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##### Guidance for Industry

#### DISPUTE RESOLUTION PROCEDURES FOR SCIENCE-BASED DECISIONS ON PRODUCTS REGULATED BY THE CENTER FOR VETERINARY MEDICINE (CVM)

This guidance document describes the 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. Guide 1240.3130 (Center Appeals Procedure Guide) of the CVM Program
Policy and Procedures (P&P) Manual describes CVM's appeals procedure.
Because this Guide predates the Food and Drug Administration
Modernization Act (FDAMA), CVM is revising its procedures. This guidance
supersedes Guide 1240.3130, which has been deleted from the P&P Manual.

Comments and suggestions regarding this guidance should be sent to the
Division of Dockets Management (HFA-305), Food and Drug Administration,
5630 Fishers Lane, Room 1061, Rockville, MD 20852. Comments may also be
submitted electronically on the Internet at
<http://www.fda.gov/dockets/ecomments>. Once on this Internet site,
select \"\[03D-0167\]\[Dispute Resolution Procedures for Science-Based
Decisions on Products Regulated by the Center for Veterinary
Medicine\]\" and follow the directions. All written comments should be
identified with Docket No.03D-0167.

For questions regarding this guidance document, contact Marcia Larkins,
Center for Veterinary Medicine (HFV- 7), Food and Drug Administration,
7519 Standish Place, Rockville, MD 20855, 301-827-4535. E-mail:
<mlarkins@cvm.fda.gov>

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 <http://www.fda.gov/cvm>.

Paperwork Reduction Act (PRA) Public Burden Statement

According to the Paperwork Reduction Act of 1995, a collection of
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U.S. Department of Health and Human Services

Food and Drug Administration\
Center for Veterinary Medicine\
July, 2005

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#  DISPUTE RESOLUTION PROCEDURES FOR SCIENCE-BASED

### **DECISIONS ON PRODUCTS REGULATED BY CVM**

#######  I. INTRODUCTION

> **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.**
>
> 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.)

#######  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." 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**[.]{.smallcaps}** 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. Although 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, the procedure in
> 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 INAD (Investigational New Animal Drug), NADA (New Animal
> Drug Application), ANADA (Abbreviated New Animal Drug Application),
> IFA (Investigational Feed Additive), or FAP (Feed 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).
>
> 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 APPENDIX I, CVM Decision Review Process.
>
> A. [Review by the Supervisory Chain of Command]{.underline}
>
> 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 science-based
> 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]{.underline}

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:

> 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 the Veterinary
> Medicine Advisory Committee (VMAC) if the product is a drug or device
> as required by § 10.75(b)(2). Applicants of other products regulated
> by CVM may also request review by VMAC. 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 VMAC, the CVM
> Ombudsman should provide similar acknowledgement and forward the
> request to the CVM Director.
>
> [2. Deputy Center Director Ad Hoc Appeals Committee
> Procedure]{.underline}[:]{.smallcaps}
>
> 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]{.underline} [hoc]{.underline} 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 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.  [Veterinary Medicine Advisory Committee Procedure]{.underline}

> CVM has one standing advisory committee, the VMAC. The committee
> consists of 13 members representing a wide spectrum of disciplines and
> interests associated with veterinary medicine. The committee meets
> once or twice a year to give advice on broad scientific issues
> identified by CVM and the agency. 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 VMAC. A request
> for review by VMAC 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 to VMAC 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 VMAC to the CVM Ombudsman for
> consideration by the Center Director. CVM recommends that applicants
> filing a request for review by VMAC 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 VMAC
> 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.
>
> 2\. The Center should send a written response to the applicant\'s
> request for VMAC review within 30 calendar days of receiving the
> request. If the CVM Director denies a request for VMAC review, the
> reasons for the denial must be briefly set forth in writing to the
> applicant, if the product is a drug or device, as required by §10.75
> (b)(2). The reasons for the denial should also be briefly set forth in
> writing to applicants of other products regulated by CVM. 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 a VMAC review should be granted, but should work informally
> with the Center and the person denied VMAC review to develop a
> mutually acceptable approach, taking into account all relevant factors
> (63 FR 63978 at 63979).
>
> 3\. If the Center Director grants a request for VMAC review of the
> scientific controversy, VMAC 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 VMAC 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 VMAC 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 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 (see IV. A. above). 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. 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. 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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