For several months, the US Food and Drug Administration (FDA) has been seeking public input on a proposed rule that would establish a list of "qualifying pathogens" under a provision of the FDA Safety and Innovation Act (FDASIA) that is intended to help spur the development of new antibiotics. Now, after an extensive input process, FDA is out with a proposed rule establishing that list.
The provision is more commonly known as the Generating Antibiotics Incentives Now (GAIN) Act, and follows years of legislators and public health officials sounding the alarm about the dearth of new antibiotics under development, even as drug-resistant versions of many pathogens take hold around the globe.
While legislators were clear about some of the provisions for products under the GAIN Act-namely, the incentives to be given to products that qualify for GAIN status-they were considerably more ambiguous about which pathogens would qualify a product for the program. Under Section 505E, developers would be given five years of additional market-based exclusivity incentives if they develop products for a "qualified infectious disease."
Thus, FDA had to answer a question before the pathway could be established: What is a "qualified infectious disease" under the GAIN Act?
The statute laid out some, but not all, qualifications. For example, a "qualifying pathogen" had to be one with the "potential to pose a serious threat to public health." Legislators had identified gram-positive pathogens, multi-drug resistant gram-negative bacteria, multi-drug resistant tuberculosis (TB) and Clostridium difficile (c-diff) as being definite additions to the list, but left it up to FDA to generate a more exhaustive one.
FDA had three questions for industry when it held a meeting in December 2012:
- How should FDA determine which pathogens are eligible for incentives under the GAIN Act?
- Should FDA consider any other factors in making its determinations about incentives?
- Which specific pathogens should be eligible for inclusion on FDA's list of qualified infectious diseases?
Industry Responds: Flexibility Needed, Please
Industry responded to FDA's questions by pleading with the agency for a flexible framework, noting that pathogens can emerge rapidly and require nimble development frameworks to promote suitable treatments.
Pfizer, for example, proposed that the list be flexible, allowing for rapid updates if necessary. "The changing nature of microbial pathogens of public health importance requires a process that allows the accurate and timely modification and updating of this list," the company wrote in a submission to FDA's federal docket. "Since GAIN was enacted, two new bacterial pathogens … have emerged and are well recognized by experts in the field as significant public health threats." Without the ability to quickly update the list, Pfizer said, it would not be especially useful for combating the fast-changing pathogens that threaten society.
Another company, Cubist Pharmaceuticals, an antibiotics manufacturer, mirrored Pfizer's concerns, noting that antibiotics are "wasting assets" that are only good for as long as pathogens do not become resistant to them. As a result, a continually updated list of pathogens is essential, it said, reflecting "the latest epidemiological data and clinical concerns."
Both companies seemed to favor an approach built upon a third party-the Centers for Disease Control and Prevention (CDC)-maintaining and updating the list to be current with emerging threats.
Other presenters at the meeting also called for FDA to grant some pathogens "Qualifying" status based on the ease with which they confer antibiotic resistance to other pathogens, noting that FDA needs to be proactive when it comes to the potential for certain pathogens to become resistant in the near future. Another comment called for fungus- and mold-based diseases to be added to the list, noting that such organisms also demonstrate increasing levels of drug resistance.
Qualifying Pathogens List
FDA's proposed rule seems to avoid answering those considerations in clear terms, opting instead for a lengthy list of qualifying pathogens-18 in all-that it notes is something of a starting point, with other diseases being able to be added later on if necessary.
Those qualifying pathogens are as follows:
- Acinetobacter species
- Aspergillus species
- Burkholderia cepacia complex
- Campylobacter species
- Candida species
- Clostridium difficile
- Enterococcus species
- Mycobacterium tuberculosis complex
- Neisseria gonorrhoeae
- Neisseria meningitidis
- non-tuberculous mycobacteria species
- Pseudomonas species.
- Staphylococcus aureus
- Streptococcus agalactiae
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Vibrio cholerae
Comments on the proposed rule may be submitted to FDA within 60 days.
FDA: Establishing List of Qualifying Pathogens under the Food and Drug Administration Safety and Innovation Act