Cleveland-The Food and Drug Administration (FDA) released its long-anticipated risk-assessment guidance for food animals to
help safeguard against the emergence of antibiotic resistance in people.
Dr. Linda Tollefson, deputy director for FDA's Center for Veterinary Medicine (CVM), explains, "What this document represents
is a risk-based approach to help prevent antimicrobial resistance that may result from the use of antimicrobial drugs in food
This new approach will apply to therapeutic and non-therapeutic antimicrobial drugs intended for food-producing animals. FDA
adds that it will lead to a review of all existing approvals.
Tollefson explains that CVM has taken on many initiatives addressing the issue of antimicrobial resistance. There are many
sources of the problem, including the inappropriate use of antibiotics in people. However, this document simply represents
agriculture's role in preventing the problem, she adds.
Dr. Linda Tollefson
Industry is not disagreeing either.
According to the Animal Health Institute (AHI), a national organization representing animal health manufacturers, it's a better
approach to regulating antibiotics.
"The new guidance is a superior approach to regulating antibiotics, compared to the European phase-out of antibiotics for
growth promotion or to legislation proposed in the U.S. Congress. The new guidance bases decisions on science and risk assessment,
rather than politics, and requires drugs to be looked at individually rather than lumping them all together, AHI says.
Alexander Mathews, AHI president and CEO, says, "This risk-based approach will allow FDA to make sound management decisions
that protect public health from the potential transfer of antibiotic resistance bacteria from animals to humans. At the same
time, it will preserve the important benefits of using antibiotics to protect animal health, he adds.
Alexander S. Mathews
This new risk-assessment guidance will apply to all antibiotics approved for use in food-producing animals. FDA explains,
the guidance provides a scientific process for assessing the likelihood that an antimicrobial drug used to treat an animal
may cause an antimicrobial resistance problem in humans consuming meat or other byproducts from that animal.
"This process can help prevent antimicrobial drugs with a high risk of causing such problems from being improperly used in
food-producing animals, and thereby potentially leading to antimicrobial resistance in humans," FDA says.
The new guidance encourages drug sponsors to use a risk assessment process to demonstrate that an antimicrobial drug used
to treat food-producing animals will not create a risk of antimicrobial resistant bacteria likely to lead to human health
Stephen Sundlof, DVM, MPH, director of CVM, adds, "This guidance uses science to develop a risk-based approach to the issue
of antimicrobial resistance. It permits us to help protect human health while giving veterinarians and livestock producers
the tools they need to treat animals."
Dr. Stephen Sundlof
The agency has devised a three-part system for determining an antimicrobial drug's potential risk to humans if used to treat
food-producing animals. The three parts include:
- A "release assessment," which determines the probability that resistant bacteria will be present in an animal as a result
of the use of the new antimicrobial drug.
- An "exposure estimate" to gauge the likelihood that humans might ingest resistant bacteria.
- A "consequence assessment," which takes into account the chances human exposure to the resistant bacteria would result in
adverse human health consequences.
Once the risk estimation has been completed, it leads to a ranking of drugs: high, medium, low. These risk-based rankings
are associated with certain risk management categories.
- Category 1 (high risk estimate): strictly limited use conditions.
- Category 2 (medium risk estimate): intermediate restriction on drug use.
- Category 3 (low risk estimate): least restriction on drug use.
CVM says it also has risk management strategies for drugs that rank high. For example, an application for approval could be
flat-out denied, or approved under specific-use conditions. FDA could place limits on marketing, including prescriptions or
Veterinary Feed Directive, prohibition on extra-label use or even limits on duration/method of administration.
Included in the new document is a revised ranking system for antimicrobial drugs and their importance to human medicine.
- Critically important to human medicine: Third-generation cephalosporins, macrolides, fluoroquinolones.
- Highly important to human medicine: Fourth-generation cephalosporins, aminoglycosides, clindamycin.
- Important to human medicine: First- and second-generation cephalosporins, monobactams, quinolones.
Tollefson adds that FDA consciously decided to release this risk assessment as a guidance document rather than regulation
because it is much easier to amend due to changing science.