Scientists and public health officials around the world are working to counter the threats posed by increasingly hard-to-treat, drug-resistant bacteria. In the U.S., the Food and Drug Administration plays a crucial role in efforts to protect human and animal health and to safeguard the nation’s food supply. Dr. Scott Gottlieb, the FDA commissioner, outlined the agency’s plans to combat antibiotic resistance in September in a speech at The Pew Charitable Trusts.
A physician and health policy expert, Gottlieb has served as commissioner since May 2017. He previously was the agency’s deputy commissioner for medical and scientific affairs and earlier was a senior adviser to the commissioner. Gottlieb recently answered questions from Pew about the threat of antimicrobial-resistant bacteria and the work FDA is doing to fight superbugs.
A: Our regulatory responsibilities put us in a key position to help coordinate and advance U.S. efforts to combat antimicrobial resistance (AMR). Our role is to promote and protect the public health by ensuring the safety, efficacy, and security of medical products and the safety of our nation’s food supply. In the context of product development, we often talk about a continuous product life cycle approach. From pre-market product development to post-market safety surveillance, FDA works to ensure that products are safe and effective for their intended use for as long as they remain on the market. In this effort, FDA uses a comprehensive approach with four major components that address the full continuum of product development and use: facilitating product development, promoting product stewardship, supporting antimicrobial resistance surveillance, and advancing regulatory science (the science of developing new tools, standards, and approaches to assess all FDA-regulated products).
These components are implemented by four centers within FDA, each of which has a tailored role. For example, FDA’s Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research lead agency efforts to bring new small molecule antimicrobials and nontraditional products to market, while the Center for Devices and Radiological Health focuses on new diagnostic devices that can help rapidly identify the cause of an infection so that appropriate therapy can be provided to the patient. Our Center for Veterinary Medicine plays a role in all aspects of the product life cycle, especially when it comes to advancing stewardship efforts in veterinary settings.
A: Because of the pressing public health need for antibiotics that can defeat increasingly resistant types of bacteria, laws have been passed in recent Congresses to help FDA strengthen the antimicrobial drug development pipeline. In 2012, Congress passed the Generating Antibiotic Incentives Now [GAIN] Act, which created incentives for bringing “qualified infectious disease products” (QIDP) to market. These are defined as antibacterial and antifungal drugs for human use intended to treat serious or life-threatening infections. FDA has been working diligently to implement this law. Since 2012, FDA has awarded 169 QIDP designations, and to date, 15 of those have been approved. FDA has additionally issued guidance documents to support drug developers bringing these critically important products to market.
Additionally, Congress established a new pathway under the 21st Century Cures Act called the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) for certain antibacterial or antifungal drugs that treat serious or life-threating infections in limited populations of patients with unmet medical needs. LPAD provides FDA with tools to help ensure that health care providers understand the limited population for which the drug was shown to be safe and effective. These tools include required labeling to identify the products as LPAD drugs and submission of promotional material before dissemination.
An important component of our work is collaborating with stakeholders and researchers. We have held workshops and advisory committee meetings to discuss development pathways and engage stakeholders in the area of antibacterial drug development. These discussions have helped to develop the science described in our guidance documents. We have also been commissioning research on general issues in challenging areas of antibacterial drug development. That includes development of animal models of Pseudomonas aeruginosa and Acinetobacter baumannii infections; establishing endpoints for clinical trials of drugs for the treatment of community-acquired bacterial pneumonia, acute bacterial skin infections, and hospital-acquired bacterial pneumonia; and exploring the use of the data from medical records to assess and update in vitro susceptibility test interpretive criteria (what are known as breakpoints). Breakpoints provide information to help doctors determine which antibacterial drugs will be most effective in treating a given bacterial infection.
A: GAIN authorizes FDA to provide a five-year extension of exclusivity to certain QIDPs, and that extension is additive to any other exclusivity that the application qualifies for. The draft guidance is intended to reduce uncertainty about this incentive by providing additional clarity on FDA’s policies and procedures related to QIDP designation and responds to common questions that sponsors might have throughout the development process.
A: The FDA webpage, which lists FDA recognized breakpoints, will help us keep this data up to date. Previously, the process for maintaining breakpoints was based on trying to keep the drug labeling for each antibacterial or antifungal product current. It was clear that a more centralized approach was needed. Physicians treating these serious infections must have up-to-date breakpoints so they can select the best treatment for their patient’s infection. Even if the physician cannot determine the exact treatment from breakpoint information, they may be able to identify that a narrow-spectrum drug is still effective based on up-to-date information, rather than a broader-spectrum drug or a drug reserved for use when resistance to other options is identified or suspected. Additionally, breakpoints are critical to infection control because they help identify patients with resistant bacteria where certain infection control measures should be in place to prevent spread of the resistant organisms to others.
A: AMR is a challenging and complex problem. Physicians, scientists, industry, and governments across the world are working on this issue together. The problem has never been one that any one entity or country could address, and it never will be.
What makes this moment different and gives me hope that we can get control over this issue is that we are at an inflection point in science and innovation. We also have an opportunity now to look at how we have addressed the issue in the past and determine other ways we can address this problem—whether that be investment in research, improving our utilization of data collection through electronic health records and hospital reporting, additional guidance for industry developing these products, appropriate incentives to reward innovators for these critical products, or assessing payment models that could better suit the appropriate utilization and stewardship of these products.