[Federal Register Volume 65, Number 166 (Friday, August 25, 2000)]
[Proposed Rules]
[Pages 51782-51787]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-21692]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 514

[Docket No. 00N-1399]


Presubmission Conferences

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
its new animal drug regulations to describe the procedures to be 
followed for requesting, conducting, and documenting presubmission 
conferences. Under the Federal Food, Drug, and Cosmetic Act (the act), 
as amended by the Animal Drug Availability Act of 1996 (ADAA), any 
person intending to file a new animal drug application (NADA) or 
supplemental (NADA) or to investigate a new animal drug is entitled to 
one or more conferences with FDA to reach an agreement establishing a 
submission or investigational requirement. This proposed regulation 
describes how a person would request a presubmission conference and 
describes the procedures for the conduct of the presubmission 
conference.

DATES: Submit written comments on the proposed rule by November 8, 
2000. Submit written comments on the information collection provisions 
by September 25, 2000.

ADDRESSES: Submit written comments on the proposed rule to the Dockets 
Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers 
Lane, rm. 1061, Rockville, MD 20852. Submit written comments on the 
information collection requirements to the Office of Information and 
Regulatory Affairs, Office of Management and Budget, New Executive 
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn: 
Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: Gail L. Schmerfeld, Center for 
Veterinary Medicine (HFV-100), Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855, 301-594-1620.

SUPPLEMENTARY INFORMATION:

I. Background

    The ADAA (Public Law 104-250) was enacted on October 9, 1996. 
Section 512(b)(3) of the act (21 U.S.C. 360b(b)(3)), as amended by 
section 2(d) of the ADAA, provides that any person intending to file an 
NADA or supplemental NADA or to investigate a new animal drug is 
entitled to one or more conferences with FDA prior to such submission 
or during the investigation of a new animal drug. The purpose of such a 
conference is to reach an agreement establishing a submission or 
investigational requirement. A decision establishing a submission or 
investigational requirement can be changed only if: (1) FDA and the 
potential applicant mutually agree to modify the requirement, or (2) 
FDA by written order determines that a substantiated scientific 
requirement essential to the determination of safety or effectiveness 
of the animal drug involved has appeared after the conference. If FDA 
determines that more than one field study is required to establish by 
substantial evidence that an intended use of a new animal drug is 
effective, FDA will provide written scientific justification for that 
decision within 25 calendar days of the conference. While section 
512(b)(3) of the act does not entitle persons who intend to file an 
abbreviated new animal drug application (ANADA) to request a 
presubmission conference, such potential applicants are entitled to 
request presubmission conferences under this proposed rule.
    Although the ADAA added a statutory entitlement to a presubmission 
conference, FDA's Center for Veterinary Medicine (CVM) had already been 
encouraging sponsors of NADA's to participate in conferences with FDA 
to discuss in detail what studies are necessary to demonstrate the 
safety and effectiveness of a new animal drug. In its experience with 
these presubmission conferences, FDA found that, as a result of this 
direct and detailed communication during the development and review of 
new animal drugs, fewer unusable studies were conducted and there were 
fewer delays in the review process. Consequently, companies saved 
resources and the marketing of new animal drugs became more 
expeditious. FDA's success with the use of presubmission conferences to 
establish submission requirements for new animal drugs was also 
reflected in its commitment to implement broad use of presubmission 
conferences as part of the President's reinventing government 
initiatives (e.g., ``Reinventing the Regulation of Animal Drugs,'' May 
1996). The ADAA codifies FDA's use of presubmission conferences.

II. Description of Proposed Rule

    The regulations being proposed by FDA would establish the 
procedures for requesting, conducting, and documenting presubmission 
conferences. Presubmission conferences will continue to be like those 
that were held between applicants and FDA prior to the enactment of the 
ADAA. The purpose of presubmission conferences is to allow FDA and a 
potential applicant, i.e., a person intending to investigate a new 
animal drug or to file an NADA, supplemental NADA, or ANADA, to discuss 
and reach agreement regarding a submission or investigational 
requirement. A submission or investigational requirement includes, 
among other things, identification of the number and types of studies 
that are necessary to demonstrate the safety and effectiveness of a new 
animal drug for the intended uses and conditions of use prescribed, 
recommended, or suggested in the proposed labeling for the new animal 
drug. Presubmission conferences give FDA and a potential applicant a 
means to identify the least burdensome appropriate requirements that 
have a reasonable likelihood of resulting in approval.
    Meetings other than presubmission conferences may be necessary 
during the development and review of new animal drugs. Meetings in 
which the focus is other than to establish the safety and effectiveness 
data requirements for new animal drugs (e.g., meetings relating to 
administrative processes, protocol development, or label development) 
are not specifically covered by this proposed rule.

A. Definitions (Proposed Sec. 514.3)

    Proposed Sec. 514.3 defines the terms ``potential applicant,'' 
``presubmission conference,'' and ``presubmission conference 
agreement'' as those terms are used in 21 CFR part 514. ``Potential 
applicant'' means any person intending to investigate a new animal 
drug, file an NADA or supplement, or file an ANADA. One or more 
``presubmission conferences'' may be needed to establish agreement 
regarding part or all of a submission or investigational requirement. 
Agreement on a submission or investigational requirement reached by a 
potential applicant and FDA in a presubmission conference(s) will be 
recorded in the ``presubmission conference agreement'' section of the 
memorandum of conference prepared by FDA and will be

[[Page 51783]]

binding upon both FDA and the potential applicant.

B. Presubmission Conferences (Proposed Sec. 514.4)

    Proposed Sec. 514.4 describes procedures for requesting, 
conducting, and documenting a presubmission conference.
1. Requesting a Presubmission Conference
    Under the proposed rule, a potential applicant could request a 
presubmission conference any time prior to filing an NADA, supplemental 
NADA, or ANADA, including before a potential applicant submits a notice 
of claimed investigational exemption for a new animal drug. In order to 
request a presubmission conference, a potential applicant would be 
required to submit to FDA a letter requesting a presubmission 
conference. FDA would have to receive the request for a presubmission 
conference at least 30 calendar days prior to the requested conference 
date. The potential applicant would identify the request as a request 
for a presubmission conference and would have to include a proposed 
agenda and a list of the expected attendees. FDA would, to the extent 
agency resources permit, make every effort to schedule the 
presubmission conference at the earliest time agreeable to both FDA and 
the potential applicant. In order to ensure a productive exchange of 
views and efficient use of FDA resources, a potential applicant would 
also be required to forward to FDA, at least 30 calendar days in 
advance of the scheduled conference date the following: A copy of any 
materials to be presented at the conference; a list of proposed 
indications for the new animal drug or, if available, a copy of the 
proposed labeling; and a copy of any relevant background material that 
provides the scientific rationale to support the potential applicant's 
position on an issue to be discussed during the conference. If such 
materials are not provided or are not sufficient to provide the basis 
for a meaningful discussion, FDA may elect to postpone the meeting 
until it receives sufficient materials.
2. Conducting a Presubmission Conference
    A presubmission conference (or series of such conferences) would be 
directed primarily at establishing agreement between FDA and the 
potential applicant regarding part or all of a submission or 
investigational requirement. The potential applicant and FDA could each 
bring consultants to the presubmission conference.
3. Documenting a Presubmission Conference
    Under the proposed rule, FDA would prepare a memorandum of 
conference summarizing the substance of each presubmission conference, 
including all key discussion points, decisions, recommendations, 
agreements reached regarding all or part of a submission or 
investigational requirement, disagreements, and action items. That 
portion of the memorandum of conference that documents any agreements 
reached regarding all or part of a submission or investigational 
requirement would be the ``presubmission conference agreement'' and 
would be denoted as such by a heading as such. FDA would provide a copy 
of this memorandum to the potential applicant and give the potential 
applicant 30 calendar days to request changes to or seek clarification 
of the substance of the memorandum. The potential applicant could elect 
to have the copy of the memorandum provided by mail, by facsimile, and/
or by some electronic media. For purposes of calculating the 30 days, 
FDA would use the date the memorandum is mailed, facsimiled, or 
electronically transmitted from the Documents Control Unit, whichever 
is earlier. If a potential applicant were to request changes or 
clarification, such a request should be directed to the appropriate 
Division Director in CVM. A copy of FDA's original memorandum of 
conference and a copy of the memorandum with changes or clarification, 
as appropriate, would be made part of the administrative file. If a 
memorandum is silent on an issue, including one that was discussed 
during the conference or addressed by materials provided by the 
potential applicant for the conference, such silence cannot be 
construed as agreement between FDA and the potential applicant on the 
issue. A copy of the final memorandum would be provided to the 
potential applicant. FDA would file in the administrative record, but 
not review or consider binding in any way, a memorandum of conference 
prepared by a potential applicant.
    If FDA determines that more than one field study is necessary to 
demonstrate effectiveness, in accordance with section 512(b)(3) of the 
act, it would provide, either separately or as part of a memorandum of 
conference, written scientific justification for its decision within 25 
calendar days of the date such decision is made. FDA would not, 
however, provide such written scientific justification if the potential 
applicant voluntarily proposes to conduct more than one field study but 
FDA does not believe multiple studies are necessary. The potential 
applicant's proposal to conduct more than one field study would be 
documented in the memorandum of conference.
    One study can be a study at a single location or a study in which 
data are collected from multiple locations. Results obtained in a 
single location study may be dependent on site specific factors (e.g., 
disease definition, concomitant treatment, diet, management practices, 
climate, field conditions, etc.). In such cases, the results, although 
significant with respect to that site, may not permit inferences to be 
made to the intended target animal population. If FDA requires one 
field study to be conducted at multiple locations, at the request of 
the potential applicant, FDA would provide verbal or written 
justification for requiring multiple locations. Written justification 
could be provided separately or as part of a memorandum of conference. 
FDA intends to issue guidance to industry regarding the use of field 
studies to provide substantial evidence of effectiveness.
    Presubmission conference agreements would generally include 
timeframes for completion. The agreements would assume that the 
potential applicant would use due diligence to complete the drug 
development process within those timeframes and FDA would use due 
diligence to complete its reviews within reasonable timeframes. If a 
potential applicant were to fail to meet the terms of an agreement, the 
agreement would have no precedential value for subsequent agreements 
relating to the same new animal drug because standards may change over 
time. Similarly, agreements relating to one new animal drug would have 
no precedential value with respect to other new animal drugs because 
requirements may vary from drug to drug or intended use to intended 
use.
    Agreements reached through a presubmission conference could be 
modified under the limited circumstances described in proposed 
Sec. 514.4(g). Proposed Sec. 514.4(h) describes how a potential 
applicant may breach an agreement. The act provides that FDA breaches 
an agreement if it unilaterally modifies the agreement without a 
written order determining that a substantiated scientific requirement 
essential to the determination of safety or effectiveness appeared 
after the conference. Proposed Sec. 514.4(i) describes procedures for 
resolving disputes that may arise between a

[[Page 51784]]

potential applicant and FDA during the presubmission conference 
process.
    FDA encourages potential applicants to meet with FDA at any time to 
discuss submission requirements.

III. Environmental Impact

    The agency has determined under 21 CFR 25.30(h) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

IV. Analysis of Impacts

    FDA has examined the impact of the proposed rule under Executive 
Order 12866 and under Regulatory Flexibility Act (5 U.S.C. 601-612). 
Executive Order 12866 directs agencies to assess all costs and benefits 
of available regulatory alternatives and, when regulation is necessary, 
to select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). The agency believes that 
this proposed rule is consistent with the regulatory philosophy and 
principles identified in the Executive Order. In addition, the proposed 
rule is not a significant regulatory action as defined by the Executive 
Order and so is not subject to review under the Executive Order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities unless the rule is not expected to have a significant 
economic impact on a substantial number of small entities. As this 
proposed rule will not impose significant new costs on any firms, under 
the Regulatory Flexibility Act (5 U.S.C. 605(b)), the agency certifies 
that the proposed rule will not have a significant impact on a 
substantial number of small entities. Therefore, under the Regulatory 
Flexibility Act, no further analysis is required.
    Under section 512(b)(3) of the act, as amended by the ADAA, any 
person intending to file an NADA or supplemental NADA or to investigate 
a new animal drug is entitled to one or more conferences prior to such 
submission to reach an agreement establishing a submission or 
investigational requirement. The purpose of a presubmission conference 
is to allow a potential applicant and FDA to discuss and to reach 
agreement regarding a submission or investigational requirement, 
including the number and types of studies that are necessary to 
demonstrate that a new animal drug is safe and effective for its 
intended uses.
    Prior to the enactment of the ADAA, CVM had already been 
encouraging sponsors of NADA's to participate in conferences with FDA 
to discuss in detail what studies are necessary to demonstrate the 
safety and effectiveness of the particular new animal drug being 
investigated. FDA found that, as a result of this direct communication 
during the development and review of new animal drugs, both the drug 
development and review processes became more efficient. This proposed 
rule would implement the statutory entitlement to a presubmission 
conference and, thus, ensure that this benefit will continue where 
applicants request a presubmission conference. To the extent that this 
proposed rule would educate those in the industry that were not 
familiar with presubmission conferences, there will be further benefits 
as additional potential applicants realize efficiencies gained in the 
animal drug development and application process if they request a 
presubmission conference.
    FDA is not able to make a precise estimate of the savings that 
industry has realized through the presubmission conferences up to this 
point, or of any increase in the number of presubmission conferences 
that may be requested as a result of this rule. There are many factors 
that determine the type and number of studies necessary to demonstrate 
the safety and effectiveness of new animal drugs. This proposed rule 
seeks to secure an avenue of communication between the agency and 
potential applicants through which both can agree on the studies needed 
for a certain drug, thereby reducing unnecessary studies and review 
periods.
    It is possible, however, to forecast a range of savings that may be 
expected to result from any decrease in approval time resulting from 
the use of a presubmission conference. For this purpose, FDA estimated 
a straight-line increase of a prospective drug's sales revenues from 
the application's approval up to $5 million in the 10th year and then 
decreasing again to zero in the 20th year. Since many drugs attain 
sales much greater than $5 million, the agency estimate results in a 
rather conservative benefit. Assuming a pretax profit of 20 percent of 
sales revenue, FDA estimates the present value of the profits from a 1- 
to 6-month decrease in approval time at $20,000 to $120,000 using a 7 
percent discount rate. Research costs saved by the firm from not 
conducting unnecessary studies would be added to this amount. 
Regardless of the exact reduction in the drug review period, since the 
presubmission conferences are voluntary, applicants would only be 
expected to request a conference if they expected the net benefit of 
the conference to be positive. The proposed rule would not impose any 
mandatory compliance costs.

V. Unfunded Mandates Reform Act of 1995

    Section 202(a) of the Unfunded Mandates Reform Act of 1995 (Public 
Law 104-4) requires that agencies prepare a written statement of 
anticipated costs and benefits before proposing any rule that may 
result in an expenditure by State, local, and tribal governments, in 
the aggregate, or by the private sector, of $100 million in any one 
year (adjusted annually for inflation).
    The Unfunded Mandates Reform Act does not require FDA to prepare a 
statement of costs and benefits for the proposed rule, because the 
proposed rule is not expected to result in any 1-year expenditure that 
would exceed $100 million adjusted for inflation. The current 
inflation-adjusted statutory threshold is $110 million.

VI. Federalism

    FDA has analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. FDA has determined that 
the proposed rule does not contain policies that have substantial 
direct effects on the States, on the relationship between the National 
Government and the States, or on the distribution of power and 
responsibilities among the various levels of government. Accordingly, 
the agency has concluded that the rule does not contain policies that 
have federalism implications as defined in the order and, consequently, 
a federalism summary impact statement is not required.

VII. Paperwork Reduction Act of 1995

    This proposed rule contains information collection provisions that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-
3520). A description of these provisions is given below with an 
estimate of the annual reporting burden. Included in the estimate is 
the time for reviewing instructions, searching existing data sources, 
gathering and maintaining the data needed, and completing and reviewing 
each collection of information.

[[Page 51785]]

    With respect to the following collection of information, FDA 
invites comments on: (1) Whether the proposed collection of information 
is necessary for the proper performance of FDA's functions, including 
whether the information will have practical utility; (2) the accuracy 
of FDA's estimate of the burden of the proposed collection of 
information, including the validity of the methodology and assumptions 
used; (3) ways to enhance the quality, utility, and clarity of the 
information to be collected; and (4) ways to minimize the burden of the 
collection of information on respondents, including through the use of 
automated collection techniques when appropriate, and other forms of 
information technology.
    Title: Presubmission Conferences
    Description: The proposed regulation is intended to implement 
section 512(b)(3) of the act which entitles any person intending to 
file an NADA or supplemental NADA or to investigate a new animal drug 
to request one or more conferences with FDA to reach an agreement 
establishing a submission or investigational requirement. Prior to the 
enactment of section 512(b)(3) of the act, FDA encouraged sponsors to 
meet with FDA to discuss the number and types of studies necessary to 
demonstrate that a new animal drug is safe and effective. FDA found 
that these informal presubmission conferences increased the efficiency 
of the drug development and drug review processes. FDA is publishing 
this proposed regulation to describe how to request, conduct, and 
document a presubmission conference.
    Proposed section 514.4(b) describes the information that must be 
included in a letter submitted by a potential applicant requesting a 
presubmission conference, including a proposed agenda and a list of 
expected participants. Proposed section 514.4(d) lists the information 
that must be provided by the potential applicant to FDA prior to a 
presubmission conference. This information includes a copy of any 
materials to be presented at the conference, a list of proposed 
indications or a copy of the proposed labeling for the product under 
consideration, and any background material that provides an adequate 
scientific rationale to support the potential applicant's position on 
issues listed on the proposed agenda for the conference. Proposed 
section 514.4(f) discusses the content of the memorandum of meeting 
that will be prepared by FDA and proposes to allow the potential 
applicant to seek clarification or correction of the memorandum.
    Table 1 of this document provides, by relevant section, the 
estimated burden of requesting, preparing for, and participating in 
presubmission conferences. The numbers in the chart are based on recent 
consultation with several of the major research and development firms 
that are responsible for the development of new animal drugs. While FDA 
estimates that the proposed regulation would increase the annual 
paperwork burden associated with the submission of NADA's, supplemental 
NADA's, and abbreviated NADA's, and requests for guidance on 
investigational requirements, FDA believes this increase will be offset 
by the resulting efficiencies (e.g., eliminating the conduct of studies 
that are not needed to demonstrate safety and effectiveness, decreasing 
the requests from reviewers for additional or clarifying information 
during the review process).
    Description of Respondents: Potential applicants

                                 Table 1.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
                                                      Annual
         21 CFR Section               No. of       Frequency per   Total Annual      Hours per      Total Hours
                                    Respondents      Response        Responses       Response
----------------------------------------------------------------------------------------------------------------
514.4(b)                              190               1             190               7           1,330
514.4(d)                              190               1             190             123          23,370
514.4(f)                              190               1             190              16           3,040
Total                                                                                             27,740
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital cost or operating and maintenance costs associated with this collection of information.

    In compliance with section 3507(d) of the PRA, the agency has 
submitted the information collection provisions of this proposed rule 
to OMB for review. Interested persons may submit to OMB (address above) 
written comments regarding the information collection by September 25, 
2000.

Lists of Subjects in 21 CFR Part 514

    Administrative practice and procedure, Animal drugs, Confidential 
business information, Reporting and recordkeeping requirements.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR part 514 be amended as follows:

PART 514--NEW ANIMAL DRUG APPLICATIONS

    1. The authority citation for 21 CFR part 514 continues to read as 
follows:

    Authority: 21 U.S.C. 351, 352, 360b, 371, 379e, 381.
    2. Section 514.2 is added to subpart A to read as follows:


Sec. 514.2  Definitions.

    (a) Potential applicant means any person intending to:
    (1) Investigate a new animal drug under section 512(j) of the 
Federal Food, Drug, and Cosmetic Act (the act),
    (2) File a new animal drug application (NADA) or supplemental NADA 
under 512(b)(1) of the act, or
    (3) File an abbreviated new animal drug application (ANADA) under 
section 512(b)(2) of the act.
    (b) Presubmission conference means one or more conferences between 
a potential applicant and FDA, requested by the potential applicant, to 
reach a binding agreement establishing a submission or investigational 
requirement.
    (c) Presubmission conference agreement means that section of the 
memorandum of conference headed ``Presubmission Conference Agreement'' 
that records any agreement on the submission or investigational 
requirement reached by a potential applicant and FDA during the 
presubmission conference. The presubmission conference agreement will 
be binding on the potential applicant and FDA unless it is modified as 
described in Sec. 514.5(g).
    3. Section 514.5 is added to subpart A to read as follows:


Sec. 514.5  Presubmission conferences.

    (a) General. Presubmission conferences provide a forum for a

[[Page 51786]]

potential applicant and FDA to reach agreement regarding the overall 
plan for conducting investigations of new animal drugs or obtaining 
approval of a new animal drug, including to discuss what studies are 
required to support approval of a new animal drug application (NADA), a 
supplemental NADA, or an abbreviated new animal drug application 
(ANADA), and to discuss the objectives and general design of particular 
studies. Presubmission conferences, as a project management tool, can 
enhance the animal drug development and evaluation process. The general 
principle underlying the conduct of any such conference is that there 
must be candid, full, and open communication about scientific or 
medical issues pertaining to the safety and effectiveness of an 
investigational new animal drug.
    (b) Requesting a presubmission conference. A potential applicant is 
entitled to one or more conferences prior to the submission of an NADA, 
supplemental NADA, or an ANADA to reach an agreement establishing part 
or all of a submission or investigational requirement. Potential 
applicants must request a presubmission conference by submitting their 
request to the appropriate Center for Veterinary Medicine (CVM) 
Division Director in a signed letter. The letter must include a 
proposed agenda that clearly outlines the scope, purpose, and 
objectives of the presubmission conference and must list the names and 
positions of the representatives who are expected to attend the 
presubmission conference on behalf of the potential applicant.
    (c) Timing. A potential applicant may request one or more 
presubmission conferences at any time prior to the filing of a NADA, 
supplemental NADA, or an ANADA. A request for a presubmission 
conference must be received by FDA at least 30 calendar days in advance 
of the requested conference date. FDA will schedule the presubmission 
conference at a time agreeable to both FDA and the potential applicant.
    (d) Advance information. The potential applicant must provide to 
FDA, at least 30 calendar days in advance of a scheduled presubmission 
conference, a copy of any materials to be presented at the conference, 
a list of proposed indications or a copy of the proposed labeling for 
the product under consideration, and any background material that 
provides an adequate scientific rationale to support the potential 
applicant's position on issues listed on the proposed agenda for the 
conference. If the materials are not provided or are not sufficient to 
provide the basis for meaningful discussion, FDA may elect to postpone 
the meeting until sufficient materials are provided to FDA.
    (e) Conduct of a presubmission conference. The potential applicant 
and FDA may each bring consultants to the presubmission conference. The 
presubmission conference(s) will be directed primarily at establishing 
agreement between FDA and the potential applicant regarding a 
submission or investigational requirement. The submission or 
investigational requirement will include the number and types of 
studies that are necessary to demonstrate the safety and effectiveness 
of a new animal drug for the intended uses and conditions of use 
prescribed, recommended, or suggested in the proposed labeling for the 
new animal drug.
    (f) Documentation of a presubmission conference--(1) Memorandum of 
conference. FDA will prepare a memorandum of each conference 
summarizing the substance of the conference: Key discussion points, 
decisions, recommendations, agreements reached regarding all or part of 
a submission or investigational requirement, disagreements, and action 
items. That portion of the memorandum of conference that documents any 
agreements reached regarding all or part of a submission or 
investigational requirement will be included under the heading 
``Presubmission Conference Agreement.'' FDA will provide a copy of the 
memorandum to the potential applicant for review. The potential 
applicant will have 30 calendar days from the date a copy of the final 
draft of the memorandum is provided to the applicant to request changes 
to or clarification of the substance of the memorandum. For purposes of 
calculating the 30 days, FDA will use the date the memorandum is 
mailed, facsimiled, or electronically transmitted to the potential 
applicant from the Document Control Unit, whichever is earlier. If a 
potential applicant requests changes or clarification, such request 
should be directed to the appropriate CVM Division Director. A copy of 
FDA's original memorandum of conference and a copy of the memorandum 
with changes or clarification, as appropriate, will be made part of the 
administrative file. If a memorandum is silent on an issue, including 
one that was discussed in the conference or addressed by materials 
provided for the conference, such silence cannot be construed as 
agreement between FDA and the potential applicant on the issue. FDA 
will provide the potential applicant with a copy of the final 
memorandum.
    (2) Field studies. If FDA requires more than one field study to 
establish by substantial evidence that the new animal drug is effective 
for its intended uses under the conditions of use prescribed, 
recommended, or suggested in the proposed labeling, FDA will provide 
written scientific justification for requiring more than one field 
study. Such justification must be provided no later than 25 calendar 
days after the date of the conference at which the requirement for more 
than one field study is established. If FDA does not believe more than 
one field study is required but the potential applicant voluntarily 
proposes to conduct more than one field study, FDA will not provide 
such written justification. If FDA requires one field study to be 
conducted at multiple locations, FDA will, at the request of the 
potential applicant, provide written or verbal justification for 
requiring multiple locations.
    (g) Modification of presubmission conference agreements. An 
agreement made under a presubmission conference requested under section 
512(b)(3) of the Federal Food, Drug, and Cosmetic Act and documented in 
a memorandum of conference is binding on the potential applicant and 
FDA and may only be modified if:
    (1) FDA and the potential applicant mutually agree to modify, in 
part or in whole, the agreement and such modification is documented and 
provided to the potential applicant as described in paragraph (f)(1) of 
this section; or
    (2) FDA by written order determines that a substantiated scientific 
requirement essential to the determination of safety or effectiveness 
of the new animal drug appeared after the conference.
    (h) When the terms of a presubmission conference agreement are no 
longer binding. (1) A presubmission conference agreement will no longer 
be binding if:
    (i) The potential applicant makes to FDA, before, during, or after 
the presubmission conference, any untrue statement of material fact; or
    (ii) The potential applicant fails to follow any term of the 
agreement; and
    (2) A presubmission conference agreement may no longer be binding 
if the potential applicant submits false or misleading data relating to 
a new animal drug to FDA.
    (i) Dispute resolution. FDA is committed to resolving differences 
between a potential applicant and FDA reviewing divisions with respect 
to requirements for the investigation of new animal drugs and for 
NADA's,

[[Page 51787]]

supplemental NADA's, and ANADA's as quickly and amicably as possible 
through a cooperative exchange of information and views. When 
administrative or procedural disputes arise, a potential applicant 
should first attempt to resolve the matter within the appropriate 
review division beginning with the individual(s) most directly assigned 
to review of the application or investigational exemption. If the 
dispute cannot be resolved after such attempts, the dispute shall be 
evaluated and administered in accordance with applicable regulations 
(21 CFR 10.75). Dispute resolution procedures may be further explained 
by guidance available from CVM.

    Dated: August 17, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-21692 Filed 8-24-00; 8:45 am]
BILLING CODE 4160-01-F