# Presentation: 519176

## Antimicrobial Guidance

**Food and Drug Administration’s**
**New Guidance For Industry on Antimicrobial Drugs for Food Animals**
**GFI #152**
- Released October 23, 2003

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_

- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_

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**Slide 1 of 21**

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## Pathway

- FDA issuing new policy guidance concerning issue of antimicrobial resistance:
- “***Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern***”
- Public health concern – human medical therapy may be compromised from use of antimicrobial drugs in animals

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 2 of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## Process for Developing Guidance

- 2001-2002 – drafting process
- September 2002 – first draft issued
- October 2002 – public meeting
- Late November 2002 – comment period closed

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 3 of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## Process for Developing Guidance

- January 2003 – CDER Anti Infective Drugs Committee Workshop
- March 2003 to present – revisions
- Revised document – October 2003

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 4  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

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## Description of Submitters

**Other, 27**

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- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 5  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

**Notes:**

Keep Antibiotics Working (KAW) (form letter campaign, 17388 copies)

Consumer Groups	22% (CDC helped us with a lot of these)
Food Animal Concerns Trust (FACT)
Environmental Defense Fund
Center for Science in the Public Interest (CSPI)
Sierra Club
Humane Society of the U.S. 
Animal Welfare Institute
Alliance for the Prudent Use of Antibiotics (APUA)

Producer Groups	26%
National Pork Board and National Pork Producers Council (Form letter; Nebraska Pork Board, Oklahoma Pork Board, Michigan Pork Board)
National Cattlemen’s Beef Association
National Turkey Federation

Industry	22%
Elanco, Phibro, Pfizer and the Animal Health Institute

Veterinary Groups	15%
American Veterinary Medical Association
American Association of Swine Veterinarians
American College of Poultry Veterinarians
America Association of Bovine Practitioners
Academy of Veterinary Consultants

Human Medical/ Public Health Groups	11%
Infectious Disease Society of America

Government	4%
U.S. House
U.S. Senate

STEVE:  OLA was given the task of answering the congressional letter.

## Focus of Document

- Focus: Human exposure through ingestion of animal-derived food
- Approach applies to therapeutic and non-therapeutic antimicrobial drugs intended for food-producing animals
- Will lead to review of all existing approvals

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 6  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## General Concepts

- Qualitative antimicrobial resistance risk assessment
- one possible way to evaluate human food safety with respect to antimicrobial resistance
- help determine an overall estimate of risk
- allow an informed risk management decision

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 7  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## Qualitative Risk Assessment

**Assessment**

**Qualitative Risk Assessment**

**Describes factors related to antimicrobial drug and its use in animals that contribute to the emergence of resistant bacteria or resistant determinants in the animal**

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- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 8  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## Qualitative Risk Assessment

**Assessment**

**Exposure**
**Assessment**

**Qualitative Risk Assessment**

**Describes likelihood of human exposure to  resistant bacteria or resistance determinants through animal-derived food**

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 9  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## Qualitative Risk Assessment

**Assessment**

**Exposure**
**Assessment**

**Qualitative Risk Assessment**

**Consequence**
**Assessment**

**Describes human health consequence of exposure to resistant bacteria (or determinants) based on importance of drug (or related drugs) to humans**

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 10  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## Qualitative Risk Assessment

**Assessment**

**Exposure**
**Assessment**

**Qualitative Risk Assessment**

**Consequence**
**Assessment**

**Risk Estimation**

**Risk estimation integrates results from release, exposure and consequence assessments to produce overall measure of risk associated with hazards**

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 11  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## Risk Estimation

- Integration of the results from the release assessment, exposure assessment, and consequence assessment
- Result is low, medium, or high risk for human health to be adversely impacted by emergence of antimicrobial resistance associated with the use of the drug in animals

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 12  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## Risk Management Strategies

- Risk Estimation leads to ranking of drugs as:	High, Medium, Low
- These risk-based rankings are associated with certain risk management categories

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 13  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## 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

**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

**Risk Management Strategies**

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- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ __[FDA A-Z Index ](file:///opacom/hpchoice.html)__| __[Contact FDA](file:///comments.html)__ | __[Privacy](file:///privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 14  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## Risk Management Strategies

- Applications can be either denied, or approved under specific use conditions, depending on risk
- Risk management strategies can include
- limits on marketing – Rx, Veterinary Feed Directive (equivalent of prescription feed)
- prohibition of extralabel use (use not specified on label) in accordance with 21 C.F.R. Part 530
- limits on duration/method of administration

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 15  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## New Appendix A

- New Appendix A has ranking of antimicrobial drugs according to their importance in human medicine
**revised by CDER**
- Includes NEW rankings, criteria
**High = ****CRITICALLY IMPORTANT**
**Medium**** ****= ****HIGHLY IMPORTANT**** **
**Low = ****IMPORTANT**

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 16  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

**Notes:**
While the rest of the QRA uses the rankings of  HIGH  -  MEDIUM  -  LOW, the terminology used here is Critically Important, Highly Important, and Important.  

This reflects the ongoing concern that all antimicrobials are important tools in both human and veterinary medicine.  

The flexibility of the QRA approach allows the integration of components that are ranked on different, but qualitatively, similar scales.

## New Appendix A(cont’d)

- Criteria used for ranking drugs
- Enteric pathogen responsible for foodborne disease
- Sole/limited therapy or essential therapy for serious disease
- Used to treat enteric pathogens in non-foodborne disease

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- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 17  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

**Notes:**
Appendix A, the ranking of antimicrobials drugs according to their importance in human medicine, was updated following the January ‘03 CDER Anti-infective Drugs Committee workshop.

Drugs were ranked according to these 5 criteria:
1. Whether the drug is used to treat enteric pathogens that cause food-borne disease
2. Is the drug the only available therapy to treat serous human disease
3. Is the drug used to treat enteric pathogens in non-food-borne disease
4. Cross-resistance within drug class or known linked resistance
5. Difficulty of transmitting resistance elements within or across the bacteria  species or genera 

Critically Important drugs:  Both criteria 1 AND 2
	examples: fluoroquinolones, macrolides, 3rd generation cephalosporins

Highly Important drugs:  Either criteria 1 OR 2
	examples: aminopenicillins, 4th generation cephalosporins, aminoglycosides, 		rifampin

Important: Either criteria 3, 4, OR 5
	examples: 1st & 2nd generation cephalosporins, cephamycins, monobactams

Although direct comments on Appendix A were fairly limited, concern for the ranking process was a component of many of the other comments and was the basis for us revising this section.

## New Appendix A(cont’d)

- Criteria used for ranking drugs (cont’d)
- No cross-resistance within class/no linked cross-resistance with other classes
- Limited risk of transmission of resistance elements within/across species of organisms

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| __[Contact FDA ](http://www.fda.gov/comments.html)__| __[Privacy](http://www.fda.gov/privacy.html)__ | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 18  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## Examples of drugs and their rankings

**CRITICALLY IMPORTANT**                      3rd Generation cephalosporins, macrolides, fluoroquinolones
**HIGHLY IMPORTANT**                              4th Generation cephalosporins, aminoglycosides, clindamycin
**IMPORTANT                                              **1st & 2nd Generation cephalosporins, monobactams, quinolones

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| __[FDA A-Z Index ](http://www.fda.gov/opacom/hpchoice.html)__| Contact FDA | Privacy | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 19  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## We Anticipate Success

- New regulatory pathway brings stability and transparency into the regulatory environment
- Sponsors can perform their own assessments and estimate what risk management procedures will need to be implemented to obtain approval to market their product
- Several antimicrobials assessed under the new policy have generally received a “positive” answer

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| FDA A-Z Index | Contact FDA | Privacy | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
**Slide 20  of 21     **_[Back to Slide 1](http://internet-dev.fda.gov/oc/antimicrobial/GFI.ppt)_

## www.fda.gov/cvm

**Check CVM’s Website for the most current information**

_**_____________________________________________________________________________________________________**_

- _[Text only version](http://www.fda.gov/oc/antimicrobial/gfi.html)_
- _[Press Release: Antimicrobial Animal Drugs](http://www.fda.gov/bbs/topics/NEWS/2003/NEW00964.html)_
- _[FDA Home Page ](http://www.fda.gov/default.htm)__| __[Search FDA Site ](http://www.fda.gov/search.html)__| FDA A-Z Index | Contact FDA | Privacy | __[Accessibility](http://www.hhs.gov/Accessibility.html)_
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