On July 9, 2012, the Generating Antibiotic Incentives Now, or GAIN, provisions were signed into law by President Barack Obama as part of the Food and Drug Administration Safety and Innovation Act. This bipartisan legislation extends by five years the exclusivity period during which certain antibiotics—those that treat serious or life-threatening infections—can be sold without generic competition. This additional period of exclusivity increases the potential for profits from new antibiotics by giving innovative companies more time to recoup their investment costs.
Why is this legislation needed?
Antibiotics are one of the greatest success stories in modern medicine. Although we associate them with treating acute infections, they make much of modern care possible—from routine surgical procedures to organ transplants and cancer treatment.
Yet the pipeline of new antibiotics is dwindling, and a global crisis looms. Drug-resistant bacteria are spreading in our hospitals and our communities. According to a 2013 report by the Centers for Disease Control and Prevention, or CDC, more than 2 million people a year are sickened by resistant infections, and more than 23,000 die as a result.
Just when we need innovation the most, the number of new drugs to replace ineffective antibiotics is not adequate to meet patients' needs. As highlighted in a report funded by the Swedish government, many major pharmaceutical companies have abandoned their investment in developing new antibiotics and instead are focusing their resources on medicines with the potential of producing greater profits.
Bringing any new medicine to market costs hundreds of millions of dollars for basic and clinical research, including money spent on candidate drugs that do not pan out. Antibiotics generate small revenue compared with “blockbuster” drugs such as those for high blood pressure or cholesterol, which may be taken daily by millions of patients. Therefore, there is little incentive for manufacturers to develop new antibiotics.
GAIN seeks to increase antibiotics' commercial value to manufacturers by extending the term of exclusivity, or market protection, granted by FDA to innovator drugs.
What does GAIN do?
Extends the Exclusivity for New Antibiotics
GAIN grants an additional five years of exclusivity for those new antibiotics designated under the law as a “qualified infectious disease product,” defined as “an antibacterial or antifungal drug for human use intended to treat serious or life-threatening infections.” The extra five years of market protection is in addition to any existing exclusivity, including that which may be applicable under Hatch-Waxman (five years or three years), orphan drug (seven years), or pediatric exclusivity (six months).
Note: Please refer to Antibiotics Currently in Clinical Development for up-to-date information on qualified infectious disease products (QIDP).
Speeds Development and Review of New Antibiotics
Drugs that fall under the GAIN provisions receive fast track and priority review status and undergo an expedited regulatory approval process with FDA.
Requires Additional and/or Updated Clinical Trial Guidance
GAIN requires FDA to issue new guidance on the development of pathogen-focused antibiotics—those that target specific bacteria. Such advice has not been available previously, leaving drug makers with no clear development pathway for these products. The agency must also review and revise other antibiotic guidance to ensure that it is up-to-date from a scientific and regulatory perspective.
Requires Listing of Pathogens That Pose a Threat to Public Health
GAIN requires FDA to compile a list of “qualifying pathogens” that have the potential to pose a serious threat to public health and to update this list at least every five years. The agency must consult with CDC, medical care professionals, and clinical researchers in deciding which pathogens to include—taking into consideration the impact on human health and any increases in drug resistance.
Progress to date
As of October 2013, at least 16 antibiotics have been designated as qualified infectious disease products under GAIN, making them eligible for incentives such as added market protection if approved for patient use. Many of these antibiotics, however, are in the early stages of development and may not be approved for patients. However, two companies submitted marketing applications for qualified infectious disease products in late 2013 that could be eligible for approval as early as 2014.1
GAIN implementation is ongoing. To date, FDA has:
Created an Antibacterial Drug Development Task Force to develop and revise guidance for antibacterial drug development.
Released a draft list of pathogens with the potential to pose a serious threat to public health and the methodology used to generate the list.
Drafted preliminary guidance for companies developing antibiotics that address unmet needs, including drugs that are narrowly targeted or pathogen focused.
Reviewed and updated several antibacterial drug development guidance documents.
Although GAIN is an important first step in moving antibiotics safely and quickly from the laboratory to the patients who need them, the law cannot achieve that goal on its own. A new regulatory approval pathway for limited-population antibacterial drugs would encourage the development of antibiotics that address the greatest unmet needs of patients.