in the United States and Europe have discussed various push and pull incentives, including new business models for antibacterial drug development that delink the sales of these drugs from companies’ return on investments," the report says.

GAIN: Required by Section 805 of the Food and Drug Administration Safety and Innovation Act, Public Law 112-144, Department of Health and Human Services

Editor's note: Article updated on 2/8/18 with comments from Tucker and the revised guidance released Wednesday.


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