Identifier
Created
Classification
Origin
00STATE229699
2000-12-04 19:24:00
UNCLASSIFIED
Secretary of State
Cable title:  

FDA PROPOSAL TO WITHDRAW APPROVAL FOR USE OF

Tags:  EAGR ETRD 
pdf how-to read a cable
UNCLASSIFIED PTO0648

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ORIGIN EB-00 

INFO LOG-00 AF-00 AGRE-00 AID-00 AIT-03 AMAD-00 AEX-01 
 AS-01 A-00 ACQ-00 CEA-01 CIAE-00 COME-00 CCOE-00 
 CTME-00 DODE-00 ITCE-00 ANHR-00 WHA-00 SRPP-00 EAP-00 
 EXME-00 EUR-00 E-00 UTED-00 FBO-01 VC-00 FRB-00 
 FSI-00 HHS-01 H-01 TEDE-00 INR-00 IO-00 ITC-01 
 L-00 MCO-01 MMP-00 AC-01 NEA-00 DCP-01 NSAE-00 
 NSCE-00 OES-01 OIG-03 OMB-01 OPIC-01 ACE-00 P-00 
 SP-00 IRM-00 SSO-00 SS-00 STR-00 TRSE-00 USIE-00 
 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

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SUBJECT: FDA PROPOSAL TO WITHDRAW APPROVAL FOR USE OF
ANTIMICROBIAL FLOUROQUINOLONE IN POULTRY

UNCLAS STATE 229699

SIPDIS

E.O. 12958: N/A
TAGS: EAGR ETRD
UNCLASSIFIED

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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
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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.

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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
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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
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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
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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
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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.
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-- 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