[Federal Register Volume 67, Number 34 (Wednesday, February 20, 2002)]
[Notices]
[Pages 7700-7701]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-4082]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00N-1571]


Enrofloxacin for Poultry; Notice of Hearing

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing a hearing 
on a proposal to withdraw approval of a new animal drug application 
(NADA). In the Federal Register of October 31, 2000 (65 FR 64954), the 
Director of FDA's Center for Veterinary Medicine (CVM) issued a notice 
of opportunity for a hearing (NOOH) proposing to withdraw approval of 
NADA 140-828 for enrofloxacin (Baytril 3.23% Concentrate Antimicrobial 
Solution). Bayer Corp., the sponsor of the new animal drug, responded 
by filing a request for a hearing on November 29, 2000.
    This notice of hearing (NOH) provides factual and legal information 
concerning CVM's proposal to withdraw the NADA and identifies the 
factual issues that will be the subject of the evidentiary hearing.

DATES: A prehearing conference will be held on April 8, 2002, beginning 
at 10 a.m. Any person wishing to participate in this hearing shall 
submit a written notice of participation by March 22, 2002. Disclosure 
of data and information as required by part 12 (21 CFR part 12) must be 
made by April 22, 2002.

ADDRESSES: The prehearing conference will be held in conference room. 
F, 5600 Fishers Lane, Rockville, MD 20857. You must submit written 
notices of participation and disclosure of data and information to 
Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. All submissions must 
reference docket number 00N-1571.

FOR FURTHER INFORMATION CONTACT: Robin Thomas Johnson, Office of Policy 
(HF-26), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 
20857, 301-827-3480.

SUPPLEMENTARY INFORMATION:

I. Background

    Enrofloxacin belongs to the class of antimicrobial drugs called 
fluoroquinolones. Fluoroquinolones are used in humans and animals for 
therapeutic purposes. Bayer Corp., P.O. Box 390, Shawnee Mission, KS 
66201-0390, sponsor of NADA 140-828 for enrofloxacin (also known under 
Bayer's product name ``Baytril'') was approved for use in poultry on 
October 4, 1996, and published on November 5, 1996 (61 FR 56892). The 
new animal drug is indicated for the control, in chickens, of mortality 
associated with Escherichia coli (E. coli) susceptible to enrofloxacin. 
It is indicated for the control, in turkeys, of mortality associated 
with E. coli and Pasteurella multocida (P. multocida) susceptible to 
enrofloxacin.

II. Statutory Grounds Proposed for Withdrawal of the NADA for 
Enrofloxacin

    In the NOOH published on October 31, 2000 (as revised on January 
22, 2001), CVM proposed to withdraw approval of NADA 140-828 for use in 
poultry under section 512(e)(1)(B) of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S. C. 360b(e)(1)(B)) . Section 
512(e)(1)(B) states:
    (e)(1) The Secretary shall, after due notice and opportunity for 
hearing to the applicant, issue an order withdrawing approval of an 
application filed pursuant to subsection (b) with respect to any new 
animal drug if the Secretary finds --
* * * * *
    (B) that new evidence not contained in such application or not 
available to the Secretary until after such application was 
approved, or tests by new methods, or tests by methods not deemed 
reasonably applicable when such application was approved, evaluated 
together with the evidence available to the Secretary when the 
application was approved, shows that such drug is not shown to be 
safe for use under the conditions of use upon the basis of which the 
application was approved or that subparagraph (I) of paragraph (1) 
of subsection (d) applies to such drug.
    CVM must provide a reasonable basis from which serious questions 
about the ultimate safety of the drug may be inferred. ```Serious 
questions' can be raised where the evidence is not conclusive, but 
merely suggestive of an adverse effect.'' (See 44 FR 54852 at 54861, 
September 21, l979 (Commissioner's DES Decision.) Once CVM provides a 
basis for questioning the safety of enrofloxacin, the sponsor will have 
the ultimate burden of showing the drug's safety. See Rhone-Poulenc, 
Inc., Hess & Clark Div. v. FDA, 636 F.2d 750 (D.C. Cir. 1980); 21 CFR 
12.87(d); 44 FR 54852 at 54861, September 21, l979 (Commissioner's DES 
Decision); 49 FR 34965, September 4, 1984 (Notice of Hearing for 
Nitrofurazone); and, 56 FR 41902, August 23, 1991 (Commissioner's 
Nitrofurans Decision).

III. Summary of the Evidence

    In accordance with FDA's procedural regulations (Sec. 12.85) CVM 
has placed on file with the Dockets Management Branch (address above) 
copies of all documents in the CVM Director's files containing factual 
information relating to the issues involved in the hearing, and a 
narrative statement summarizing the evidence CVM plans to introduce at 
the hearing. For the benefit of those who are unable to inspect those 
documents, the information placed on file by CVM is summarized below.
    The primary factual issues at the hearing will be whether there is 
a reasonable basis from which serious questions about the safety of 
enrofloxacin use in poultry may be inferred, and, if so, whether the 
use of enrofloxacin under the approved conditions of use in poultry has 
been shown to be safe. This action is based on CVM's determination that 
the use of fluoroquinolones in poultry causes the development of 
fluoroquinolone-resistant Campylobacter spp., a human pathogen, in 
poultry; that this fluoroquinolone-resistant Campylobacter spp. is 
transferred to humans and is a significant cause of the development of 
fluoroquinolone-resistant Campylobacter infections in humans; and 
thatfluoroquinolone-resistant Campylobacter infections in humans are a 
human health hazard. (See 65 FR 64954.)
    CVM has concluded, based on data from surveillance programs, 
published literature, and other sources, 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. This conclusion is supported by data establishing a temporal 
association between approval of fluoroquinolones for use in poultry and 
an increase influoroquinolone-resistant Campylobacter infections in 
humans; by a comparison of fluoroquinolone use in poultry with other 
possible cause of fluoroquinolone-resistant human infections; and a 
risk assessment that determined that in 1999, a mean estimate of 9,261 
persons infected with campylobacteriosis and prescribed a

[[Page 7701]]

fluoroquinolone in the United States would have had a fluoroquinolone-
resistant illness due to the use of fluoroquinolones in chickens.
    CVM believes that such people are likely to have had prolonged 
illnesses or complications. CVM concluded that development of 
resistance to fluorquinolones among Campylobacter has important 
consequences for human health since patients with severe enteric 
disease such as campylobacteriosis are usually treated empirically. CVM 
believes that Campylobacter resistance presents a dilemma for the 
physician. If fluoroquinolone treatment is given based on symptoms, and 
the patient is infected with fluoroquinolone-resistant Campylobacter 
spp., there is a risk that the treatment will not be effective, or will 
be less effective, and valuable time will be lost. If treatment is 
delayed until the causative organism and susceptibility are confirmed 
by a medical laboratory, again valuable time will be lost. In these 
situations, the disease may be prolonged or result in complications, 
especially in vulnerable patients with underlying health problems.

IV. Conclusion

    Upon review of Bayer Corp.'s response to the NOOH, the Acting 
Principal Deputy Commissioner concludes that a hearing is appropriate 
with respect to CVM's proposal to withdraw approval of the NADA for 
enrofloxacin. The issue at the hearing will be as follows:
    Whether new evidence shows that enrofloxacin is not now shown to be 
safe for use under the conditions of use upon the basis of which the 
application was approved. This issue includes:
    A. Whether there is a reasonable basis from which serious questions 
about the safety of enrofloxacin use in poultry may be inferred, such 
as:
    1. Whether enrofloxacin use in poultry acts as a selection 
pressure, resulting in the emergence and dissemination of 
fluoroquinolone-resistant Campylobacter spp. In poultry?
    2. Whether fluoroquinolone-resistant Campylobacter spp. in poultry 
are transferred to humans and whether they contribute to 
fluoroquinolone-resistant Campylobacter infections in humans?
    3. Whether fluoroquinolone-resistant Campylobacter infections in 
humans have the potential to adversely affect human health?
    B. Whether the use of enrofloxacin under the approved conditions of 
use in poultry has been shown to be safe?
    The hearing on these issues will take place in FDA conference room 
F. Administrative Law Judge Daniel J. Davidson will preside. Parties to 
the hearing will be CVM and Bayer Corp., the sponsor of the NADA for 
enrofloxacin. Any other interested person may participate in the 
hearing and be accorded the rights granted to participants by FDA 
regulations. Participants are required to assume the obligations of 
participation as set forth in FDA regulations (see part 12). Written 
notices of participation shall be filed with the Dockets Management 
Branch no later than March 22, 2002 (see Sec. 12.45). A notice of 
participation shall be identified with the docket number found in 
brackets in the heading of this document and clearly labeled 
``Enrofloxacin Hearing.''
    A prehearing conference will be held on April 8, 2002. All 
participants are required both to attend the prehearing conference and 
to be prepared to comply with Sec. 12.92, which sets forth the 
procedure and matters to be considered at such conference.
    As discussed above, CVM has filed with the Dockets Management 
Branch a narrative statement setting forth its position on the hearing 
issues and a detailed factual description of the evidentiary background 
upon which it intends to rely at the hearing. CVM has also filed with 
the Dockets Management Branch the other documents required by 
Sec. 12.85, including copies of the relevant portions of NADA, 
published studies, and other data, bearing on the question of whether 
enrofloxacin has been shown to be safe for use under the conditions of 
use upon the basis of which the application was approved. Interested 
persons may obtain a copy of the narrative statement from the Dockets 
Management Branch. With the exception of any data withheld from public 
disclosure under the provisions of 21 CFR 10.20(j), 21 U.S.C. 331(j), 
or 18 U.S.C. 1905, the data described above may also be examined at the 
Dockets Management Branch between 9 a.m. to 4 p.m., Monday through 
Friday. Bayer Corp. shall submit all the written data and information 
requiredby Sec. 12.85 by April 22, 2002. All other participants shall 
submit all written data and information required bySec. 12.85 by April 
22, 2002. Any request to extend the period for submission of the 
required materials or for a postponement of the scheduled prehearing 
conference shall be addressed to the Administrative Law Judge.
    The prehearing conference and the hearing will be open to the 
public. Any participants may appear in person, or by or with counsel, 
or with other qualified representatives, and may be heard on relevant 
matters.
    Because this is a public hearing, it is subject to our guideline 
concerning the policy and procedures for electronic media coverage of 
public agency administrative proceedings. This guideline was published 
in the Federal Register on April 13, 1984 (49 FR 14723). These 
procedures are primarily intended to expedite media access to our 
public proceedings, including formal evidentiary hearings conducted 
under part 12 of the agency's regulations. Under this guideline, 
representatives of the electronic media may be permitted, subject to 
certain limitations, to videotape, film, or otherwise record our public 
administrative proceedings, including the testimony of witnesses in the 
proceedings. Accordingly, the parties and nonparty participants to this 
hearing, and all other interested persons, are directed to the 
guideline, for a more complete explanation of the guideline's effect on 
this hearing.
    This notice is issued under section 512 of the Federal Food, Drug, 
and Cosmetic Act (21 U.S.C. 360b), and under authority delegated to the 
Commissioner of Food and Drugs (21 CFR 5.10).

    Dated: February 13, 2002.
Bernard A. Schwetz,
Acting Principal Deputy Commissioner.
[FR Doc. 02-4082 Filed 2-15-02; 8:45 am]
BILLING CODE 4160-01-S