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).
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
| “Establishing new ways of developing safe and effective new antibacterial drugs is an enormous challenge and not an effort that can be accomplished alone.” |
—Edward Cox, M.D., M.P.H., director of the Office of Antimicrobial Products in FDA’s Center for Drug Evaluation and Research, announcing the creation of the Antibacterial Drug Development Task Force under GAIN
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.
In the State of the Union address, President Barack Obama recognized the need to “stay ahead of drug-resistant bacteria” and that developing therapies to fight these threats is an opportunity for American innovation and discovery. The threat of drug-resistant bacteria is real, and the need for antibiotic development clear.More info
A bipartisan group of representatives introduced in the U.S. House of Representatives a bill that would create an accelerated approval pathway for antibiotics and antifungals for use in limited populations and would update the criteria that HHS uses to determine breakpoints for drugs.More info
Letter from Pew Thanking Representatives Gingrey and Green for Leadership on New Antibiotics LegislationRepresentatives Phil Gingrey (R-GA) and Gene Green (D-TX) introduced legislation intended to bring antibiotics to patients with few other treatment options. In a letter, Pew called the bill, named the Antibiotic Development to Advance Patient Treatment (ADAPT) Act, “a welcome step towards establishing a new regulatory pathway to bring desperately-needed antibiotics to the patients who need them the most.” More info
Last spring, Arjun Srinivasan, an associate director of the CDC, delivered a presentation to state health officials with some alarming information. Before the year 2000, he said, it was rare to find cases of bacteria resistant to carbapenems, a class of powerful, last-resort antibiotics. But by February 2013 they had been seen in almost every state. On March 5, Thomas Frieden, director of the CDC, issued a public warning about “nightmare” bacteria, a family of germs known as CREs. They can kill up to half the patients who get bloodstream infections from them, resist most or all antibiotics and spread resistance to other strains.More info
"On Sept 16, the US Centers for Disease Control and Prevention (CDC) released its report Antibiotic Resistance Threats in the United States, 2013 —their first ever reporton this subject. From the outset the tone is clear: in his foreword, Tom Frieden, director of the CDC, states that "antimicrobial resistance is one of our most serious health threats. Infections from resistant bacteria are now too common." The stated aim of this report is to increase awareness of the threat resistance poses and to encourage immediat e action to address this threat."More info
"A recent report from the Centers for Disease Control and Prevention is adding urgency to an issue lawmakers from both parties say they want to address: the rise of bacteria that are resistant to antibiotics."More info
A major report from the U.S. Centers for Disease Control and Prevention, Antibiotic Resistance Threats to the United States, 2013, confirms the growing danger of drug resistance.More info
In July 2013, The Pew Charitable Trusts and the Infectious Disease Society of America put forth a set of principles supporting the creation of a new regulatory pathway for antibiotics that target special or limited populations. Once in place, the pathway for limited population antibacterial drugs (LPAD) would expedite patient access to critically-needed antibiotics to treat serious or life-threatening infections for which there are currently inadequate treatment options.More info
Pew and the Infectious Diseases Society of America applaud Senators Michael Bennet (D-CO) and Orrin Hatch (R-UT) for their leadership in supporting the creation of the Limited Population Antibacterial Drug (LPAD) pathway. Once put in place, LPAD would expedite patient access to critically-needed antibiotics to treat serious or life-threatening infections for which there are currently inadequate treatment options.More info
Pew and the Infectious Diseases Society of America applaud U.S. Representatives Phil Gingrey (R-GA) and Gene Green (D-TX) for their leadership in supporting the creation of the Limited Population Antibacterial Drug (LPAD) pathway. Once put in place, LPAD would expedite patient access to critically-needed antibiotics to treat serious or life-threatening infections for which there are currently inadequate treatment options.More info