[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]
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