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Questions & Answers: Draft Revised GFI #152

Explaining the major changes since 2003 and why they were made

1. Guidance for Industry (GFI) #152 was published 20 years ago. Why is FDA updating this GFI now? 

In 2003 when GFI #152 was initially published, FDA envisioned that it would periodically reassess the rankings provided in Appendix A to ensure that the rankings reflect current prescribing practices, advances in science, and the discovery of new antimicrobial products.

2. What has been the impact of GFI #152 since its publication in 2003?

Since its publication in 2003, GFI #152 has been referenced almost exclusively as the template for sponsors preparing a microbial food safety risk assessment for review by the Agency for all original and supplemental approvals of antimicrobial new animal drugs. The framework within the guidance has led sponsors to pursue judicious and safe uses of antimicrobial new animal drugs. In most cases, these new animal drugs have been approved under the condition that the drugs be available only through the order of a licensed veterinarian for use only in limited numbers of animals by injection for treatment, control, and in a few instances, prevention of major diseases in food animals, with none approved for broad production uses in large numbers of animals for long periods of time. The guidance introduced the term “medically important” to characterize the significance and utility of classes of antimicrobial drugs in human medicine. The ranked list of drugs and classes in Appendix A was the first list of its kind and has been a blueprint for similar rankings worldwide.

3. What changes were made in the 2022 version of GFI #152 compared to the version issued in 2003?

  • Updated criteria and rankings of antimicrobial drugs used in human medicine, medically important drugs, in Appendix A,
  • New text in the “Consequence” and “Risk Estimation” sections of the guidance to address not medically important (NMI) drug products,  
  • Revisions to the “Risk Estimation” and “Risk Management Considerations” sections to include microbial food safety requirements for NMI drug products,
  • Updates to the exposure assessment tables based on extensive collaboration with the United States Department of Agriculture’s Food Safety Inspection Service (FSIS) and Economic Research Service (ERS), and 
  • Revised definitions in the “Glossary” section.

4. Why did FDA change the ranking criteria in Appendix A of GFI #152? 

In the original GFI #152, FDA weighted its ranking criteria on drugs used to treat enteric pathogens caused by food-borne disease. With improved scientific knowledge of antimicrobial resistance and medical advancements since 2003, FDA now believes the importance of an antimicrobial class should be ranked based on its use in human medicine, regardless of how a disease was transmitted. For that reason, the new criteria emphasize the utility of the drug to treat bacterial infections in humans, the seriousness of those infections, and the availability of alternative treatment options.

5. After applying the updated criteria in 2022’s revised draft GFI #152, how have the antimicrobial classes changed since 2003?

Moved from Highly Important to Critically Important:

  • Aminopenicillins
  • Aminoglycosides
  • Carbapenems
  • Doxycycline, Omadacycline, Eravacycline, and Tigecycline
  • Glycopeptides
  • Oxazolidones
  • Antimycobacterials
  • Rifamycins

Moved from Important to Highly Important:

  • Cefazolin, a 1st Generation cephalosporin
  • 2nd Generation Cephalosporin 
  • Cephamycins 

Moved from Important to Critically Important:

  • Monobactams

Quinolones were grouped with Fluoroquinolones and together, they are now classified as Critically Important.

6. Will FDA update Appendix A over time?

In response to the public feedback received on FDA’s 2020 concept paper, the agency intends to periodically reassess the rankings in Appendix A once GFI #152 has been finalized.

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