May 19, 2023
The National Center for Health Research (NCHR) appreciates the opportunity to submit public comments on the Food and Drug Administration (FDA) Draft Guidance Evaluating the Safety of Antimicrobial New Animal Drugs With Regard to Their Microbiological Effects on Bacteria of Human Health Concern.
NCHR is a non-profit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.
We support the proposed criteria for ranking drugs according to their importance to human medicine; however these criteria need to be applied correctly. We recommend the following revisions to improve the guidance:
- FDA should classify bacitracin as medically important.
Bacitracin is used topically on the skin, in the eyes, and for postoperative prophylaxis, as well as orally for treatment of human Clostridium difficile infections. This antibiotic should be considered medically important under proposed criterion number 3 in the Draft Guidance. Criterion 3 covers: “Drugs from an antimicrobial class that are NOT the sole or one of limited available therapies to treat non-serious bacterial infections in humans; that is, drugs from more than a few antimicrobial classes are available.” The Draft Guidance ranks drugs meeting criterion 3 as “medically important.” Despite its use in human medicine and fulfillment of criterion 3, the Draft Guidance ranks the antimicrobial bacitracin as non-medically important and should be revised.
2. FDA should almost always give antibiotics belonging to the same drug class the same rankings of medical importance.
The FDA should use greater caution when considering ranking subclasses of a drug differently than its overall class. In most cases, subclasses of specific drugs should not be ranked by varying degrees of importance. While this approach may be acceptable for certain drug classes such as penicillins, this approach would not be appropriate for other classes of drugs, such as macrolides. Cross-resistance and co-resistance necessitate the same rankings of medical importance for antibiotics in the same drug class because antibiotics of lesser human importance in food-producing animals can potentially lead to the emergence and selection of bacteria resistant to antibiotics of greater importance. That’s why risk management steps based on the drug of lesser importance will not be adequate in ensuring human safety.
3. The final Guidance should specify clear timelines for its implementation.
Given the importance of the need to reduce antibiotic resistance, the FDA should swiftly update and implement the new methods for ranking drugs. This should be finished within a year. Additionally, future updates to the list of medically important antimicrobials should be much more frequent. The previous update was in 2003; a 20-year gap is unacceptable. Updates should occur every five years or less, depending on the emergence of significant data.
The current draft of this guidance fails to adequately take into account co-resistance and cross-class selection for resistance. As a result, its determination of where human health risks are greatest is fatally flawed. Our recommended revisions are essential to reduce the public health threat from antibiotic resistance related to antibiotic use in food production.