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 O’Shea 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 

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Contains Nonbinding Recommendations 

Submission and Resolution of Formal Disputes Regarding the 

Timeliness of Premarket Review of a Combination Product 

topic. 

FDA or the public. 

This guidance represents the Food and Drug Administration's (FDA's) current thinking on this 

It does not create or confer any rights for or on any person and does not operate to bind 

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 OCP’s functions is to 

develop and implement policies and processes to streamline the review and regulation of drugdevice, 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 OCP’s functions and responsibilities is available at 

http://www.fda.gov/oc/combination/default.htm. Examples of ways OCP serves as a resource to sponsors 

and agency review staff are provided in the Office’s Report to Congress, posted at 

http://www.fda.gov/oc/combination/default.htm. 2

 OCP’s 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 applicant’s 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 May 

7, 2004, Federal Register (69 FR 25527), and is available at 

http://www.fda.gov/oc/combination/default.htm. 4

 The lead Center has responsibility for the premarket review and regulation of a combination product and 

will ordinarily be the sponsor’s primary contact point for issues surrounding the product’s review and 

regulation. 

5

 See http://www.fda.gov/oc/ombudsman/intercentersop.pdf for more information about how intercenter 

consultative reviews are requested, processed, and monitored. 

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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 PMA’s 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/oc/ombudsman/intercentersop.pdf for the agency’s Standard Operating Procedure on 

the Intercenter Consultative/Collaborative Review 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 noncombination products. Compliance with these time frames requires the Center to carefully observe queuing 

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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. 

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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 division’s 

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

 Please also see Guidance for Industry “Formal Dispute Resolution: Appeals above the Division Level,” 

at www.fda.gov/cber/gdlns.dispute.pdf. 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 http://www.fda.gov/cdrh/ombudsman/dispute.html. 

5 

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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. 

OCP’s 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; 

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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 applicant’s 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 division’s 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. 

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