Contains Nonbinding Recommendations 
Guidance for Industry 

and FDA Staff 

Submission and Resolution of Formal Disputes Regarding the 
Timeliness of Premarket Review of a Combination Product  
Additional copies of this guidance are available at:  
http://www.fda.gov/oc/combination/default.htm 
or from: 
Office of Combination Products, HFG-3 
15800 Crabbs Branch Way, Suite 200 
Rockville, Maryland 20855 
Phone: 301-427-1934 
Fax: 301-427-1935 
e-mail: combination@fda.gov 
For questions regarding this document, contact Suzanne OShea at 301-827-1934 
or by email at:  combination@fda.gov 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Office of Combination Products  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
I. Introduction ................................................................................................................................. 1 

II. What is a premarket review timeliness dispute?........................................................................ 2 

III. What are the applicable time frames?....................................................................................... 3 

IV. When should a timeliness dispute resolution request be presented? ........................................ 4 

V. What is the process for presenting a timeliness dispute resolution request to OCP? ................ 5 

VI. What information should be included in a timeliness dispute resolution request ? ................. 6 

VII. How will OCP respond to a request for resolution of a timeliness dispute?........................... 7 

i  Contains Nonbinding Recommendations 
Submission and Resolution of Formal Disputes Regarding the 
Timeliness of Premarket Review of a Combination Product 

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
The Medical Device User Fee and Modernization Act of 2002 (MDUFMA) was enacted 
on October 26, 2002.  Among other things, this act created the Office of Combination Products 
(OCP) within the Office of the Commissioner of Food and Drugs.  One of OCPs functions is to 
develop and implement policies and processes to streamline the review and regulation of drug-
device, drug-biologic and device-biologic combination products as defined in 21 CFR 3.2(e).  For 
example, OCP is responsible for overseeing the timeliness of, and coordinating reviews of 
combination products when more than one agency Center is involved.  In addition, OCP is 
available as a resource to sponsors and agency reviewers at any time throughout the development 
of a combination product.1,2 
This guidance document provides information affecting a relatively narrow range of 
inquiries to OCP, i.e., for applicants wishing to present a formal dispute about the timeliness of 
review of a premarket application for a combination product. 
OCP does not have the authority to direct a reviewing division to take any particular 
action, but it is responsible for resolving disputes about the timeliness of premarket reviews of 
combination products:   
Any dispute regarding the timeliness of the premarket review of a combination 
product may be presented to the Office for resolution, unless the timeliness of the 
dispute is clearly premature.   
21 U.S.C.  353(g)(4)(E)(i). 
A combination product is assigned to an Agency center that will have primary 
jurisdiction for its regulation. Under section 503(g) of the Act, the assignment of a lead center 
is based upon a determination of the primary mode of action (PMOA) of the combination 
1 More information about OCPs functions and responsibilities is available at 
http://www.fda.gov/combination products. Examples of ways OCP serves as a resource to sponsors and 
agency review staff are provided in the Offices Report to Congress, posted at 
http://www.fda.gov/about-fda/reports/combination-products-performance-reports. 
2 OCPs contact information is provided later in this document.  Contains Nonbinding Recommendations 
product.3,4  For example, if the PMOA of a combination product is that of a biological product, 
then the combination product would be assigned to the Agency component responsible for 
premarket review of that biological product.  Depending upon the type of combination product, 
approval, clearance or licensure may be obtained through submission of a single marketing 
application, or through separate marketing applications for the individual constituent parts of the 
combination product.  
A center assigned primary jurisdiction for the regulation of a combination product 
frequently accomplishes its review in consultation or collaboration with another center.  Good 
communication between the lead and consulting centers, clear articulation of questions that arise 
throughout the review process, good review practices, appropriate supervisory review, effective 
pre-submission meetings and consultations, specified internal points of contact, and consultation 
milestones are all critical to ensuring a timely and effective premarket review process.   
FDA recognizes that timely premarket reviews also depend on timely and effective 
review consultations and collaborations between and among centers.  For this reason, the Agency 
has established a Standard Operating Procedure for the Intercenter Consultative/Collaborative 
Review Process to help ensure the timeliness and consistency of intercenter reviews.  For 
example, consultation time frames are established taking into account the time frame for Agency 
response to the regulatory submission.  Furthermore, OCP actively monitors the progress of 
consultative reviews to ensure their timely and effective completion.5 
Issues arising from the timeliness of internal consultations and collaborations are outside 
the scope of this guidance document.  This guidance document covers only disputes arising from 
the timeliness of the overall premarket review process for the marketing application. 
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. What is a premarket review timeliness dispute?
For the purpose of this guidance document, a timeliness dispute arises when FDA does 
not review and act on an applicants premarket submission within the applicable time frame, and 
the applicant presents the issue to OCP for resolution.  For example, if an applicable time frame 
states that a particular action is to be taken within 90 days, and the action is not taken by that 
time, the sponsor or applicant may present the issue to OCP for resolution.   
3 A proposed rule defining the primary mode of action of a combination product was published in the 
7, 2004, Federal Register (69 FR 25527), and is available at 
May 
http://www.federalregister.gov/documents/2004/05/07/04-10447/definition-ofprimary-mode-of-action-of 
a-combination product. 
4 The lead Center has responsibility for the premarket review and regulation of a combination product and 
will ordinarily be the sponsors primary contact point for issues surrounding the products review and 
regulation. 
5 See https://www.fda.gov/media/81927/download for more information about how intercenter 
consultative reviews are requested, processed, and monitored. 
2  Contains Nonbinding Recommendations 
III. What are the applicable time frames?
The Prescription Drug User Fee Act (PDUFA) and MDUFMA set performance goals for 
many types of drug, device, and biological product premarket applications.  (Goals pertaining to 
biologic license applications are contained in both PDUFA and MDUFMA.)  These goals reflect 
current expectations about the portion of premarket applications that will be reviewed within a 
specified time frame.  Performance goals apply to only a portion of all applications of a certain 
type;6 they do not require that every application be reviewed in accordance with the applicable 
time frame.  Nevertheless, because PDUFA and MDUFMA goals reflect current expected review 
time frames, OCP believes it is appropriate to use them as measures to evaluate whether 
timeliness dispute resolution requests are premature. 
Current PDUFA performance goals can be found at 
www.fda.gov/oc/pdufa/PDUFAIIIGoals.html. Current MDUFMA performance goals can be 
found at www.fda.gov/cdrh/mdufma/presentations/mdufma.html (Part III). 
In disputes related to combination product reviews, OCP expects to consider the time 
frames contained in PDUFA and MDUFMA performance goals in the following ways: 
1. When a combination product is to be reviewed under one premarket application, OCP
intends to consider the time frames associated with that type of premarket application.
For example, if a combination product consisting of drug and device constituent parts is
to be reviewed only under a new drug application, then OCP would consider the
performance goals associated with new drug applications.7 
2. When a combination product is reviewed under two premarket applications, OCP intends
to consider the time frames associated with each type of premarket application.  For
example, if a combination product consisting of drug and device constituent parts is to be
reviewed under both a device application and a new drug application, then OCP would
consider the time frames associated with device applications to that portion of the review
covered by the device application.  Similarly, OCP would consider the time frames
associated with new drug applications to that portion of the review covered by the new
drug application.8 
6 For example, under current PDUFA performance goals, FDA is to review and act on 90 percent of 
priority original NDA and BLA submissions within 6 months.  Similarly, under MDUFMA performance 
goals, in 2005, FDA is to issue 75 percent of its major deficiency letters on PMAs within 150 days. 
7  Similarly, if a combination product consisting of drug and device constituent parts were to be reviewed 
by CDRH solely under a device application with a consult by CDER, then the performance goals associated 
with that type of device application would apply. Furthermore, CDER would provide its review of the drug 
constituent part to CDRH within the device application time frames. See 
http://www.fda.gov/media/81927/download for the agencys Staff Manual Guide on the Intercenter Consult 
Request Process, which provides that consultative review deadlines take into account the time frame for 
agency response to the regulatory application. 
8  FDA believes it is not feasible to apply the shorter time frame to both types of marketing applications 
when two types of applications are submitted. PDUFA and MDUFMA provide time frames for all 
applications reviewed by a Center, whether the applications cover combination products or non-
combination products.  Compliance with these time frames requires the Center to carefully observe 
queuing 
3  Contains Nonbinding Recommendations 
3. OCP intends to consider time frames to be applicable to combination products even if the
applicant does not pay a user fee; for example, when the sponsor is granted a waiver of an
applicable user fee.
Some types of submissions are not covered by user fee time frames.  For example, there
are no user fee time frames for applications covering allergenic extracts, blood and blood 
components for transfusion, Investigational New Drug applications (21 CFR Part 312) or 
Investigational Device Exemption applications (21 CFR Part 812); nor is there a user fee time 
frame covering the review of humanitarian use devices (21 CFR Part 814, Subpart H).  In a 
situation where there is no applicable user fee time frame, OCP intends to consider any relevant 
time frame identified in an applicable statute or regulation to determine whether a timeliness 
dispute resolution request is premature.  In situations where there is no applicable statute or 
regulation, sponsors are encouraged to contact OCP to discuss the issue and determine the best 
way to proceed.   
IV. When should a timeliness dispute resolution request be presented?
The purpose of a timeliness dispute resolution request is to ensure timely completion of 
the relevant review, rather than to impose any sanction on the reviewing Center.  In keeping with 
this perspective, OCP recommends that dispute resolution requests be presented after the relevant 
deadline has been missed, and before the reviewing Center has completed its premarket review.  
For example, if a relevant performance goal states that a particular action is to be taken within 90 
days, and the Center completes the review on day 93, a timeliness dispute resolution request 
presented on day 95 would do nothing to further the goal of obtaining a timely review. 
As noted above, when a combination product is reviewed under two marketing 
applications, OCP would consider the time frames associated with each type of application.  
Applicants with combination products reviewed under two types of applications may submit 
dispute resolution requests for one of the applications, even if the time frame for the second 
application has not yet passed.  For example, if a combination product is being reviewed by both 
CDER and CDRH under drug and device applications respectively, and CDRH fails to meet the 
relevant MDUFMA time frame, but the PDUFA time frame for action on the drug application has 
not yet occurred, a timeliness dispute resolution request covering the device application would 
not be premature once the MDUFMA time frame has not been met.  A request related to the 
device application would be timely even though the PDUFA time frame had not passed for the 
drug application. 
On occasion, a reviewing division may inform an applicant in advance that an applicable 
time frame will not be met.  In that case, a request for a timeliness dispute resolution presented 
regimens, and to closely manage reviewers time.  When two applications are submitted for the review of a 
combination product, OCP will consider the time frames associated with each type of application because 
to apply only the shorter time frame (e.g. to apply 510(k) time frames to an NDA) would disrupt the 
queuing of all other applications and possibly prevent reviewers from meeting the time frames for other 
applications covering non-combination products. 
4  Contains Nonbinding Recommendations 
before the time stated in the relevant performance goal has passed would further the goal of 
obtaining a timely review.  OCP recommends that applicants base such a timeliness dispute 
resolution request on a letter, facsimile, FDA meeting minutes, or some other statement from 
FDA that a time frame will not be met.   
This guidance document does not cover planning discussions or, in the absence of clear 
notification from the reviewing division, prospective concerns about a reviewing divisions 
ability to meet a time frame in the future.  OCP recommends that resolution of such issues be 
facilitated through informal procedures outside the scope of this guidance. 
V. What is the process for presenting a timeliness dispute resolution request to OCP?
We recommend that sponsors and applicants try to resolve disputes with the lead 
division, office and center before contacting OCP.  If an applicant believes that a date for action 
on an application has passed without action, or if the reviewing division in the lead center informs 
the applicant that an applicable time frame will not be met, OCP recommends that the applicant 
first discuss the status of the review with the reviewing division and/or the Office to which the 
reviewing division reports within the lead Center.9 The Center ombudsmen identified below are 
also available to assist you:   
CBER: 
Sheryl Lard-Whiteford, Ph.D. 

Ombudsman 

Center for Biologics Evaluation and Research 
1401 Rockville Pike (HFM  4) 

Rockville, MD 20857 

301-827-5413
CDRH: 
Les Weinstein, Esq. 

Ombudsman 

Center for Devices and Radiological Health 
9200 Corporate Blvd. (HFZ-5) 

Rockville, MD 20850 

301-827-7991
9  Please also see Guidance for Industry Formal Dispute Resolution:  Appeals above the Division Level, 
at https://www.fda.gov/media/85613/download. This guidance document sets forth procedures adopted by 
CBER and CDER to resolve scientific and procedural disputes above the division level. Information about 
dispute resolution guidance issued by CDRH is available at https://www.fda.gov/about-fda/cdrh-
ombudsman/resolution-differences-opinion. 
5  Contains Nonbinding Recommendations 
CDER: 
Warren Rumble 

Ombudsman 

5515 Security Lane (HFD-006) 
Suite 500 

Rockville, MD 20852 

301-594-5480
If the reviewing division or appropriate Office within the lead center does not provide the 
applicant with a satisfactory response, it would be appropriate to direct the timeliness dispute to 
OCP. 
OCP encourages timeliness disputes to be presented by letter, fax or e-mail. 
OCPs contact information is:  
Office of Combination Products 

15800 Crabbs Branch Way, Suite 200 
HFG  3 

Rockville, MD 20855 

Telephone: (301) 427-1934

Fax: (301) 427-1935 

Email: combination@fda.gov

VI. What information should be included in a timeliness dispute resolution request ?
A timeliness dispute resolution request should include the following information:
1. Contact information for the applicant;
2. The name of the product, and information about why the product is a combination
product;
3. The Request for Designation number if the product went through the Request for
Designation process;
4. The FDA Center and reviewing division that is responsible for the premarket review;
5. The application number assigned by the reviewing Center or division;
6. The type of application;
7. Any relevant user fee performance goal;
8. The date the applicant believes the action was due;
9. The name and telephone number of the FDA contact person for the application;
6  Contains Nonbinding Recommendations 
10. A summary of the information provided by the reviewing division in the lead center
regarding the timeliness of the review; and
11. A summary of the applicants perspective on issues or barriers to progress affecting the
timeliness of the premarket review process.
VII. How will OCP respond to a request for resolution of a timeliness dispute?
Upon receipt and review of a timeliness dispute resolution request, OCP expects to place 
a telephone call to the Director of the reviewing division in the lead center, and to the appropriate 
Center Ombudsman.  When appropriate, OCP will convene a meeting with the reviewing 
division, the Center Ombudsman, and/or with the applicant.  The purpose of the telephone call 
and/or meeting will be to determine: 
1. whether the Division Director and the Center Ombudsman agree that the
relevant user fee time frame has not been met;
2. the current status of the review;
3. issues that need to be resolved before the review can be completed; and
4. what OCP can do to facilitate the completion of a timely review, and if
necessary and feasible, a plan for the completion of the review, including a
target date for completion of the review.
OCP will next place a telephone call to the applicant to discuss the current status of the 
review, and when appropriate and feasible, the review divisions plan for completing the review.  
OCP intends to provide this information to the applicant within 10 working days after the 
timeliness dispute is presented to OCP.  
If the reviewing division fails to meet the new target date for completion of the review, 
the applicant should advise OCP if further follow-up is requested.  OCP will then follow up with 
the reviewing division on behalf of the applicant. 
7