UNCLASSIFIED     PTO0648

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      SA-00    FMP-00   PRM-02   DRL-02   G-00     ALM-00   SAS-00   
        /023R

229699
SOURCE: DISKETTE.013569
DRAFTED BY: EB/TPP/ATT/ATP:USDAJFAIR/COTTE:JF/CO -- 12/04/00 202-647-1
APPROVED BY: EB/TPP/ATT:EB/TPP/ATT:MBAAS
AF/EPS:RMOLINA   EUR/ERA:GBURTON   SA/RA:DSMITH
NEA:RFLEITMAN   WHA/EPSC:MBOYNTON   EAP/EP:BLABARGE
FDA/CVM:GMITCHELL   USDA/FAS/ITP/OA:BSIMMONS
USDA/FAS/ITP/OFSTS:GYOUNG   USTR:WHOLLAND  M/SEP:CEDMUNDS
                  ------------------A7590B  041929Z /38    

R 041924Z DEC 00
FM SECSTATE WASHDC
TO ALL DIPLOMATIC AND CONSULAR POSTS
SPECIAL EMBASSY PROGRAM

UNCLAS STATE 229699 
 
SIPDIS 
 
E.O. 12958: N/A 
TAGS: EAGR ETRD
                       UNCLASSIFIED 
 
PAGE 02        STATE   229699  041926Z 
SUBJECT: FDA PROPOSAL TO WITHDRAW APPROVAL FOR USE OF 
ANTIMICROBIAL FLOUROQUINOLONE IN POULTRY 
 
¶1.  SUMMARY:   ON OCTOBER 26, 2000, THE FOOD AND DRUG 
ADMINISTRATION'S CENTER FOR VETERINARY MEDICINE PROPOSED 
WITHDRAWING ITS PREVIOUS APPROVAL FOR FLUOROQUINOLONES USED 
THERAPEUTICALLY IN POULTRY.  THE FOLLOWING IS PROVIDED TO 
ASSIST POSTS IN RESPONDING TO INQUIRIES FROM LOCAL 
GOVERNMENT OFFICIALS AND PRESS.  AS NEEDED, POSTS MAY DRAW 
ON TALKING POINTS PROVIDED IN PARA 12.  THIS IS NOT AN 
ACTION REQUEST.  FDA'S PROPOSAL AND RISK ASSESSMENT ARE 
AVAILABLE ON THE INTERNET, AS INDICATED BELOW.  IF HOST 
GOVERNMENT CONTACTS ARE INTERESTED IN ADDITIONAL 
INFORMATION, THE FDA CONTACT PERSON IS: LINDA TOLLEFSON, 
FDA/CVM, (301) 827-6647 OR LTOLLEFS@CVM.FDA.GOV.  END 
SUMMARY. 
 
BACKGROUND 
 
¶2.  THE FLUORQUINOLONE ANTIMICROBIAL DRUGS ARE USED IN 
FOOD-PRODUCING ANIMALS TO TREAT, PREVENT AND CONTROL 
DISEASE.  IN THE UNITED STATES, REGULATORY TERMINOLOGY 
NAMES THESE PRODUCTS "NEW ANIMAL DRUGS."  (NOTE: WHILE USED 
DIFFERENTLY BY SCIENTISTS, ANTIBIOTIC AND ANTIMICROBIAL ARE 
USED INTERCHANGEABLY IN THIS DOCUMENT AND MEAN A PRODUCT 
THAT HAS THE ABILITY TO INHIBIT BACTERIA.)  BEFORE ANY NEW 
ANIMAL DRUG CAN BE APPROVED IN THE UNITED STATES, THE 
DRUG'S SPONSOR MUST DEMONSTRATE THAT THE PRODUCT IS SAFE 
AND EFFECTIVE FOR ITS INTENDED USE.  IF THE ANTIMICROBIAL 
DRUG IS INTENDED FOR USE IN FOOD PRODUCING ANIMALS, THE 
DRUG SPONSOR MUST DEMONSTRATE SAFETY FOR CONSUMERS OF 
                       UNCLASSIFIED 
 
PAGE 03        STATE   229699  041926Z 
EDIBLE ANIMAL PRODUCTS, AS WELL AS SAFETY FOR USE IN THE 
ANIMAL. 
 
¶3.  THE FOOD AND DRUG ADMINISTRATION (FDA) FIRST CALLED FOR 
SEVERAL RESTRICTIONS ON ANTIMICROBIAL USE IN FEED IN 1977. 
IN RECENT YEARS, CONCERNS ABOUT THE USE OF ANTIMICROBIAL 
PRODUCTS IN FOOD-PRODUCING ANIMALS HAVE FOCUSED ON HUMAN 
FOOD SAFETY, BECAUSE FOODS OF ANIMAL ORIGIN ARE IDENTIFIED 
AS VEHICLES OF FOODBORNE DISEASE IN HUMANS. 
 
¶4.  SINCE 1988, FDA'S CENTER FOR VETERINARY MEDICINE (CVM) 
HAS APPROVED NEW THERAPEUTIC ANTIMICROBIALS AS 
PRESCRIPTION-ONLY PRODUCTS FOR USE IN FOOD-PRODUCING 
ANIMALS. THIS PRESCRIPTION-ONLY POLICY IS BASED ON THE NEED 
TO ASSURE THE PROPER USE OF ANTIMICROBIALS THROUGH PRECISE 
DIAGNOSIS AND CORRECT TREATMENT OF DISEASE TO MINIMIZE 
ANIMAL SUFFERING AND TO AVOID DRUG RESIDUES IN FOOD. 
ANTIMICROBIAL PRODUCTS FOR USE IN ANIMALS MUST MEET FDA'S 
STANDARDS FOR SAFETY, EFFICACY, AND QUALITY TO BE APPROVED 
IN THE UNITED STATES. 
 
¶5.  IN THE 1990S, SEVERAL SCIENTISTS RAISED CONCERNS ABOUT 
THE THERAPEUTIC USE OF FLUOROQUINOLONE ANTIBIOTICS IN FOOD- 
PRODUCING ANIMALS. THE SCIENTISTS SAID THE USE COULD LEAD 
TO ENTERIC DISEASE IN HUMANS ASSOCIATED WITH 
FLUOROQUINOLONE-RESISTANT FOODBORNE PATHOGENS. ADDING TO 
THAT CONCERN WERE REPORTS OF A TEMPORAL ASSOCIATION BETWEEN 
THE APPROVAL OF FLUOROQUINOLONES FOR THERAPEUTIC USE IN 
POULTRY IN EUROPE AND THE EMERGENCE OF A FLUOROQUINOLONE- 
RESISTANT CAMPYLOBACTER FROM HUMANS. 
 
                       UNCLASSIFIED 
 
PAGE 04        STATE   229699  041926Z 
¶6.  FLUOROQUINOLONES ARE CONSIDERED TO BE ONE OF THE MOST 
VALUABLE ANTIMICROBIAL DRUG CLASSES AVAILABLE TO TREAT 
HUMAN INFECTIONS BECAUSE OF THEIR SPECTRUM OF ACTIVITY, 
SAFETY, AND EASE OF ADMINISTRATION.  THIS CLASS OF DRUGS IS 
EFFECTIVE AGAINST A WIDE RANGE OF HUMAN DISEASES AND IS 
USED BOTH IN TREATMENT AND PROPHYLAXIS OF BACTERIAL 
INFECTIONS IN THE COMMUNITY AND IN HOSPITALS. 
FLUOROQUINOLONES ARE USED ROUTINELY BY PHYSICIANS FOR THE 
TREATMENT OF FOODBORNE DISEASE.  THESE DISEASES HAVE A 
MAJOR PUBLIC HEALTH CONSEQUENCE IN THE UNITED STATES. 
 
¶7.  TO FURTHER INVESTIGATE THE PUBLIC HEALTH CONCERNS 
REGARDING THE POTENTIAL IMPACT OF FLUOROQUINOLONE USE IN 
FOOD-PRODUCING ANIMALS, AND TO DETERMINE WHETHER THE 1987 
FDA REPORT (WHICH CONCLUDED THAT THERAPEUTIC ANTIMICROBIALS 
USED FOR SHORT DURATION WERE SAFE) WAS STILL VALID, FDA 
HELD A JOINT ADVISORY COMMITTEE MEETING IN 1994 THAT 
INCLUDED THE CVM VETERINARY MEDICINE ADVISORY COMMITTEE 
(VMAC) AND THE CENTER FOR DRUG EVALUATION AND RESEARCH'S 
ANTI-INFECTIVE DRUGS ADVISORY COMMITTEE.  THE JOINT 
COMMITTEE RECOMMENDED THAT FLUOROQUINOLONES FOR POULTRY BE 
APPROVED, BUT THAT USE OF THE DRUGS SHOULD BE LIMITED TO 
PRESCRIPTION ONLY, THAT NO EXTRA-LABEL USE SHOULD BE 
ALLOWED, AND THAT RESISTANCE SHOULD BE MONITORED AFTER THE 
PRODUCT WAS APPROVED.  APPROVAL OF BAYTRIL (TRADE NAME OF 
ONE PRODUCT) WAS LIMITED TO THERAPEUTIC USE, PRESCRIPTION 
ONLY, AND NO EXTRA-LABEL USE WAS ALLOWED. 
 
¶8.  FDA'S CVM CREATED A FLUOROQUINOLONE WORKING GROUP TO 
ADDRESS THE POINTS RAISED BY THE JOINT COMMITTEE. THE 
WORKING GROUP OFFERED SEVEN RECOMMENDATIONS, ALL OF WHICH 
                       UNCLASSIFIED 
 
PAGE 05        STATE   229699  041926Z 
WERE ACCEPTED BY CVM, AND SUBSEQUENTLY THE USE OF 
FLUOROQUINOLONES WAS APPROVED FOR POULTRY IN 1995 AND 1996. 
AS SUGGESTED IN THE RECOMMENDATIONS, THE SPONSORS AGREED TO 
PROVIDE BASELINE SUSCEPTIBILITY INFORMATION AND TO CONDUCT 
CONTINUING MONITORING OF TARGET ANIMAL PATHOGENS THROUGH 
THE POST-APPROVAL MONITORING PROGRAM.  HOWEVER, RESISTANCE 
DEVELOPED TO THE FLUOROQUINOLONES IN CAMPYLOBACTER, A MAJOR 
FOODBORNE PATHOGEN IN HUMANS.  IN NOVEMBER 1998, THE FDA 
ANNOUNCED DRAFT GUIDANCE FOR INDUSTRY ON THIS SUBJECT. 
FINALIZED IN DECEMBER 1999, THIS STATED THAT THE FDA 
BELIEVES IT IS NECESSARY TO CONSIDER THE POTENTIAL HUMAN 
HEALTH IMPACT, WHEN APPROVING SUCH DRUGS, OF THE MICROBIAL 
EFFECTS ASSOCIATED WITH ANTINICROBIAL "NEW ANIMAL DRUGS" 
INTENDED FOR USE IN FOOD-PRODUCING ANIMALS. 
 
¶9.  THE CENTER'S CONCLUSIONS ARE BASED ON DATA FROM THE 
NATIONAL ANTIMICROBIAL RESISTANCE MONITORING SYSTEM (A 
NATIONAL SURVEILLANCE PROGRAM OPERATED BY THE CENTER IN 
COOPERATION WITH THE CENTERS FOR DISEASE CONTROL AND 
PREVENTION AND THE U.S. DEPARTMENT OF AGRICULTURE), 
PUBLISHED LITERATURE, AND OTHER SOURCES.  THE DATA INDICATE 
THAT THE USE OF FLUOROQUINOLONES IN POULTRY IS A 
SIGNIFICANT CAUSE OF FLUOROQUINOLONE-RESISTANT 
CAMPYLOBACTER ON POULTRY CARCASSES, AND THEREFORE A 
SIGNIFICANT CAUSE OF FLUOROQUINOLONE-RESISTANT 
CAMPYLOBACTER INFECTIONS IN HUMANS. 
 
¶10.  ON OCTOBER 26, 2000, THE CVM ISSUED A "NOTICE OF 
OPPORTUNITY" FOR A HEARING ON A PROPOSAL TO WITHDRAW THE 
APPROVAL FOR USE OF ONE FLUOROQUINOLONE ANTIMICROBIAL IN 
POULTRY.  THE OFFICE OF THE FEDERAL REGISTER PUBLISHED THE 
                       UNCLASSIFIED 
 
PAGE 06        STATE   229699  041926Z 
NOTICE ON OCTOBER 31, 2000 (FEDERAL REGISTER VOLUME 65, 
NUMBER 211, 64954).  IF A COMPANY BELIEVES THAT IT SHOULD 
BE ABLE TO KEEP ITS PRODUCT ON THE MARKET, IT CAN SEEK A 
HEARING; THE REQUEST FOR A HEARING MUST BE MADE WITHIN 30 
DAYS AFTER THE NOTICE WAS PUBLISHED. TWO COMPANIES ARE 
CURRENTLY PRODUCING FLUOROQUINOLONE ANTIMICROBIALS FOR 
THERAPEUTIC USE IN POULTRY (SARAFLOXACIN AND ENROFLOXACIN). 
ONE COMPANY, WHICH PRODUCES SARAFLOXACIN, HAS REQUESTED A 
WITHDRAWAL OF ITS APPROVAL AND THEREFORE WILL NOT SEEK A 
HEARING.  THE OTHER COMPANY HAD NOT YET INDICATED IF IT 
WILL REMOVE ITS PRODUCT FROM THE MARKET.  THE FDA DOCUMENT 
IS AVAILABLE THROUGH FDA'S DOCKETS MANAGEMENT BRANCH, AT 
HTTP://WWW.FDA.GOV/OHRMS/DOCKETS/98FR/CV0076. PDF.  (NOTE: 
MORE INFORMATION ON FDA AUTHORITY TO REMOVE PRODUCTS FROM 
THE MARKET CAN BE FOUND AT: 
HTTP://WWW.FDA.GOV/FDAC/FEATURES/895_RECALLS. HTML). 
 
¶11.  CONSISTENT WITH ITS INTERNATIONAL OBLIGATIONS, THE 
UNITED STATES NOTIFIED FDA'S PROPOSAL TO THE WTO COMMITTEE 
ON SANITARY AND PHYOSANITARY MEASURES ON NOVEMBER 3. 
COMMENTS ARE DUE BY JANUARY 2, 2001. 
 
¶12. TALKING POINTS: 
 
--      THE U.S. FOOD AND DRUG ADMINISTRATION (FDA) HAS 
PROPOSED WITHDRAWING APPROVAL FOR THE USE OF ANTIBIOTICS 
(ANTIMICROBIALS), SPECIFICALLY FLUOROQUINOLONES, USED 
THERAPEUTICALLY IN POULTRY.  TWO COMPANIES ARE CURRENTLY 
PRODUCING FLUOROQUINOLONE ANTIMICROBIALS FOR THIS USE.  ONE 
COMPANY HAS AGREED TO WITHDRAW THE PRODUCT VOLUNTARILY FROM 
THE MARKET, WHILE THE OTHER COMPANY HAS YET TO ANNOUNCE ITS 
                       UNCLASSIFIED 
 
PAGE 07        STATE   229699  041926Z 
INTENTION. 
 
--      THE MAGNITUDE OF THE PUBLIC HEALTH RISK ASSOCIATED WITH 
ANTIMICROBIAL USE IN ANIMALS HAS BEEN DEBATED FOR OVER 
THIRTY YEARS. 
 
--      BASED UPON EMERGING SCIENTIFIC EVIDENCE THAT USES, 
INCLUDING THE THERAPEUTIC USE OF ANTIMICROBIALS IN FOOD- 
PRODUCING ANIMALS, MAY CAUSE BACTERIA TO DEVELOP RESISTANCE 
TO THE USE OF THE SAME OR SIMILAR ANTIBIOTICS IN HUMANS, 
THE FDA ANNOUNCED IN NOVEMBER 1998 DRAFT GUIDANCE FOR 
INDUSTRY ON THIS SUBJECT.  FINALIZED IN DECEMBER 1999, THIS 
STATED THAT FDA BELIEVES IT IS NECESSARY TO CONSIDER THE 
POTENTIAL HUMAN HEALTH IMPACT,  WHEN APPROVING SUCH DRUGS, 
OF THE MICROBIAL EFFECTS ASSOCIATED WITH ANTIMICROBIAL "NEW 
ANIMAL DRUGS" INTENDED FOR USE IN FOOD-PRODUCING ANIMALS. 
 
--      SINCE THE APPROVAL OF FLUOROQUINOLONES FOR THERAPEUTIC 
USE IN FOOD-PRODUCING ANIMALS IN 1995 AND 1996, 
SURVEILLANCE DATA HAVE IDENTIFIED A RELATIONSHIP BETWEEN 
THE APPROVAL OF FLUOROQUINOLONES FOR THERAPEUTIC USE IN 
POULTRY AND THE DEVELOPMENT OF FLUOROQUINOLONE RESISTANCE 
IN CAMPYLOBACTER IN ANIMALS AND HUMANS. 
 
--      FDA'S RISK ASSESSMENT WAS INTENDED TO ESTIMATE THE RISK 
TO HUMAN HEALTH FROM ANTIBIOTIC RESISTANT FOODBORNE 
PATHOGENS ASSOCIATED WITH THE DOMESTIC USE OF 
ANTIMICROBIALS IN FOOD PRODUCING ANIMALS.  SPECIFICALLY, A 
MATHEMATICAL MODEL WAS DERIVED TO RELATE THE PREVALENCE OF 
FLUOROQUINOLONE RESISTANT CAMPYLOBACTER INFECTIONS IN 
HUMANS ASSOCIATED WITH THE CONSUMPTION OF CHICKEN TO THE 
                       UNCLASSIFIED 
 
PAGE 08        STATE   229699  041926Z 
PREVALENCE OF FLUOROQUINOLONE RESISTANT CAMPYLOBACTER IN 
CHICKENS. 
 
--      FDA STATES IN THE NOTICE OF ITS PROPOSAL PUBLISHED 
OCTOBER 31, 2000 (FEDERAL REGISTER VOLUME 65, NUMBER 211, 
64954) THAT IT BELIEVES: 
 
¶1.  THE USE OF FLUOROQUINOLONES IN POULTRY CAUSES THE 
DEVELOPMENT OF FLUOROQUINOLONE- RESISTANT CAMPYLOBACTER, A 
PATHOGEN TO HUMANS, IN POULTRY; 
 
¶2.  THIS FLUOROQUINOLONE-RESISTANT CAMPYLOBACTER IS 
TRANSFERRED TO HUMANS AND IS A SIGNIFICANT CAUSE OF THE 
DEVELOPMENT OF FLUOROQUINOLONE-RESISTANT CAMPYLOBACTER 
INFECTIONS IN HUMANS; AND 
 
¶3.  FLUOROQUINOLONE-RESISTANT CAMPYLOBACTER INFECTIONS ARE 
A HAZARD TO HUMAN HEALTH. 
 
--      FOR MORE SPECIFIC INFORMATION ON THE RISK ASSESSMENT, 
IT CAN BE FOUND ON FDA'S WEB SITE AT: 
HTTP://WWW.FDA.GOV/CVM/FDA/MAPPGS/ANTITOC.HTM L 
 
--      THUS, FDA IS PROPOSING TO WITHDRAW THE APPROVAL FOR USE 
OF ENROFLOXACIN, ONE FLUOROQUINOLONE, IN POULTRY ON THE 
GROUNDS THAT NEW EVIDENCE SHOWS THE PRODUCT HAS NOT BEEN 
SHOWN TO BE SAFE. 
 
--      THE COMPANY PRODUCING ANOTHER FLUOROQUINOLONE FOR USE 
IN POULTRY, SARAFLOXACIN, PLANS TO WITHDRAW THE PRODUCT 
FROM THE MARKET. 
                       UNCLASSIFIED 
 
PAGE 09        STATE   229699  041926Z 
 
--      THE UNITED STATES NOTIFIED FDA'S PROPOSAL TO THE WTO 
COMMITTEE ON SANITARY AND PHYOSANITARY MEASURES ON NOVEMBER 
3, AS CALLED FOR UNDER INTERNATIONAL OBLIGATIONS.  COMMENTS 
ARE DUE BY JANUARY 2, 2001. 
 
(IF ASKED) 
 
--      IT IS UNCLEAR AT THIS STAGE IF THIS WILL AFFECT POULTRY 
PRODUCTS EXPORTED TO THE UNITED STATES.  THE FOOD SAFETY 
AND INSPECTION SERVICE IS EXAMINING THE FDA ACTION TO 
DETERMINE HOW POULTRY IMPORTS FROM COUNTRIES USING 
FLUOROQUINOLONES WILL BE HANDLED. 
ALBRIGHT 
 
                       UNCLASSIFIED