Guidance for Industry #79

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#79

Guidance for Industry
DISPUTE RESOLUTION PROCEDURES FOR SCIENCE-BASED
DECISIONS ON PRODUCTS REGULATED BY THE
CENTER FOR VETERINARY MEDICINE (CVM)
(Note: Due to the November 22, 2013 Federal Register notice (78 FR 69991) disbanding the
Veterinary Medicine Advisory Committee (VMAC), this guidance document is revised to reflect
updated procedures for handling a request for an internal review of scientific controversies
relating to a decision affecting animal drugs or other products that are regulated by CVM.)
Submit comments on this guidance at any time. Submit written comments to the Division of
Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane (Room
1061), Rockville, MD 20852. All comments should be identified with the Docket No. FDA2003-D-0307 (formerly docket number 2003D-0167). Submit electronic comments on the
guidance at http://www.regulations.gov.
For further information regarding this guidance document, contact Marcia Larkins, Center for
Veterinary Medicine (HFV-1), Food and Drug Administration, 7519 Standish Place, Rockville,
MD 20855, 240-276-9015. Email: [email protected].
Additional copies of this guidance document may be requested from the Communications Staff
(HFV-12), Center for Veterinary Medicine, Food and Drug Administration, 7519 Standish Place,
Rockville, MD 20855, and may be viewed on the Internet at either
http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/d
efault.htm or http://www.regulations.gov.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Veterinary Medicine
May 2014

Contains Nonbinding Recommendations

DISPUTE RESOLUTION PROCEDURES FOR SCIENCE-BASED
DECISIONS ON PRODUCTS REGULATED BY THE
CENTER FOR VETERINARY MEDICINE (CVM)
This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic. It
does not create or confer any rights for or on any person and does not operate to bind FDA or the public.
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes
and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for
implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate
number listed on the title page of this guidance.

I.

INTRODUCTION
This guidance document describes a recommended approach for resolution of disputes
relating to scientific controversies. A scientific controversy involves issues that arise within
the context of the Center’s regulation of a specific product and are related to matters of
technical expertise that require some specialized education, training, or experience in order to
be understood and resolved. The guidance document describes the dispute resolution
procedures that we recommend be followed by sponsors, applicants, and manufacturers when
requesting review of FDA decisions related to regulated products for animals. (Hereafter in
this document, the term applicant includes a sponsor, applicant, or manufacturer.)
FDA’s guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and
should be viewed only as recommendations, unless specific regulatory or statutory
requirements are cited. The use of the word should in Agency guidances means that
something is suggested or recommended, but not required.

II. BACKGROUND
On November 21, 1997, the President signed the Food and Drug Modernization Act of 1997
(FDAMA) into law (Public Law 105-115). Section 404 of FDAMA amends the Federal
Food, Drug, and Cosmetic Act (the act) by adding a provision (Section 562, 21 U.S.C. §
360bbb-1) for dispute resolution. If a procedure under which an applicant could request a
review of a scientific controversy related to human drugs, animal drugs, human biologics, or
devices did not already exist, either as a provision in the act or a regulation promulgated
under the act, FDAMA required FDA to establish a procedure by regulation through which
an applicant may request review of such scientific controversy, including a review by an
appropriate scientific advisory panel or advisory committee. Prior to FDAMA, a procedure
for review of such controversies was provided under §10.75 (21 CFR 10.75), Internal agency
review of decisions. § 10.75 provides for internal agency review of a decision through “the
established agency channels of supervision or review.”

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To implement Section 562, FDA amended 21 CFR Part 10 (Administrative Practices and
Procedures) to add the following:
A sponsor, applicant, or manufacturer of a drug or device regulated under the act or the Public Health
Service Act (42 U.S.C. 262), may request review of a scientific controversy by an appropriate scientific
advisory panel as described in section 505(n) of the act, or an advisory committee as described in section
515(g)(2)(B) of the act. The reason(s) for any denial of a request for such review shall be briefly set forth
in writing to the requester. Persons who receive a Center denial of their request under this section may
submit a request for review of the denial. The request should be sent to the Chief Mediator and
Ombudsman. (21 CFR 10.75(b)(2), 63 FR 63982, November 18, 1998)

There are significant differences in the statutory provisions that govern the regulation of the
various products regulated by FDA’s Centers, and similarly in the existing appeal and dispute
resolution mechanisms and approaches to advisory committee management. Therefore, FDA
did not include in § 10.75 specific procedures for requesting reviews of scientific
controversies, but has instead adopted a Center-based approach to resolving such disputes for
drugs or devices. Each affected Center is responsible for developing and administering its
own processes for handling requests for reviews of scientific controversies. This guidance
sets forth CVM’s recommended processes. Section 404 of FDAMA only required the
agency to establish dispute resolution procedures for scientific controversies involving drugs
and devices and § 10.75(b)(2) only applies to drugs and devices. With the exception of
Section IV.B. of this guidance, which describes the procedure for requesting advisory
committee review of a scientific dispute concerning a drug, the procedure in Section IV.A. of
this guidance may also be used by applicants for other products regulated by CVM.
III. SCIENTIFIC CONTROVERSIES ELIGIBLE FOR DISPUTE RESOLUTION
It is not CVM’s intent for applicants to use the dispute resolution procedure as their initial
response to “incomplete letters” that the Center sends to applicants when the Center needs
more information than contained in a submission in order to make a decision issued as a
result of Investigational New Animal Drug, New Animal Drug Application (NADA),
Abbreviated New Animal Drug Application, Investigational Food Additive, or Food Additive
Petition review. A scientific controversy may be considered eligible for dispute resolution
when there is an unresolved disagreement between applicants and Division Directors on
scientific decisions made by CVM including, but not limited to, the following examples:
A. CVM requests specific studies from an applicant in order to meet minimum pre-approval
data requirements (e.g., a request for more than one field trial, or a request for
antimicrobial resistance studies, or a request based on a recently implemented
regulation/guidance).
B. In compliance with the provisions of section 512(b)(3) (21 U.S.C. 360b(b)(3)) of the act,
CVM changes the data/protocol requirements that it had previously agreed to with the
applicant (e.g., based on new information discovered after a pre-submission conference).

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C. CVM determines that the information submitted by an applicant is inadequate (e.g.,
because the description of a particular aspect of a study in the protocol is inadequate, or
because a study is not acceptable for or applicable to a particular indication or assessment
of safety, or because the inferential value of an efficacy study is insufficient to support a
claim).
D. CVM and an applicant have different interpretations of the results/data from a study.
IV. DISPUTE RESOLUTION PROCEDURE
We recommend the applicant follow the dispute resolution procedure as explained below
when requesting review of a written scientific decision. The key features of the dispute
resolution procedure are also summarized in VII. CVM Decision Review Process.
A. Review by the Supervisory Chain of Command
The Code of Federal Regulations at § 10.75 states that any interested person may obtain
review of any agency decision by raising the matter through established agency channels
of supervision or review. CVM encourages applicants to begin the resolution of sciencebased disputes with discussions with the review team/group, including the Team Leader
or Division Director. The Center prefers that differences of opinion regarding science or
science-based policy be resolved between the review team/group and the applicant. If the
matter is not resolved by that method, we recommend that the applicant follow the
procedure below.
1. Office Level Appeals Procedure
a) When an applicant has a scientific disagreement with a written decision by FDA,
the applicant may submit to the Division Director, who is responsible for the
team/group/individual that communicated the decision, a request for review of
that decision. The initial appeal should identify the information in the
administrative file (the file) upon which the request is based. If the appeal
contains new information, not previously contained in the administrative file, the
matter will, in accordance with § 10.75(d), be returned to the appropriate lower
level in the agency for reevaluation based on the new information. A
reevaluation, based on the new information, is subject to the corresponding
review times provided by statute or regulation (e.g., 180 days for a NADA).
b) The Division Director should prepare a written response to the applicant's request
within 30 calendar days of receiving the request for review. The response should
include the reasoning/rationale for the decision.
c) If the applicant disagrees with the Division Director’s response, the applicant may
appeal in writing to the Office Director. The Office Director should prepare a
written response to the applicant’s appeal within 40 calendar days of receiving the
formal appeal. The response should include the reasoning/rationale for the
decision. The following options outlined below are some but not all of the
options available to the Office Director:
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i.

If the Office Director agrees with the applicant's position, the Office Director
should document his or her decision in writing and return the file to the
Division Director. The Division Director should expeditiously take
appropriate action to implement the Office Director’s decision and after
obtaining the Office Director’s concurrence on the response, communicate the
action (including the reasoning/rationale) to the applicant.

ii. If the Office Director disagrees in whole or in part with the applicant’s
position, he or she should document the decision in writing and return the file
to the Division Director. The Division Director should obtain the Office
Director’s concurrence on the response and notify the applicant of the
decision (including the reasoning/rationale for the decision) and of the
applicant’s right to have the issue forwarded to the CVM Ombudsman with a
request for either 1) consideration by a Deputy Center Director Ad Hoc
Appeals Committee (Ad Hoc Appeals Committee) or 2) review by an
advisory committee if the product is a drug as required by § 10.75(b)(2).
Applicants of other products regulated by CVM may only request review by
the Ad Hoc Appeals Committee. These two options for appeal are described
below. Either request should be sent in writing to the CVM Ombudsman with
courtesy copies to the appropriate Division and Office Directors. It is the
applicant’s responsibility to decide whether to continue to pursue the review
of a scientific decision. If the applicant requests consideration by the Ad Hoc
Appeals Committee, the CVM Ombudsman should provide written
acknowledgement to the applicant, within 14 days, and forward the request to
the CVM Deputy Director. If the applicant requests consideration by an
advisory committee, the CVM Ombudsman should provide similar
acknowledgement and forward the request to the CVM Director.
2. Deputy Center Director Ad Hoc Appeals Committee Procedure:
a) The Committee should generally consist of the CVM Deputy Director (or on rare
occasions, an alternate senior level Center manager), who acts as the Chair, and a
minimum of three members from the Center’s management and other experts
from the federal government appointed by the Chair. Selection of these
individuals should be on an ad hoc basis, depending on the issue involved. It is
expected that the Committee may also seek expert advice by consulting on an
individual, as-needed basis with others inside the Agency as well as outside the
Agency or the government, who possess expertise on the matter under
consideration.
b) The Chair should provide, in writing, an opportunity for the applicant to submit
written arguments and to meet with the Committee. If the applicant decides to
meet with the Committee, the applicant may bring as many consultants as the
applicant wishes. The meeting is to provide an opportunity for the full exchange
of information and views between the Committee and the applicant. The meeting
should be structured to allow for presentation by the applicant, input by the
appropriate CVM reviewing Division, and appropriate discussion. Finally, after
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the meeting, the Chair and the Committee members should deliberate without the
applicant, the applicant’s consultants, or personnel from the CVM reviewing
Division.
c) Following the deliberations, the Chair, with the advice of the Committee, should
make a decision on the issue and take appropriate action to implement the
decision. The Chair should provide the decision or a status report on the appeal to
the applicant in writing within 60 calendar days following the Committee
meeting. The response should include the reasoning/rationale for the decision.
d) If the Chair disagrees with the applicant’s position, and the applicant is not
satisfied with the decision, the applicant may appeal the Committee decision to
the Center Director by letter. The Center Director should respond in writing to
the applicant’s appeal within 40 calendar days of receipt. The response should
include the reasoning/rationale for the decision. If the Center Director also
disagrees with the applicant’s position, the applicant may submit an appeal by
letter to the Office of the Commissioner either directly or through the Office of
the FDA Ombudsman.
B. Advisory Committee Procedure
In cases involving broad scientific matters having a general impact on the veterinary drug
industry, and if time and budgetary constraints permit, the Center may refer a request for
the review of a scientific controversy to an advisory committee. A request for review by
an advisory committee from an applicant should relate to agency action on the applicant’s
own product.
1. Upon the applicant's request, the Center may refer a scientific controversy involving a
veterinary drug product to an advisory committee for review after the applicant has
requested review by the supervisory chain of command through the level of the Office
Director, as described in IV.A. The applicant may submit a written request for review
by an advisory committee to the CVM Ombudsman for consideration by the Center
Director. CVM recommends that applicants filing a request for review by an advisory
committee provide the CVM Ombudsman with a concise summary of the scientific
issue in dispute, including a summary of the particular FDA action or decision to which
the applicant objects, the results of all efforts that have been made to resolve the dispute
to date, and a clear articulated summary of the arguments and relevant data and
information. The information collected will form the basis for resolving the dispute
between the applicant and FDA. The Center Director should determine whether review
by an advisory committee is appropriate or, depending on the scientific issue involved,
whether the Ad Hoc Appeals Committee review procedure might provide a more
efficient means of resolving the scientific controversy.

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2. The Center should send a written response to the applicant's request for advisory
committee review within 30 calendar days of receiving the request. If the CVM
Director denies a request for advisory committee review, the reasons for the denial
must be briefly set forth in writing to the applicant, if the product is a drug, as required
by §10.75 (b)(2). The applicant may submit to the FDA Ombudsman a request for
review of the denial. The FDA Ombudsman should not make an independent
determination of whether an advisory committee review should be granted, but should
work informally with the Center and the person denied advisory committee review to
develop a mutually acceptable approach, taking into account all relevant factors (see 63
FR 63978).
3. If the Center Director grants a request for advisory committee review of the scientific
controversy, the reviewing advisory committee should make a recommendation to the
Center Director who should consider it in making a decision. While the purpose of an
advisory committee is to provide expert scientific advice and recommendations, the
conclusions of the advisory committee are not binding on the agency. The Center
Director should issue a written decision, including the reasoning/rationale for that
decision within 60 calendar days following the advisory committee meeting. If the
Center Director disagrees with the applicant’s position, and the applicant is not satisfied
with the decision, the applicant may choose to request further review by the Office of
the Commissioner.
Unless otherwise provided by law, the resolution of a scientific dispute by CVM is not final
agency action for purposes of judicial review.
V. THE ROLE OF THE OMBUDSMAN
CVM’s Ombudsman plays an important role in the dispute resolution process. This person is
committed to handling disputes in a neutral and confidential manner and to helping achieve
equitable solutions. The Ombudsman can help ensure that the process proceeds as smoothly
and fairly as possible.
A May 1, 1998, Presidential memorandum directs each federal agency to “promote greater
use of mediation, arbitration, early neutral evaluation, agency ombudsman and other ADR
[alternative dispute resolution] techniques” (Ref. 1). In addition to FDA’s formal processes,
several ombudsman offices, including one in CVM, have been established to facilitate the
resolution of disputes informally. FDA has established the Office of the Ombudsman within
the Commissioner’s Office to resolve inter-center disputes, hear appeals of decisions of the
Center Directors, and to resolve other disputes where the complainant has concerns about
raising the issue with a Center (see 63 FR 63978).
In a memo dated June 29, 1995, the Commissioner of Food and Drugs (the Commissioner)
reminded all FDA employees that companies are free to vigorously challenge agency
positions and requirements, and to freely voice their views (Ref. 2). By letter of the same
date, the Commissioner assured members of Congress that any act or threat of retaliation by
any FDA employee is totally unacceptable and will not be tolerated. Anyone who believes

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retaliation has occurred, or is likely to occur, is urged to contact the CVM Ombudsman,
Center management, or the Office of the FDA Ombudsman.
The function of the CVM Ombudsman is to help resolve disputes at the Center level,
typically in accordance with the procedures described in this guidance. The CVM
Ombudsman facilitates the resolution of disputes by operating in a neutral role, to help
achieve equitable solutions. The Ombudsman is also the Center’s point of contact for
information on the dispute resolution process (see 63 FR 63978) and is also responsible for
assuring the effective implementation of the process. An applicant may contact the
Ombudsman when the applicant does not know where or how to begin an appeal, little
progress is being made going up the chain of command, or a matter is not resolved in the
supervisory chain of command procedure (IV.A.). The Ombudsman helps to facilitate
administratively the formal appeals process above the Office level. The Ombudsman serves
as a neutral and may suggest alternatives to the procedures described in this guidance for
resolving disputes during the appeals process, subject to mutual agreement by the applicant
and CVM as described in the Administrative Dispute Resolution Act (ADRA) of 1996 (see 5
U.S.C. 571 (3) and (9), 573 (b)).
Additionally, anyone who believes that an employee has not followed proper good guidance
practices or has treated this or any guidance document as a binding document may also ask
the CVM Ombudsman for assistance. If the issue is not resolved at the Center level the
complainant may ask FDA’s Office of the Ombudsman to become involved (see 21 CFR
10.115(o)).
VI.

REFERENCES
1. President William J. Clinton. Memorandum for Heads of Executive Departments and
Agencies. Designation of Interagency Committees to Facilitate and Encourage Agency
Use of Alternate Means of Dispute Resolution and Negotiated Rulemaking. May 1,
1998.
2. Commissioner David A. Kessler. Memorandum to All FDA Employees. Allegations of
Retaliation. June 29, 1995.

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VII.

CVM Decision Review Process

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