Guidance for Industry 
 
 
Independent Consultants for 
Biotechnology Clinical Trial Protocols 
 
 
 
 
 
 
 
For questions on the content of this document contact Leonard Wilson, CBER at 301-827-0373 or 
Susan Johnson, CDER at 301-594-3937. 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research (CBER) 
Center for Drug Evaluation and Research (CDER) 
August 2004  Guidance for Industry 
 
Independent Consultants for 
Biotechnology Clinical Protocols  
 
 
 
 
 
Additional copies of this guidance are available from: 
Office of Communication, Training, and 
Manufacturers Assistance, HFM-40 
Center for Biologics Evaluation and Research 
Food and Drug Administration 
Suite 200N 
1401 Rockville Pike, Rockville, MD 20852-1448 
Internet: http://www.fda.gov/cber/guidelines.htm 
Phone:  800-835-4709 or 301-827-1800 
or 
Office of Training and Communication 
Division of Communications Management 
Drug Information Branch, HFD-210 
Center for Drug Evaluation and Research 
Food and Drug Administration 
5600 Fishers Lane, Rockville, MD 20857 
Phone:  301-827-4573 
Internet:  http://www.fda.gov/cder/guidance/index.htm 
 
 
 
  Contains Nonbinding Recommendations 
Table of Contents 
 
I.  WHY IS FDA ISSUING THIS GUIDANCE?.....................................................1 
II.  WHAT PRODUCTS ARE ELIGIBLE FOR THIS PROGRAM?.....................2 
III.  HOW DO YOU REQUEST THAT FDA ENGAGE AN INDEPENDENT 
CONSULTANT?...................................................................................................2 
IV.  DOES YOUR REQUEST AFFECT THE PDUFA MEETING 
MANAGEMENT GOALS?.................................................................................2 
V.  HOW MANY TIMES CAN YOU USE THIS PROGRAM DURING THE 
DEVELOPMENT OF YOUR PRODUCT?........................................................3 
VI.  CAN YOU RECOMMEND CONSULTANTS FOR THE FDA TO ENGAGE?
................................................................................................................................3 
VII.  WHAT IS THE STATUS AND ROLE OF THE CONSULTANT?...................3 
VIII.  WILL WE ALWAYS GRANT YOUR REQUEST?............................................4 
 
 
i  Contains Nonbinding Recommendations 
1
Guidance for Industry  
 
Independent Consultants for Biotechnology Clinical Trial 
Protocols  
 
 
This guidance document represents the agencys 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.  An alternative approach may be used if such approach satisfies the 
requirements of the applicable statutes and regulations. If you want to discuss an 
alternative approach, contact the appropriate FDA staff.  If you cannot identify the 
appropriate FDA staff, call the appropriate number listed on the title page of this 
guidance. 
 
I.  WHY IS FDA ISSUING THIS GUIDANCE?  
 
On June 12, 2002, the President signed the Public Health Security and Bioterrorism 
Preparedness and Response Act of 2002, which included the Prescription Drug User Fee 
Amendments of 2002 (PDUFA III).  Secretary Thompsons letter to Congress concerning 
PDUFA III included an addendum containing the performance goals and programs intended to 
facilitate the development and review of human drugs to which the Food and Drug 
Administration (FDA) had committed.  The letter and addendum can be found on the Internet at 
http://www.fda.gov/oc/pdufa/default.htm.  
One commitment was the establishment of a program that allows you, a sponsor of clinical trials 
for certain products, to request that we, FDA, engage an independent consultant to participate 
in the review of your protocol for a clinical study that is intended to serve as the primary basis of 
a claim of efficacy.  We are publishing this guidance to explain when and how you may take 
advantage of this program.  This guidance finalizes the draft guidance of the same title dated 
May 2003. 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe FDAs 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 FDAs guidances means that something is suggested or 
recommended, but not required.  
 
 
                                                 
1 This guidance has been prepared by the Center for Biologics Evaluation and Research (CBER) and the 
Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration. 
1  Contains Nonbinding Recommendations 
 
II.  WHAT PRODUCTS ARE ELIGIBLE FOR THIS PROGRAM?  
 
This program is available for a subset of products covered by PDUFA III.  Your product 
qualifies for this program if:  
 It is biotechnology-derived (for example, DNA plasmid products, synthetic peptides of 
fewer than 40 amino acids, monoclonal antibodies for in vivo use, and recombinant 
DNA-derived products),  
 It has the potential to represent a significant advance in the treatment, diagnosis, or 
prevention of a disease or condition, or to address an unmet medical need, and  
 The clinical study at issue is intended to serve as the primary basis of a claim of efficacy. 
 
III.  HOW DO YOU REQUEST THAT FDA ENGAGE AN INDEPENDENT 
CONSULTANT?  
 
We recommend that you submit a written request to us asking that we engage a consultant as 
part of your request for a formal meeting, (e.g., an End of Phase 2 meeting.)  You should clearly 
designate this as a Request for Appointment of Expert Consultant.  The request should include 
the information needed for the meeting as explained in FDAs Guidance for Industry: Formal 
Meetings With Sponsors and Applicants for PDUFA Products,2 dated February 2000, and 
the reasons that you believe an expert consultant should be engaged.  These reasons might 
include preliminary discussions with FDA that resulted in disagreement over the protocol or a 
novel or unorthodox approach to the clinical trial or its analysis.  
 
IV.  DOES YOUR REQUEST AFFECT THE PDUFA MEETING 
MANAGEMENT GOALS?  
 
Yes.  We will need time to select and screen the consultant for potential conflicts of interest and 
the consultant will need sufficient time to review the scientific issues involved.  Therefore, we will 
extend certain of the performance goals for scheduling and holding a meeting by 60 days.  We 
will notify you within 14 days of our intent to schedule your meeting and engage an independent 
consultant.  We will not be able to tell you when the meeting will be scheduled until we have 
engaged the consultant.  Similarly, if you wish the independent consultant to participate in other 
protocol assessment activities, such as a special protocol assessment and agreement, we will 
extend PDUFA performance goals related to those activities by sixty (60) days, to take into 
account the time necessary to select and screen the consultant.  The goal for any given meeting 
management activity will be extended by not more than 60 days.  It is our intention to schedule 
these activities as efficiently as possible. 
                                                 
2See www.fda.gov/cber/guidelines.htm. 
2  Contains Nonbinding Recommendations 
 
V.  HOW MANY TIMES CAN YOU USE THIS PROGRAM DURING THE 
DEVELOPMENT OF YOUR PRODUCT?  
 
We will engage an independent consultant under this program only once during the development 
of your product.  This restriction does not limit your ability to request that we take to an 
Advisory Committee an issue pertaining to the products marketing application review.  Nor 
does it limit our ability to take an issue to an Advisory Committee or otherwise to seek advice 
on an issue.  
 
VI.  CAN YOU RECOMMEND CONSULTANTS FOR THE FDA TO ENGAGE?  
 
You can submit a list of recommended consultants, their qualifications, and contact information 
for us to consider.  Prospective consultants will be screened for conflicts of interest.  We 
suggest that you do not recommend consultants:  
 Whom you know to have financial conflicts, 
 Who have been involved in the design or planning of the clinical trial, or  
 Whom you intend to ask to be an investigator.  
 
We may or may not select the consultant from your list of recommendations.  We will notify you 
of our selection prior to the formal meeting.  
 
VII.  WHAT IS THE STATUS AND ROLE OF THE CONSULTANT?  
 
Prospective consultants will be screened for potential conflicts of interest according to the 
criteria described in Policies and Procedures for Handling Conflicts of Interest with FDA 
Advisory Committee Members, Consultants, and Experts3 (FDA Waiver Criteria 2000) and be 
subject to confidentiality requirements.  The consultant we select may or may not already be a 
special government employee.  The consultant may:  
 Review the clinical protocol and appropriate background material,  
 Participate in our meeting with you, and 
 Provide us with advice on your clinical protocol and product development plan.  
 
We will remain responsible for making scientific and regulatory decisions regarding the clinical 
protocol, taking into account the consultants advice.  
 
                                                 
3 See http://www.fda.gov/oc/advisory/conflictofinterest/intro.html  
3  Contains Nonbinding Recommendations 
Following the completion of their service with respect to this program, consultants that we retain 
under contract are not restricted from other interactions with FDA.  These consultants will 
continue to be subject to the restrictions applicable to that position. (see footnote 3). 
 
VIII.  WILL WE ALWAYS GRANT YOUR REQUEST?  
 
We will grant your request unless we determine that engaging an expert consultant would not 
serve a useful purpose (e.g., it is clearly premature).   
 If we grant your request:  We will engage an independent consultant, of our choosing.   
 If we deny your request:  We will provide you with a written rationale for the denial 
within 14 days of receipt of your request for an expert consultant.   
 If you disagree with our rationale for refusing the request:  You may submit a request for 
formal dispute resolution.  
 
 
 
 
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