Editor's Note: The Animal Health Institute (AHI) represents most major animal pharmaceutical firms. In this report, AHI's leader explains how the Food and Drug Administration (FDA) has tightened rules on antibiotics.

Antibiotics used to keep food animals healthy have been the subject of headlines recently, as food-service companies have announced limits on types of antibiotics that can be used in their supply chains, and the Food and Drug Administration (FDA) removed from the market a drug used to treat sick chickens.

However, the most important development in determining future approval and use decisions was FDA's announcement of a new food safety hurdle in the approval process.

Product Safety Review

Fueled by concerns about the potential transfer of antibiotic-resistant pathogens from animals to humans, FDA is requesting sponsors or drug manufacturers perform a microbial safety review, or qualitative risk assessment, referred to as Guidance to Industry 152, for each new and currently-approved antibiotic.

Under this document, each drug will be evaluated for its potential to cause antimicrobial-resistant pathogens to emerge, and the risk of their transference to humans via meat consumption.

Depending on the assessment outcome for each antibiotic, sponsors could receive the green light of approval, face certain limitations on their product's use or be denied approval altogether.

For pork producers, it is important to understand that Guidance 152 also contains provisions that make it likely antibiotics given to whole herds or flocks through feed and water will receive extra scrutiny. Producers could see additional restrictions placed on some antibiotics, or product withdrawals.

Under Guidance 152, each drug is reviewed using three separate risk assessments:

  1. A release assessment, estimating the likelihood that antibiotic use will produce antibiotic-resistant bacteria in the animal;

  2. An exposure assessment, estimating the probability of people ingesting antibiotic-resistant bacteria derived from the meat; and

  3. A consequence assessment, assessing the chances human exposure to resistant bacteria would adversely affect human health. However, FDA already conducted this assessment for sponsors, and categorized each drug class as “critically important,” “highly important” or “important” in treating human diseases.

For instance, all fluoroquinolones, third-generation cephalosporins, macrolides, and trimeth/sulfa drugs used in animals automatically receive a “critically important” consequence assessment.

A final comprehensive risk ranking is derived by combining all three risk estimations into low, medium or high risk. Depending on risk, FDA must consider imposing specific risk management measures based on:

  • Limits on how the product can be marketed, whether with a prescription, over-the-counter or subject to veterinary feed directive;

  • Bans on extra-label drug use;

  • Extent of use limits, duration of use or route of administration;

  • Post-approval monitoring; and

  • Review by FDA's veterinary advisory committee, comprised of physicians and veterinarians.

Risk Calculation

The new policy allows sponsors to use available data to more precisely calculate risk. Quantitative risk assessment, which relies on data for risk measurements, results in a more precise risk calculation. Qualitative risk assessment provides only estimations in the absence of real data, and as a result, typically overestimates risk.

For example, Guidance 152 requires an exposure assessment rating of “high” when a hog is the target animal, because per-capita consumption of pork is “high” vs. other, less-eaten meats like fish and veal. While “high” is a relative term, only in comparison to consumption levels of other commodities, it overstates actual risk by ignoring data showing the chance of antibiotic-resistant bacteria transferring to humans via pork consumption is very low. Data exist on bacterial levels at slaughter and in retail meats, and resistant bacteria at slaughter and in retail meats. Using actual data reduces uncertainties and usually reduces the risk estimation.

The ability of companies to plug data into this safety review is one important factor in the continued approval and use of antibiotics as a tool in animal health management. Results so far are encouraging. Quantitative risk assessments done by industry and FDA show potential risks are exceedingly low.

A second factor is the antibiotic-by-antibiotic review of products to account for the differences in compounds.

These two factors — the use of data in risk assessment and individual drug review — give sponsors the opportunity to demonstrate the safety of their products to FDA.

At the end of the process, it is essential that producers provide proper and careful use of antibiotics.