FY 2019

PERFORMANCE REPORT

TO CONGRESS

for the

Office of 

Combination Products

as required by the

Medical Device User Fee and

Modernization Act of 2002
Commissioner’s Report

I am pleased to submit the fiscal year 2019 annual performance report to Congress for the 

Office of Combination Products (OCP) in the U.S. Food and Drug Administration (FDA). This 

report includes data from the 16

th full year since OCP was established, as mandated by the 

Medical Device User Fee and Modernization Act of 2002 (P.L. 107-250), enacted on October 

26, 2002.

Combination products are therapeutic and diagnostic products that combine a drug, device, 

and/or biological product. Technological advances continue to merge product types and blur 

the historical lines of separation among FDA’s human medical product Centers, which include 

the Center for Biologics Evaluation and Research, the Center for Drug Evaluation and 

Research, and the Center for Devices and Radiological Health. Combination products involve 

constituent parts that would usually be regulated under different types of regulatory authorities

and frequently by different FDA Centers, which can raise regulatory, policy, and review 

management challenges. Differences relating to the regulatory pathways and the 

considerations for each type of constituent part (i.e., drug, device, and/or biological product) can 

impact the regulatory processes for all aspects of combination product development and 

management, including preclinical testing, clinical investigation, marketing applications, 

manufacturing and quality control, adverse event reporting, promotion and advertising, user 

fees, and postapproval modifications.

OCP continues to enhance the efficiency, consistency, transparency, and predictability of the 

process for assigning combination products to the appropriate lead Center and for the

regulatory process. In this regard, OCP acts to facilitate interactions between industry and FDA 

to clearly delineate regulatory pathways, monitor and adjust processes to ensure a timely and 

effective premarket review, and help ensure a consistent and appropriate postmarket regulation 

of combination products. In addition to combination products, OCP has classification and 

assignment responsibilities for non-combination drug, device, and biological products.

Combination products are likely to become more complicated as new technologies emerge and 

existing technologies mature. OCP will continue to focus on the most important issues relating 

to the regulation of combination products. OCP is committed to actively assisting industry and 

FDA reviewers in understanding the complexities of this regulatory area. 

FDA looks forward to ensuring success in meeting the unique challenges in the review and 

regulation of combination products.

Stephen M. Hahn, M.D.

Commissioner Food and Drugs
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Executive Summary

The U.S. Food and Drug Administration (FDA or the Agency) established the Office of 

Combination Products (OCP) on December 24, 2002, as required by the Medical Device User 

Fee and Modernization Act of 2002 (P.L. 107-250). The statutory mission of OCP is to ensure 

the prompt assignment of combination products (for drug-device, biologic-device, drug-biologic, 

or drug-device-biologic products) to FDA’s Centers; the timely, effective, and aligned premarket 

review of applications for these products; and the consistent and appropriate postmarket 

regulation of these products subject to the relevant statutory requirements to the extent 

permitted by law. 

This report presents OCP’s annual performance report to Congress and covers activities and 

accomplishments during fiscal year (FY) 2019 (i.e., October 1, 2018 to September 30, 2019). 

OCP’s activities and performance for FY 2019 that are highlighted in this report include: 

1. Prompt Assignment of Combination Products. In FY 2019, OCP continued to clarify 

the classification and jurisdictional (i.e., Center) assignment of medical products and to 

provide prompt Request for Designation (RFD) decisions. OCP issued seven

combination product and six non-combination RFD decisions, with every classification 

and/or assignment decision meeting the 60-day statutory decision time requirement. 

Refer to Tables 1-3 for trending data from FY 2014 through FY 2019. OCP also 

provided timely classification and jurisdictional feedback for 83 separate Pre-Request for 

Designation submissions. OCP issued 94 percent of Pre-RFD by OCP’s internally 

established 60-day goal date, a slight decrease from 98% in 2018 and 96% in 2017. For 

trending data from FY 2017 through FY 2019, view Table 6.

2. Timely and Effective Combination Product Review. In FY 2019, OCP received 144 

requests for product-specific assistance, the responses to which contributed to ensuring 

the timely and effective review of combination products. There was a 59 percent 

decrease from the number of requests received in FY 2019 compared to the 5-year 

average (i.e., from FY 2014 to FY 2018). Other OCP activities relating to premarket 

review included chairing and/or participating in a number of inter-Center working groups 

to examine complex regulatory issues, clarifying regulatory standards, addressing 

challenging categories of products, updating the premarket review process, and 

addressing developmental considerations for combination products.

a. FDA received 518 original premarket applications for combination products in FY 

2019. This reflects a 33 percent increase from the 390 original premarket applications 

reported in FY 2018.1 Inter-Center consulting reviews for combination products 

decreased to 1,328 for FY 2019 from 1,445 in FY 2018. Examples of combination 

product types can be found on the Combination Products web site.2 

 

1 FY 2018 numbers have been changed to reflect updates to the data presented in the FY 2018 OCP 

performance report. The updated data for FY 2018 are located in Appendix A.

2 Available at www.fda.gov/CombinationProducts/default.htm.
3. Consistent and Appropriate Postmarket Regulation. In FY 2019, OCP provided 

clarification and support for 62 separate postmarket matters. OCP continued to chair 

FDA working groups to address current good manufacturing practices and postmarketing 

safety reporting (PMSR) requirements for combination products. Notably, FDA published 

a final guidance in July 20193to help implement its December 2016 final rule on PMSR 

for combination products.4 In addition, OCP worked with other Agency components to 

enhance training, databases, and resources to support postmarket inspectional and 

related manufacturing compliance oversight and to support implementation of the 2016 

PMSR rule in anticipation of compliance enforcement dates in July 2020 and 2021.5 OCP 

also continued to work with the medical product Centers on registration and listing issues, 

postmarket manufacturing compliance, and other postmarket regulatory issues pertaining 

to specific combination products.

4. Procedural and Policy Activities and Accomplishments. In FY 2019, the cross-cutting 

decisional Combination Products Policy Council consisting of senior leaders from all three 

human medical product Centers, the Office of Clinical Policy and Programs, and OCP

continued to provide direction regarding complex policy and procedural questions for 

combination products, other medical products intended for combined use, and the 

classification and assignment of medical products. Topics addressed included 

implementation of section 3038 of the 21st Century Cures Act, human factors, the interCenter consult process, the availability of premarket pathways for combination products, 

the inter-component coordination on combination product policy activities, and regulatory 

considerations for cross-labeled and other separately distributed medical products 

intended for combined use. Among other efforts, in FY 2019, OCP worked with the 

human medical product Centers to issue one proposed rule, five final guidances, and six 

draft guidances relating to combination products and combined use of medical products. 

OCP also continued to conduct external outreach activities through a variety of 

educational and informational presentations to national and international audiences, 

presenting at eleven conferences during the fiscal year. These activities were intended to 

foster greater efficiency, consistency, and transparency of the combination product 

development and premarket review process by enhancing understanding of both the 

complex regulatory and scientific issues that arise regarding combination products and 

how to work with FDA to address these issues. 

 

3 See https://www.fda.gov/regulatory-information/search-fda-guidance-documents/postmarketing-safetyreporting-combination-products.

4 See https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products. 

5 See the immediately in effect guidance for industry and Food and Drug Administration staff Compliance 

Policy for Combination Product Postmarketing Safety Reporting (April 2019), available at 

https://www.fda.gov/media/111795/download.
Table of Contents

Introduction .........................................................................................1

Description of Combination Products ...............................................................1

Statutorily Mandated Functions of OCP............................................................2

Performance Presented in This Report.............................................................3

Prompt Assignment of Combination Products...............................4

Requirement Workload Trends: FY 2014 to FY 2019 ......................................4

Pre-RFD Workload Performance ..................................................................8

OCP’s Performance on Internal Center- or Office-Requested Product Classifications 

and Center Assignment Consultations............................................................10

OCP’s FY 2019 Accomplishments..................................................................11

Combination Product Premarket Review ......................................12

Number and Types of Combination Products Submitted for Premarket Review12

Requirement Workload Trends: FY 2014 to FY 2019 .....................................13

Inter-Center Consult Requests....................................................................15

Timeliness in Days of the Reviews of Combination Products .........................17

FY 2018 and FY 2019 Review Performance ..................................................19

Premarket Review Facilitation/Oversight.....................................................20

Combination Product Postmarket Activities.................................22

Effective Resolutions of Review Disputes ....................................24

Percentage of Combination Products Reviewed for Which a Dispute Resolution Was 

Requested......................................................................................................24

Policy Activities and Accomplishments........................................25

Regulatory Initiatives ......................................................................................25

Supporting Legislative Initiatives .................................................................25

Streamlining Regulation..............................................................................25

Providing Clarifying Guidance.....................................................................25

Other Policy-Related Activities....................................................................27

Additional Activities and Accomplishments.................................30

Information Technology..................................................................................30

External Outreach ..........................................................................................30

Appendix A: FY 2018 Updated Performance Detail.....................33
Abbreviations

510(k) – premarket notifications

ANDA – abbreviated new drug application

BLA – biologics license application

BsUFA – Biosimilar User Fee Act

CBER – Center for Biologics Evaluation and Research

CDER – Center for Drug Evaluation and Research

CDRH – Center for Devices and Radiological Health

CFR – Code of Federal Regulations

CGMP – current good manufacturing practice

DIA – Drug Information Association

FDA – Food and Drug Administration

FY – fiscal year (October 1 to September 30)

GDUFA – Generic Drug User Fee Act

HDE – humanitarian device exemption

IDE – investigational device exemption

IND – investigational new drug

IT – information technology

MDUFA – Medical Device User Fee Amendments 

MDUFMA – Medical Device User Fee and Modernization Act of 2002

NDA – new drug application

OCC – Office of the Chief Counsel

OCP – Office of Combination Products

PDUFA – Prescription Drug User Fee Act

PMA – premarket approval application

PMOA – primary mode of action

PMSR – postmarketing safety reporting

Pre-RFD – Pre-Request for Designation

RFD – Request for Designation

SMG – Staff Manual Guide

SOP – standard operating procedure
1 FY 2019 OCP Performance Report

Introduction

On October 26, 2002, the Medical Device User Fee and Modernization Act of 2002 (MDUFMA) 

(P.L. 107-250) was signed into law. Among other things, MDUFMA required the U.S. Food and 

Drug Administration (FDA or the Agency) to establish an office “to ensure the prompt 

assignment of combination products to Agency Centers, the timely and effective premarket 

review of such products, and consistent and appropriate postmarket regulation of like products 

to the extent permitted by law.” In response, FDA established the Office of Combination 

Products (OCP) within the Office of the Commissioner. On December 13, 2016, the 21st 

Century Cures Act (Cures Act) was signed into law. Among other things, section 3038 of the 

Cures Act clarified and expanded the duties of OCP to include ensuring the alignment of the

premarket review of combination products. Information about OCP, including the authorizing 

text of MDUFMA as amended by the Cures Act, can be found on the Combination Products 

web site.

6

Description of Combination Products

Title 21 of the Code of Federal Regulations (CFR) (section3.2(e)) states that combination 

products include:

(1) A product comprised of two or more regulated components, i.e., drug/device, 

biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or 

otherwise combined or mixed and produced as a single entity; 

(2) Two or more separate products packaged together in a single package or as a unit and 

comprised of drug and device products, device and biological products, or biological and 

drug products; 

(3) A drug, device, or biological product packaged separately that, according to its 

investigational plan or proposed labeling, is intended for use only with an approved 

individually specified drug, device, or biological product where both are required to 

achieve the intended use, indication, or effect and where upon approval of the proposed 

product the labeling of the approved product would need to be changed, e.g., to reflect a 

change in intended use, dosage form, strength, route of administration, or significant 

change in dose; or,

(4) Any investigational drug, device, or biological product packaged separately that 

according to its proposed labeling is for use only with another individually specified 

investigational drug, device, or biological product where both are required to achieve the 

intended use, indication, or effect.

 

6 Available at www.fda.gov/CombinationProducts/default.htm
2 FY 2019 OCP Performance Report

Some combination products have the potential to provide enhanced therapeutic advantages 

compared to non-combination medical products (i.e., devices, drugs, and biological products)

and incorporate cutting-edge, novel technologies that hold great promise for advancing patient 

care. Combination products may include drug delivery systems, gene therapy systems, 

personalized medicine drug-device combinations, biological-device combinations, applications 

of nanotechnology, and other innovative products.

Statutorily Mandated Functions of OCP

MDUFMA and the Cures Act have established broad responsibilities for OCP that cover the 

regulatory life cycle from product jurisdiction decisions to duties relating to the premarket review 

and postmarket oversight of combination products. However, the primary responsibilities for the

scientific premarket review and the postmarket regulation of combination products remain in the 

three human medical product Centers – the Center for Biologics Evaluation and Research 

(CBER), the Center for Drug Evaluation and Research (CDER), and the Center for Devices and 

Radiological Health (CDRH) – to which they are assigned by OCP. 

Specifically, section 503(g)(8) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 353 

(g)(8)) requires OCP to, among other things:

(1) Promptly assign a Center with primary jurisdiction for a combination product;

(2) Ensure the timely and effective premarket review of combination products by overseeing 

the timeliness of reviews and the alignment of the Agency’s feedback to the sponsor and 

by coordinating reviews involving more than one Center;

(3) Ensure the consistency and appropriateness of the postmarket regulation of like 

products subject to the same statutory requirements to the extent permitted by law;

(4) Resolve disputes regarding the timeliness of the premarket review of combination 

products; and

(5) Review and modify/revise/eliminate, as needed, agreements, guidance documents, or 

practices specific to the assignment of combination products.

Among other activities, OCP serves as a focal point for addressing combination product issues 

raised by FDA’s reviewers and stakeholders and works with the relevant Centers to develop 

guidance documents, regulations, processes, and procedures to clarify and enhance the 

efficiency, consistency, and transparency of the Agency’s regulation of combination products.

In addition, OCP has responsibility for FDA’s actions on all Requests for Designation (RFDs) 

submitted by industry in accordance with 21 CFR part 3, “Product Jurisdiction.” RFDs may 

request (1) a classification of a particular product as a biological product, device, or drug or as a 

combination product, (2) a determination of its Center assignment or both, or both (1) and (2).

RFDs provide a formal legally binding classification and Center assignment response.
3 FY 2019 OCP Performance Report

Performance Presented in This Report

This report presents OCP’s FY 2019 activities and accomplishments. There are key measures 

included in this report that should be made public. These reportable measures support the

mandated functions of OCP. Specifically, this report presents information and data on OCP’s

activities related to the following:

7

· Prompt assignment of combination products 

o Timeliness of the assignment of combination products

· Timely and effective premarket review 

o Number and types of combination products under review

o Timeliness of the reviews of combination products

o Number of premarket reviews of combination products that involved a consulting 

Center

· Consistent and appropriate postmarket regulation 

· Effective resolution of review disputes 

Percentage of combination products for which a dispute resolution, with respect to premarket 

review, was requested.

Unless otherwise noted, all performance data are as of September 30, 2019.

 

7 FDA has initiated various activities related to its implementation of the Cures Act’s requirements for combination 

products, and this report has been modified to provide new information to reflect the Cures Act’s requirements and 

expectations. As the Cures Act implementation proceeds, the Agency will consider what additional information or 

adjustments may be appropriate for subsequent reports. 
4 FY 2019 OCP Performance Report

Prompt Assignment of Combination Products

OCP is required to respond to RFDs to classify a particular product as a biological product, 

device, drug, or combination product and to assign a particular product to the appropriate 

Center (i.e., CBER, CDER, or CDRH). OCP assigns the primary jurisdiction for combination 

products (i.e., the Center assignment) based on the product’s primary mode of action (PMOA) 

(see 21 U.S.C 353(g)(1) and, 21 CFR 3.4(a)) in response to RFDs. RFD submissions are 

subject to a statutory 60-day deadline for FDA response.

8

 OCP also provides responses to PreRequest for Designation (Pre-RFD) requests for assistance regarding product classification and 

assignment.9

Requirement Workload Trends: FY 2014 to FY 2019

In the table below, the total number of RFD determinations (i.e., classifications and assignments

for both combination and non-combination products) in FY 2019 is compared to the previous 5-

year averages. The total number of RFD determinations in FY 2019 increased by 63 percent

compared to FY 2018. RFD determinations for combination products were 40 percent higher 

than the average for the previous 5 years, and RFD determinations for non-combination 

products were 50 percent higher over this 5-year average.

Table 1. RFD Determinations from FY 2014 to FY 201910

RFD Submissions FY 14 FY 15 FY 16 FY 17 FY 18 FY 19

FY 14 to 

FY 18

5-Year 

Average

FY 19

Compared 

to 5-Year 

Average

Total RFD Combination 

Product Classifications/ 

Assignments 

8 2 2 5 8 7 5 +40%

Total RFD Non-Combination 

Product Classifications/ 

Assignments

9 7 2 3 0 6 4 +50%

 

8 OCP also provides assistance to sponsors regarding the preparation of RFDs and works with sponsors who 

disagree with FDA’s classification or assignment determination on potential studies to support a change to the 

determination (21 U.S.C. 353(g)(1)(F)).

9 Responses to Pre-RFD submissions for product classification and jurisdictional assignments do not have a required 

time frame. However, OCP attempts to respond to Pre-RFD submissions in the same time frame as RFDs (i.e., 

within 60 days). Information about Pre-RFD submissions (including the timeliness of OCP responses) is provided in 

the section below titled “Pre-RFD Workload Performance.” 

10 Over the reported 5-year time frame, a decrease in RFD decisions has been accompanied by an increase in the 

number of Pre-RFD assessments provided by OCP. See the section below titled “Pre-RFD Workload Performance” 

for more information.
5 FY 2019 OCP Performance Report

OCP received 50 RFD submissions in FY 2019 and carried over three RFD submissions that 

were undergoing review at the end of FY 2018. Of the 53 total submissions that were reviewed 

in FY 2019, decisions were issued for 13 submissions (25 percent), 35 submissions were found 

to have insufficient information for filing (66 percent), 3 submissions were pending at the end of 

FY 2019 (6 percent)11 and 2 submissions were withdrawn by the sponsor prior to filing (4 

percent).12 OCP also issued one response to a Request for Reconsideration of an RFD 

decision by the 15-day review period, as specified by the regulations. 

 

11 These three submissions were undergoing review at the end of FY 2019 and were carried over to FY 2020.

12 All percent values have been rounded to the nearest number for this entire report.
6 FY 2019 OCP Performance Report

As shown in Table 2, the total number of 

RFD combination product classifications and 

assignments issued in FY 2019 decreased 

by one compared to FY 2018.

As shown in Table 3, the total number of 

RFD non-combination product classifications 

and assignments issued in FY 2019 

increased by six compared to FY 2018. 

FY

14

FY

15

FY

16

FY

17

FY

18

FY

19

Total 8 2 2 5 8 7

CBER 1 0 0 0 1 1

CDER 5 1 1 4 6 4

CDRH 2 1 1 1 1 2

0

5

10

15

20

25

30

35

40

Number of Requests

Table 2. Combination Product 

Determinations.

FY

14

FY

15

FY

16

FY

17

FY

18

FY

19

Total 9 7 2 3 0 6

CBER 2 4 0 1 0 2

CDER 4 1 2 0 0 2

CDRH 3 2 0 2 0 2

0

5

10

15

20

Number of Requests

Table 3. Non-Combination Product 

Determinations.
7 FY 2019 OCP Performance Report

In FY 2019, the 13 RFD determinations were all issued by the statutorily mandated 60-day 

deadline. The average RFD review time was 57 days, with a median review time of 57 days. 

Tables 4 and 5 provide timeliness data by the product type of the issued RFD decision. 

Table 4. Timeliness of Combination Product 

Determinations.

Determination

Product

Assignments

Issued*

Percent

On Time*

Drug-Device 4 100%

Drug-Biologic 1 NA

Device-Biologic 2 100%

Drug-DeviceBiologic 0 NA

Total 7 100%

* Does not include Request for Reconsideration responses, 

which are issued within the 15-day time frame provided by 

21 CFR 3.8. One Request for Reconsideration was 

submitted for a combination product in FY 2019.

Table 5. Timeliness of Non-Combination 

Product Determinations.

Determination

Product

Assignments

Issued*

Percent

On Time*

Drug 2 100%

Biologic 2 100%

Device 2 100%

Total 6 100%

* Does not include Request for Reconsideration responses, 

which are issued within the 15-day time frame provided by 

21 CFR 3.8. No Requests for Reconsideration were 

submitted for a non-combination product in FY 2019.
8 FY 2019 OCP Performance Report

Pre-RFD Workload Performance 

In addition to handling RFDs, OCP provided preliminary feedback in response to Pre-RFD 

submissions for product classification and Center assignment (i.e., Pre-RFD assessments). 

The Pre-RFD process can offer more flexibility than the RFD process, for example, the Pre-RFD 

process allows for more discussions (e.g., teleconferences) between FDA and a sponsor if 

questions arise during the review. In Table 6, OCP’s Pre-RFD submission review workloads 

from FY 2017 to FY 2019 are provided. FY 2019 is the third full year of the “formalized” PreRFD program.13

 

Table 6. OCP’s Pre-RFD Workloads from FY 2017 to FY 2019.

Pre-RFD Assessments FY 17 FY 18 FY 19

Combination Product 

Assessments 44 48 51

Non-Combination Product 

Assessments 34 28 29

Unclassified Assessments* NA 6 3

Total Pre-RFD Assessments 78 82 83

* Pre-RFD assessments may not result in a classification

as a drug, device, biological product, or combination product,

and/or a Center assignment. For instance, products that fall

under this unclassified category may meet the criteria for regulation

solely under section 361 of the Public Health Service (PHS)

Act and 21 CFR part 1271, or sponsor for these products may have 

pursued product assignment and not a classification.

Of the 83 total Pre-RFD assessments, 94 percent were issued by OCP’s internally established 

60-day goal date from OCP’s receipt of sufficient information to provide the requested 

feedback.

14

 In FY 2019, the 60-day review goal was missed for 5 submissions out of a total of

83. The average review time was 52 days, with a median review time of 58 days. The following 

tables (i.e., Tables 7 through 10) provide data on the Pre-RFD feedback for combination 

products and non-combination products based on the products’ classification and the Center 

assignment.

 

13 Formalization of the Pre-RFD program as a distinct OCP activity occurred during FY 2016. Consistent with past 

practice, Pre-RFD data presented in the FY 2016 report continued to be grouped with Center-requested consultations 

(i.e., product classification and jurisdictional requests that have originated with the Centers and not with product 

sponsors). However, Pre-RFDs and Center requested consultations are two different OCP activities. Therefore, 

these two different data groups have been independently reported since FY 2017. Center requested consultations 

are discussed in the following section.

14 OCP does not have a mandated review timeframe for Pre-RFD assessments. However, OCP attempts to review 

Pre-RFD assessments within the same timeframe as RFD submissions (i.e., 60 days).
9 FY 2019 OCP Performance Report

Table 7. Number and Timing of Combination Product Pre-RFD Assessments by Center Assigment.

Classification Pre-RFDs

Issued

Percent

Issued in 60 

Days

Drug-Device 37 95%

Drug-Biologic 1 100%

Device-Biologic 8 88%

Drug-DeviceBiologic 5 100%

Total 51 94%

Table 8. Number and Timing of Combination Product Pre-RFD Assessments by Center 

Assignment.

Center 

Assignment

Pre-RFDs

Issued

Percent

Issued in 60 

Days

CDER 37 95%

CBER 6 83%

CDRH 8 100%

Total 51 94%

Table 9. Number and Timing of Non-Combination Product Pre-RFD Assessments.

Classification Assignments

Issued

Percent

Issued in 60 

Days

Drug 17 94%

Biologic 3 67%

Device 9 100%

Total 29 93%

Table 10. Number and Timing of Non-Combination Product Pre-RFD Assessments by Center 

Assignment.

Center 

Assignment

Pre-RFDs 

Issued

Percent

Issued in 60 

Days

CDER 17 94%

CBER 3 67%

CDRH 9 100%

Total 29 93%
10 FY 2019 OCP Performance Report

OCP’s Performance on Internal Center- or Office-Requested Product 

Classifications and Center Assignment Consultations 

In addition to handling RFDs and Pre-RFDs submitted by industry/sponsors, OCP provides 

classification and Center-assignment feedback for combination and non-combination products 

in response to requests from Centers (i.e., Center-Assignment Consultations (CCA Consults))

and other offices. For instance, Centers may contact OCP for assistance in determining if the

combination product submitted to a Center for review is appropriately assigned to that Center or 

whether the sponsor would need to be referred to OCP for a Pre-RFD/RFD. The number of 

CCA Consults provided by OCP, which identified an assigned Center is presented in Table 11 

below. 

Table 11. Number of CCA Consults by Center from FY 2017 to FY 2019.

Center 

Assignment FY 17 FY 18 FY 19

CDER 29 31 51

CBER 3 3 4

CDRH 16 14 14

Unassigned* 0 2 4

Total 48 50 73

*The term “unassigned” indicates that a determination/assessment of Center assignment was not 

made. This may be the case, for example, if the question before OCP concerns solely product 

classification.

Table 12 reports on OCP’s activities that do not fall within the classification and assignment 

activities reported above, such as responding to questions about process (e.g., how to prepare 

an RFD or Pre-RFD) and providing feedback to sponsors regarding the design of studies (e.g., 

on adequacy to evaluate the PMOA). This category also includes responses to individual email 

queries and meetings and teleconferences that OCP holds with sponsors, which may lead to 

RFDs/Pre-RFDs or obviate the need for them. 

Table 12. Additional Number of OCP’s Product Classification and Assignment Activities from FY 

2017 to FY 2019.

FY 17 FY 18 FY 19

Jurisdiction/Classification Issues 528 529 463
11 FY 2019 OCP Performance Report

OCP’s FY 2019 Accomplishments

Table 13 below highlights OCP’s accomplishments for classification and Center assignment for 

FY 2019. 

Table 13. Specific FY 2019 Accomplishments by OCP.

Type of Activity FY 2019 Accomplishments

Issuing required RFD assignments 

within 60 days

OCP issued all RFD assignments by the statutory 60-day 

determination deadline.

Clarifying standards for product 

classification and preparing guidance 

on this issue

OCP continued to:

· Chair a working group composed of staff from CDER, 

CDRH, CBER, and the Office of the Chief Counsel 

(OCC) to clarify interpretive standards, and to address 

the classification and assignment for challenging 

categories of products

· Pursue and support related policy initiatives, including 

clarifying standards for cross-labeled combination 

product status and clarifying the regulatory status of 

software used with a drug or biological product.

Enhancing the timeliness, 

consistency, and clarity of 

jurisdictional decisions across FDA

OCP continued to facilitate product classification and 

jurisdictional meetings with CBER, CDER, CDRH, and OCC 

staff, to exchange information and discuss challenging product 

classification and assignment issues before FDA.

Developing Part 21 CFR Part 3 

regulations

OCP continued to lead efforts to finalize a rule to amend Part 3 

for clarity and consistency with more recent legislative and policy 

developments.
12 FY 2019 OCP Performance Report

Combination Product Premarket Review 

OCP is responsible for ensuring the timely, effective, and aligned premarket review of 

combination products. This includes overseeing the timeliness of reviews, the alignment of 

feedback to sponsors, and the coordination of reviews in which more than one Center needs to 

participate. 

In 2002, FDA established procedures for CBER, CDER, and CDRH staff to follow when 

requesting, receiving, handling, processing, and tracking inter-Center consults. These

procedures were formally incorporated into the FDA Staff Manual Guide (SMG) 4101 (titled 

“Inter-Center Consult Request Process”). The SMG was significantly updated in June 2018 to 

reflect efforts to improve inter-Center coordination for combination products and enhance the 

timeliness and consistency of inter-Center reviews.

Consistent with OCP’s mandates under the Cures Act, FDA continued its efforts to improve the 

inter-Center consult process for combination products in FY 2019, including a significant update 

to the information technology (IT) system. In addition, OCP continued to (1) enhance its

monitoring of quantitative metrics on inter-Center consults and (2) solicit qualitative input, 

including feedback from users via focus groups and other forums. These efforts have been

used to identify opportunities for improvements in the process, IT system, staffing utilization, 

and resources available to staff. Concurrent with these activities, under the Prescription Drug 

User Fee Act Reauthorization (now PDUFA VI) commitments, FDA initiated an independent 

third-party assessment of regulatory activities for combination products, including premarket 

reviews. A final report from this assessment is due to be issued in FY 2020 and will provide 

further input regarding best practices to broadly improve the inter-Center consult process and 

premarket review activities for combination products.

Number and Types of Combination Products Submitted for Premarket 

Review

FDA is required to report the number and types of combination products submitted for review. 

The following items explain FDA’s performance data that will be presented in this subsection.

· Data on the number and types of combination products submitted for review in FY 2019 by 

CBER, CDER, and CDRH (includes submissions filed or received in FY 2019), as well as 

the timeliness of these reviews. 

· When reporting timeliness in days for the review for CBER-led or CDER-led combination 

products, the PDUFA VI goals were referenced for priority and standard new drug 

applications (NDAs) and applicable biologics license applications (BLAs), the Generic Drug 

User Fee Amendments (now GDUFA II) goals were referenced for the FY 2019 goals for 

abbreviated new drug applications (ANDAs), and the Biosimilar User Fee Amendments (now 

BsUFA II) goals were referenced for the FY 2019 goals for biosimilar BLAs. For CBER-led 

or CDRH-led combination products, Medical Device User Fee Amendments (now MDUFA 

IV) goals were referenced for expedited and original premarket approval applications 

(PMAs), premarket notifications (510(k)s), De Novos, and device BLAs.
13 FY 2019 OCP Performance Report

· Some product review goals, such as for NDAs, are defined by the number of months given 

to review the product. Due to the differences in the numbers of days in each month (28 to 

31), 10 months represents a range from 304 days (such as February 1 to December 1) to 

306 days (such as March 15 to January 15), and 6 months represents a range from 182 

days (such as February 15 to August 15) to 184 days (such as July 15 to January 15).

· The median review times were based on FDA’s first-cycle review performance for PDUFA VI 

goals. For MDUFA IV goals, the median review times were based on the total MDUFA IV 

decision review time. The actual review time was used when only one action was 

measured.

Requirement Workload Trends: FY 2014 to FY 2019

Table 14. FY 2014 to FY 2019 Submission Review Workloads.

Submission/Request FY 14 FY 15 FY 16 FY 17 FY 18 FY 19

Total Combination Products 

(by Center) Submitted for 

Review

317 341 330 566 390 518

As shown in Table 14, the total number of combination products submitted for review increased

from 317 original applications in FY 2014 to 518 original applications in FY 2019. As reflected in 

Table 15, of all combination product submissions, 65 percent were received by CDER, 25 

percent were received by CDRH, and 10 percent were received by CBER.

FY

14

FY

15

FY

16

FY

17

FY

18

FY

19

Total 317 341 330 566 390 518

CDRH 126 129 95 138 102 126

CDER 147 175 199 375 246 339

CBER 44 37 36 53 42 53

0

200

400

600

800

1000

1200

1400

Number of Submissions

Table 15. Combination Product 

Application Submissions by 

Center.
14 FY 2019 OCP Performance Report

Table 16 presents the 518 original applications for combination products received in FY 2019, 

broken down by the identified ten application types and by the product’s initial classification into 

one of nine categories of combination products.

15

 The same table reflecting applications 

received in FY 2018 is updated in Appendix A to reflect corrections and actions as of September 

30, 2019. The majority of the applications received in FY 2019 were original investigational new 

drugs (INDs) (51 percent), followed by 510(k)s (17 percent). Also, the most common 

combination product category was the pre-filled drug delivery device/system (20 percent).

Table 16. Workload by Combination Product Category Number.

Application 

Type 1 2 3 4 5 6 7 8 9

Totals

Original NDAs 16 16 0 0 0 0 0 0 0 32

Original BLAs 2 0 4 0 0 2 2 0 0 10

Original PMAs 0 0 0 4 0 0 1 0 0 5

Original 

510(k)s 18 0 0 63 1 0 8 0 0 90

Original INDs 20 32 27 1 12 54 11 87 19 263

Original 

Investigational 

Device 

Exemptions 

(IDEs)

3 0 0 14 1 0 4 5 3 30

Original

Humanitarian 

Device 

Exemptions 

(HDEs)

0 0 0 0 0 0 0 0 0 0

Original 

ANDAs 27 55 0 0 0 0 0 0 0 82

Biosimilar

BLAs 0 0 5 0 0 0 0 0 0 5

De Novos 0 0 0 1 0 0 0 0 0 1

Totals 86 103 36 83 14 56 26 92 22 518

Combination Product Category Key: 

1 = convenience kit or co-package

2 = pre-filled drug delivery device/system

 3 = pre-filled biologic delivery device/system

4 = device coated/impregnated/otherwise combined with drug

 5 = device coated or otherwise combined with biologic

 6 = drug/biologic combination

 7 = separate products requiring mutually conforming labeling

8 = possible combination based on mutually conforming labeling of separate products

 9 = other type of combination product

 

15 The classifications are presented as initial because adjustments are made to these numbers for each fiscal year to 

reflect corrections and subsequent actions that may inform the classification status, such as the ultimate status of 

products initially placed in category 8 (for certain possible combination products). 
15 FY 2019 OCP Performance Report

Inter-Center Consult Requests

This section reports on the number of inter-Center consults for combination products, a related 

but distinct topic from the number of submissions for combination products. There can, for 

example, be multiple consults for a single combination product submission, or a submission 

may not warrant a consult because relevant expertise resides in the lead Center and 

consultation is not otherwise needed to ensure a consistency of review standards. Combination 

product consults to CDER from other Centers are most often for expertise related to chemistry, 

manufacturing, and controls; biopharmaceutics; or clinical review expertise. Combination 

product consults to CDRH from other Centers are most often for review expertise related to the 

technical (e.g., biocompatibility) and engineering/performance review of delivery devices or for

assessments of facilities for premarket applications; other consult topics include human 

factors/user interfaces, and software.16 

As shown in Table 17, in FY 2019, there were 1,328 inter-Center consults, which was 12

percent higher than the average for the last 5 years but a decrease of 8 percent compared to FY 

2018. 

 

16 Of note, there are other inter-Center consults that may not directly involve combination products, such as 

regarding the use of companion diagnostics with drug or biological products that do not comprise a combination 

product, investigational studies that involve another Center’s products or expertise, and requests for clinical 

expertise that may not be available in a particular Center. Furthermore, cross-Center collaboration also occurs 

through additional pathways (e.g., the Medical Oncology Review and Evaluation team of FDA’s Oncology Center 

of Excellence). These consults are not captured in the counts below but are often conducted under the same process 

as outlined in SMG 4101.

FY

14

FY

15

FY

16

FY

17

FY

18

FY

19

Total 1,013 932 1,130 1,419 1,445 1,328

CBER 48 53 9 105 118 133

CDER 643 499 793 881 867 792

CDRH 322 380 328 433 460 403

 -

 200

 400

 600

 800

 1,000

 1,200

 1,400

 1,600

Number of Requests

Table 17. Inter-Center Consultation 

Requests by Lead/Reviewing Center.
16 FY 2019 OCP Performance Report

In Table 18, the total number of inter-Center consults in FY 2019 is compared to the previous 5-

year averages. 

Table 18. FY 2014 to FY 2019 Inter-Center Consult Workloads.

Submission/Request FY 14 FY 15 FY 16 FY 17 FY 18 FY 19

FY 14 to 

FY 18

5-Year 

Average

FY 19 

Compared 

to 5-Year 

Average

Total Inter-Center Consult 

Requests 1,013 932 1,130 1,419 1,445 1,328 1,188 + 12%

In Table 19, the number of inter-Center consult requests during FY 2019 is broken down by the

lead Center (i.e., the Center requesting the consult) and the consulted Center (i.e., the 

reviewing Center). 

Table 19. Number of Premarket Review Inter-Center Consults for Combination Products by 

Lead and Consulted Center.

Lead Center

Consulted Center

CBER CDER CDRH Number of 

Consults

CBER -- 36 97 133

CDER 29 -- 763 792

CDRH 7 396 -- 403

Total 36 432 860 1,328
17 FY 2019 OCP Performance Report

In Table 20, the number of inter-Center consults is broken down by application type at each 

Center.

Table 20. Number of Premarket Review Inter-Center Consults by Application Type and Lead 

Center.*

Application 

Type

Lead Center

CBER CDER CDRH Number of 

Consults

ANDA -- 124 -- 124

BLA 7 68 -- 75

IND / Pre-IND 103 409 -- 512

NDA 3 186 -- 189

510(k) 7 -- 11 18

De Novo -- -- 15 15

IDE 4 -- 77 81

PMA 1 -- 93 94

Pre-Submission 8 -- 195 203

Other 5 12 17

Total 133 792 403 1,328

 * Inter-Center consult counts include consults for supplements, amendments, etc., not just for 

 original submissions.

Timeliness in Days of the Reviews of Combination Products

FDA is required to report the timeliness of reviews for combination products. Table 21 

summarizes the review types and applicable review performance targets for original NDAs, 

ANDAs, PDUFA BLAs, BsUFA BLAs, PMAs, De Novos, and 510(k)s. PDUFA VI, GDUFA II, 

BsUFA II, and MDUFA IV established review performance goals for many types of drug, device, 

and biological product premarket applications. These goals reflect current expectations about 

the portion of premarket applications that will have an action within a specified time frame. 

Performance goals apply only to a portion of all applications of a certain type, and they do not 

require that every application be reviewed in accordance with the applicable time frame. Typical 

goals range from 50 percent to 90 percent and vary by year. 

· For MDUFA IV performance goals, refer to https://www.fda.gov/media/102699/download.

· For PDUFA VI performance goals, refer to https://www.fda.gov/media/99140/download.

· For GDUFA II performance goals, refer to https://www.fda.gov/media/101052/download. 

· For BsUFA II performance goals, refer to https://www.fda.gov/media/100573/download.
18 FY 2019 OCP Performance Report

Table 21. Performance Goals for Original Applications.

†

User Fee Program Original 

Application Type Review Type Review Within

PDUFA VI NDAs Priority 6 Months

PDUFA VI NDAs Standard 10 Months

PDUFA VI BLAs Priority 6 Months

PDUFA VI BLAs Standard 10 Months

MDUFA IV Expedited and Original PMAs Standard with No Advisory 

Committee Input 180 Days

MDUFA IV Expedited and Original PMAs Standard with Advisory 

Committee Input 320 Days

MDUFA IV 510(k)s Standard 90 Days

MDUFA IV BLAs Priority 6 Months

MDUFA IV BLAs Standard 10 Months

BsUFA II Biosimilar BLAs Standard 10 Months

GDUFA II ANDAs Standard 10 Months

GDUFA II ANDAs Priority 10 Months

GDUFA II ANDAs Priority with Pre-Submission 

Facility Correspondence 8 Months

MDUFA IV De Novos Standard 150 Days

† The timelines for new medical entities and BLAs that fall under PDUFA VI’s “Program” Review Model are 10 months for 

standard applications and 6 months for priority reviews from the 60-day filing date (or 12 months and 8 months respectively,

from the date of submission of the application).

FDA’s premarket review performance information for CBER, CDER, and CDRH is based on a 

fiscal year receipt cohort. This methodology calculates performance information for 

submissions for the fiscal year in which FDA received them, regardless of when FDA acted on 

or approved the submissions. The following subsection, entitled “FY 2018 and FY 2019 Review 

Performance”, updates FDA’s final review performance on the FY 2018 combination product 

submissions and presents FDA’s preliminary review performance on the FY 2019 combination 

product submissions through September 30, 2019.
19 FY 2019 OCP Performance Report

FY 2018 and FY 2019 Review Performance

Table 22 shows the final FY 2018 review goal performance.

Table 22. Final FY 2018 Review Goal Performance.

Original 

Application Type

Review

Type

Review 

Within

Number of 

Combination 

Products

Median or 

Actual Review 

Time (Days)

Range of 

Review Time

(Days)

NDAs Priority 6 Months 4 183 12 to 333

NDAs Standard 10 Months 9 304 301 to 455

BLAs Priority 6 Months 2 288.5 244 to 333

BLAs Standard 10 Months 3 334 303 to 365

Expedited and 

Original PMAs Standard 180 or 320 Days† 3 178 158 to 266

510(k)s Standard 90 Days 61 86 29 to 94

Biosimilar BLAs Standard 10 Months 1 361 361

ANDAs Standard 10 Months 46 299.5 227 to 348

ANDAs Priority 8 Months 2 271.5 248 to 295

ANDAs

Priority with PreSubmission Facility 

Correspondence

8 Months 1 243 243

De Novos Standard 150 Days 2 118 84 to 151

† This includes a review within 180 days for decisions without advisory committee input or a review within 320 days for 

decisions with advisory committee input, respectively.

Table 23 shows preliminary FY 2019 review goal performance through September 30,

2019. 

Table 23. Preliminary FY 2019 Review Goal Performance.

Original 

Application Type

Review

Type

Review 

Within

Number of 

Combination 

Products

Median or 

Actual Review 

Time (Days)

Range of 

Review Time

(Days)

NDAs Priority 6 Months 6 209 94 to 273

NDAs Standard 10 Months 26 304 301 to 393

BLAs Priority 6 Months 2 134.5 113 to 156

BLAs Standard 10 Months 8 298 285 to 298

Expedited and 

Original PMAs Standard 180 or 320 Days† 5 177.5 175 to 180

510(k)s Standard 90 Days 90 87 21 to 90

Biosimilar BLAs Standard 10 Months 4 364 364

ANDAs Standard 10 Months 82 297 224 to 302

ANDAs Priority 8 Months 2 286.5 280 to 293

ANDAs

Priority with PreSubmission Facility 

Correspondence

8 Months 1 242 242

De Novos Standard 150 Days 1 217 217

† This includes a review within 180 days for decisions without advisory committee input or a review within 320 days for 

decisions with advisory committee input, respectively.
20 FY 2019 OCP Performance Report

Premarket Review Facilitation/Oversight

OCP continues to facilitate the premarket review of combination products that raise complex 

regulatory issues. OCP fosters early interactions between industry and FDA to help clearly 

delineate the regulatory pathways for the development of combination products and 

expeditiously review the premarket submissions for these products. Responding to requests 

from both industry and FDA review staff, OCP provides guidance on regulatory challenges 

unique to combination products. OCP also serves as a resource for FDA staff (1) on the 

appropriate use and interpretation of combination product categorization for premarket 

submissions and (2) in determining the correct combination product categories for data 

reporting purposes. Finally, OCP leads or participates in meetings and discussions to ensure 

efficient, effective communication between sponsors and FDA review staff and to align data 

expectations among Centers and for products raising similar regulatory questions. The number 

of OCP’s product-specific documented premarket review actions from FY 2014 to FY 2019 are 

presented in Table 24.

Table 24. Number of OCP’s Documented Premarket Activities from FY 2014 to FY 2019.

FY 14 FY 15 FY 16 FY 17 FY 18 FY 19

FY 14 to 

FY 18

5-Year 

Average

FY 19

Compared 

to 5-Year 

Average

Premarket Review 

Activities 402 225 266 525 321 144 348 -59%

In FY 2019, as shown in Table 24, OCP received 144 requests for product-specific assistance, 

the responses to which contributed to ensuring the timely, effective, and aligned review of 

combination products. This number of requests represents a 59 percent decrease compared to 

the FY 2014 to FY 2018 5-year average.17 Notably, OCP addressed issues including the 

following: 

· Novel drug and biological products combined with new technological delivery systems 

(e.g., emergency use products and complex generic drug-device combination products); 

· Alignment of preclinical and biocompatibility data requests; 

· Review of combination products for rare disease populations; 

· Alignment of potential clinical hold review assessments; 

· Accuracy, consistency, and clarity of the labeling of separately distributed constituent 

parts; 

· Alignment of warning letter considerations with ongoing developmental considerations 

for a platform constituent part of several combination products; 

· Ongoing development considerations of combination products that incorporate mobile 

communication technologies or digital health innovations.

In addition, OCP oversees the inter-Center consults by facilitating a coordination among review 

Centers (i.e., to ensure that reviews of premarket applications are completed in a timely manner 

and meet applicable user fee timelines). Specifically, OCP tracks and monitors all ongoing 

 

17 Please note that the reported decrease in such OCP premarket activities coincided with the 

implementation of the Inter-Center Consult Report, which was launched in FY 2018 and FY 2019, which 

enhanced training and resources for Centers’ staff.
21 FY 2019 OCP Performance Report

inter-Center consult requests; clarifies internal operating procedures, roles, and responsibilities; 

identifies consulting divisions and contacts; clarifies due dates and completion statuses; 

facilitates access to review documents; and works to resolve other barriers to the timely 

completion of consults. OCP also periodically reviews inter-Center consult data requests and 

conducts additional assessments, as needed, to ensure that the inter-Center consult request 

process supports the timely, consistent, and effective review of combination products. 

Additionally, OCP receives and responds to external requests for OCP assistance in resolving 

Center timeliness (i.e., communications and/or clarification of product specific review findings). 

Finally, OCP facilitates the resolution of master file review communication uncertainties.

OCP provides facilitation or assistance to the Centers and industry regarding regulatory and 

scientific issues relating to specific combination products or to specific categories of 

combination products. Detailed accomplishments during FY 2019 are presented in Table 25.

Table 25. OCP’s Provision of Significant Premarket Review Facilitation or Assistance During FY 

2019.

Type of Activity FY 2019 Accomplishments

Providing Significant 

Premarket Review 

Facilitation or Assistance

Provided significant facilitation or assistance with respect to the following 

categories of products and other premarket regulatory issues:

· Novel drug-device cancer therapies;

· Injector delivery systems (e.g., intrathecal and on-body-wearable 

pump infusion systems);

· Medical imaging drugs with photodynamic device activating and 

imaging systems;

· Facilitation of premarket current good manufacturing practice (CGMP)

assessments;

· Application of 21 CFR part 4 to premarket submissions under review;

· Inter-Center review of manufacturing process compliance;

· Inter-Center safety evaluator processes;

· Clarification of the IND human factors protocol submission process 

and the review of these study results;

· Implications of the Drug Supply Chain Security Act on a CDRH-led 

combination product;

· Unique device identifiers and standardized numerical identification;

· Alignment of IND and IDE review requirements for combination 

products;

· Considerations on the Agency’s requirement of two marketing 

applications for a specific combination product.
22 FY 2019 OCP Performance Report

Combination Product Postmarket Activities 

OCP is tasked with ensuring the consistency and appropriateness of postmarket regulation of 

combination products. Hence, FDA is required to describe any improvements in the 

consistency and appropriateness of postmarket regulation of combination products. 

OCP meets the requirement to ensure this consistency and appropriateness by undertaking a 

variety of compliance-related and postmarket activities to help ensure the safety and quality of 

combination products. These compliance-related and postmarket activities include leading the

Agency’s efforts to develop and publish regulations and issue guidances regarding postmarket 

safety reporting (PMSR) and CGMPs for combination products (as discussed more fully in the 

“Policy Activities and Accomplishments” section below), coordinating and overseeing FDA’s

actions relating to novel and complex postmarket safety issues and CGMP compliance 

questions, and facilitating and leading meetings between industry and FDA regarding these 

matters. For example, OCP provides support to FDA’s field investigators on CGMP facility 

inspection issues and on the seizure of products at ports of entry to stop 

adulterated/misbranded products from entering the United States, assists the Agency in 

responding to product defect issues, and provides assistance on enforcement issues to other 

Agency components, including on the development of compliance and enforcement action 

communications such as warning letters. In addition, OCP works with other Agency 

components to develop and present trainings, procedures, IT updates, and other tools to 

enhance the efficiency and consistency of postmarket regulatory activities.

OCP’s FY 2019 accomplishments related to the consistency and appropriateness of postmarket 

regulations are included in Table 26 (see also the “Policy Activities and Accomplishments” 

section below).

Table 26. Documented Product-Specific Postmarket Regulatory Activities from FY 2014 to FY 

2019.

FY 14 FY 15 FY 16 FY 17 FY 18 FY 19

FY 14 to 

FY 18

5-Year 

Average

FY 19 

Compared 

to 5-Year 

Average

Postmarket Regulatory

Activities 110 71 50 74 86 62 78 -21%

OCP engaged in 62 product-specific, postmarket-related matters involving issues such as the 

application of CGMPs and quality system regulations for inspections of combination products, 

the appropriate mechanisms and responsibilities for reporting adverse events, and the 

requirements for registration and listing. This number represents a 21 percent decrease in the 

number of such activities as compared to the prior 5-year average. In addition, at the request of 

the Centers, OCP facilitated or led working groups to assess safety signal evaluations to 

determine the Agency’s response to the safety issue.

These efforts have helped improve the consistency of postmarket regulation in a number of 

ways, including the following:
23 FY 2019 OCP Performance Report

· Enhancing the efficiency and consistency of coordination among the Agency’s

components in support of CGMP inspectional and compliance policies and practices;

· Clarifying stakeholders’ and FDA’s understanding of the PMSR requirements (see also 

the discussion of a final guidance under the “Policy Activities and Accomplishments” 

section below);

· Facilitating the implementation of the PMSR requirements through updates to systems 

and instructions to clarify how to make compliant reports.
24 FY 2019 OCP Performance Report

Effective Resolutions of Review Disputes

When OCP receives a formal request to resolve a dispute regarding the timeliness of the 

premarket review of a combination product, OCP is required to do so. OCP also facilitates 

communications between sponsors and FDA review staff to identify, clarify, and resolve specific 

concerns associated with the review’s timeliness. This facilitation helps prevent the need for 

more formal dispute resolutions.

In addition to sponsor requests for addressing premarket review timeliness issues, OCP may 

receive requests for dispute resolution and/or mediation for other regulatory issues (e.g., interCenter review dispute resolution or requests by product sponsors for assistance either in 

understanding a review division’s intent regarding issued decisions or in resolving differences of 

view regarding regulatory requirements).

Percentage of Combination Products Reviewed for Which a Dispute 

Resolution Was Requested 

FDA is required to identify the percentage of combination products for which a dispute 

resolution, with respect to premarket review, was requested by the combination product’s 

sponsor. FDA received no formal requests for dispute resolution in FY 2019. Therefore, the 

percentage is zero of the total combination product submissions (i.e., based on the total number 

of combination product submissions reported in the “Combination Product Premarket Review”

section of this report). The “Premarket Review Facilitation/Oversight” data in this report provides 

examples of informal facilitation and resolution of issues related to premarket review.
25 FY 2019 OCP Performance Report

Policy Activities and Accomplishments

Regulatory Initiatives

OCP’s activities include leading and assisting with policy initiatives important to the regulation of 

combination products. Examples of such activities pursued in FY 2019 are discussed below 

(and included in the following tables).

Supporting Legislative Initiatives

OCP participated in the development of FDA’s positions in response to congressional inquiries. 

Furthermore, OCP continued its efforts, in coordination with the medical product Centers, to 

implement section 3038 of the Cures Act regarding combination products. Activities in this 

regard included the following: the issuance of new rules and guidance documents and the 

enhancement of standard operating procedures (SOPs), IT improvements, staff training, and 

outreach to stakeholders. OCP also participated in the implementation of section 706 of the 

FDA Reauthorization Act of 2017 (“Fostering Innovation in Medical Imaging”) and was involved 

in the implementation of PDUFA VI activities related to combination products (e.g., developing 

the bridging and human factors guidance documents).

Streamlining Regulation

OCP continued its work on amending FDA’s jurisdictional regulations in 21 CFR part 3, 

considering comments received on the proposed rule,18 to update and clarify them in light of 

legislative and other policy developments.

Providing Clarifying Guidance

OCP collaborated with the medical product Centers to develop and publish regulations,

guidance documents, notices, safety communications, and internal procedures, including the 

following:

· Proposed rule on De Novo classification;19

· Final guidance on PMSR for combination products and compliance enforcement;20

· Final guidance on requests for feedback and meetings under the Q-Submission 

Program21

· Final guidance on devices used with regenerative medicine therapies;22

 

18 Available at https://www.govinfo.gov/content/pkg/FR-2019-05-15/pdf/2019-10321.pdf.

19 Available at https://www.federalregister.gov/documents/2018/12/07/2018-26378/medical-device-de-novoclassification-process

20 Available at https://www.fda.gov/media/111788/download, https://www.fda.gov/media/95120/download

21 Available at https://www.fda.gov/media/114034/download

22 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/evaluation-devices-usedregenerative-medicine-advanced-therapies
26 FY 2019 OCP Performance Report

· Final guidance on the “least burdensome” statutory provisions;23

· Final guidance on the package type and labeling for injectable medical products;24

· Draft guidance on safer technologies;25

· Draft guidance on clinical decision support software;26

· Draft guidance on instructions for use labeling content and format;27

· Draft guidance on premarket pathway principles for combination products;28

· Draft guidance on drug master files for drug-led combination products including 

electronics or software;29

· Draft guidance on peripheral percutaneous transluminal angioplasty and specialty 

catheters - 510(k)- submissions;30

· Federal Register request for comments on prescription drug-use-related software;31

· Federal Register notice regarding FDA’s intent to consider the classification of 

hyaluronic products for the treatment of osteoarthritic pain;32

· Federal Register notice for public meetings on the instructions for the electronic 

reporting of adverse events using the E2B(R3) standard;33

· FDA Safety Communication on using caution with implanted pumps for the intrathecal 

administration of medicines for pain management;34

· FDA Safety Communication warning against the use of teething necklaces, bracelets, or 

other jewelry marketed for relieving teething pain or providing sensory stimulation;35

· SMG 4104 on inter-Center consults for human factors reviews.

36

 

23 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/least-burdensomeprovisions-concept-and-principles

24 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/selection-appropriatepackage-type-terms-and-recommendations-labeling-injectable-medical-products

25 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safer-technologiesprogram-medical-devices

26Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-decision-supportsoftware

27 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/instructions-use-patientlabeling-human-prescription-drug-and-biological-products-and-drug-device

28 Available at https://www.fda.gov/media/119958/download

29 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/type-v-dmfs-cder-ledcombination-products-using-device-constituent-parts-electronics-or-software

30 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/peripheral-percutaneoustransluminal-angioplasty-pta-and-specialty-catheters-premarket-notification

31 Available at https://www.federalregister.gov/documents/2018/11/20/2018-25206/prescription-drug-use-relatedsoftware-establishment-of-a-public-docket-request-for-comments

32 Available at https://www.federalregister.gov/documents/2018/12/18/2018-27351/intent-to-consider-the-appropriateclassification-of-hyaluronic-acid-intra-articular-products

33 Available at https://www.govinfo.gov/content/pkg/FR-2019-03-14/pdf/2019-04730.pdf

34 Available at https://www.fda.gov/medical-devices/safety-communications/use-caution-implanted-pumps-intrathecaladministration-medicines-pain-management-fda-safety

35 Available at https://www.fda.gov/medical-devices/safety-communications/fda-warns-against-use-teethingnecklaces-bracelets-and-other-jewelry-marketed-relieving-teething

36 Available at https://www.fda.gov/media/120204/download
27 FY 2019 OCP Performance Report

In addition, OCP led ongoing cross-Center activities to revise and finalize the published draft

guidance for “Human Factors Studies and Related Clinical Study Considerations in Combination 

Product Design and Development”.

Other Policy-Related Activities

Additional policy-related activities included the following:

· Enhancement of procedures and mechanisms for monitoring and enhancing the 

combination products premarket and postmarket regulatory activities, consistent with 

section 3038 of the 21st Century Cures Act;

· Continued evaluation and updating of procedural and IT systems to enable the 

implementation of the final PMSR rule for combination products;

· Participation in the issuance of SMG 4104 on the inter-Center consults for the review of 

human factors information.37

Tables 27 through 29 identify other policy initiatives in which OCP participated, relating to 

jurisdiction, premarket review, and postmarket regulation, presented by activity type.

Table 27. Additional Jurisdictional Regulatory Initiatives.

Type of Activity FY 2019 Accomplishments

Developing regulations and guidance

Additional OCP jurisdiction-related activities included 

participating in the following Agency rulemaking and guidance 

initiatives:

· Rulemaking on the regulatory status of wound care 

products;

· Rulemaking on the meaning of “protein” in the definition of 

“biological product” in the PHS Act.38

Participating in other inter-Center and 

Agency-wide working groups to clarify 

issues related to product jurisdiction

OCP jurisdiction-related activities included the following:

· Enhancement of the efficiency and transparency of the PreRFD program;

· Classification-related issues for e-cigarettes and other 

products that include tobacco.

 

37 Available at https://www.fda.gov/media/120204/download

38 Available at https://www.govinfo.gov/content/pkg/FR-2019-12-12/pdf/2019-26840.pdf
28 FY 2019 OCP Performance Report

Table 28. Additional Premarket Review Regulatory Initiatives.

Type of Activity FY 2019 Accomplishments

Developing regulations and guidance 

· OCP continued to chair a cross-Center working group to 

finalize a guidance on human factors studies for combination 

products.

· OCP continued to chair a cross-Center working group to 

develop a draft guidance for technical aspects of intravaginal 

ring drug-delivery combination products.

· OCP chaired a cross-Center working group to develop a

guidance for the technical considerations for demonstrating 

reliability of combination product emergency-use injectors.

· OCP led the development of a Cures Act-mandated 

guidance on presubmissions for combination product and 

combination product agreement meetings.

OCP participated in the development of the following: 

· Rulemaking on De Novo classification;

· Guidance on bridging for drug and biologic-led combination 

products;

· Guidance on pre-submission facility inspections for generic 

drugs;39

· Guidance on metered dose inhalers and dry powder 

inhalers;40

· Comments for citizen petition responses for specific types of 

generic combination products;

· Technical considerations for the visual inspection of

particulates in injectable solutions;

· Comments on International Organization for Standardization 

standards development for certain syringes.

Assessing regulatory pathways for 

new products intended to be used 

with another sponsor’s alreadyapproved product

OCP continued to work with the Centers and OCC to assess 

approaches for resolving complex legal and public health issues 

associated with the marketing of products intended for use with 

other legally marketed products.

Participating in other inter-Center and 

Agency-wide working groups to 

clarify issues related to the combined 

use of medical products

OCP led or participated in working groups with Centers and other 

Agency components regarding:

· The appropriate regulatory pathway for novel technology 

diagnostics and biomarkers for use with drug or biological 

products;

· Companion diagnostics;

· Non-prescription drug availability;

· The Agency’s thinking on the regulation of software as drug 

labeling;

· Agency-wide working groups such as FDA’s Task Force on 

Antimicrobial Resistance.

 

39 Available at https://www.fda.gov/media/105794/download

40 Available at https://www.fda.gov/media/70851/download
29 FY 2019 OCP Performance Report

Type of Activity FY 2019 Accomplishments

Coordinating with other Centers

OCP led or participated in working groups with the Centers 

regarding the monitoring and continuous improvement of the 

inter-Center consult process, including IT development and 

enhancement. OCP developed agreements and SOPs regarding 

when and how Centers consult with each other and, when 

needed, OCP for combination product issues.

Table 29. Additional Postmarket Review Regulatory Initiatives.

Type of Activity FY 2019 Accomplishments

Participating in other InterCenter and Agency-wide 

working groups to clarify 

issues related to 

combination products and 

guidance development

· OCP continued to chair working groups relating to PMSR for 

combination products. Work focused on the development of a 

final guidance regarding the final rule and efforts to implement 

the rule, including internal training and development of internal 

SOPs. 

· OCP continued to chair a working group and leadership body to 

support implementation of the final rule on CGMPs for 

combination products, including inspectional activities and 

expectations relating to premarket submissions.

· OCP continued to work with Centers on track and trace 

programs with respect to combination products, including Unique 

Device Identifier, numeric drug coding, and serialized numeric 

identifiers.

· OCP continued to co-chair a committee on combination products 

of the Association for the Advancement of Medical 

Instrumentation that continued work on a technical information 

report on risk management for combination products. 
30 FY 2019 OCP Performance Report

Additional Activities and Accomplishments

Information Technology

OCP continued to coordinate and participate in cross-cutting IT initiatives to enhance the 

infrastructure and update guidance as appropriate to improve the efficiency, consistency, and 

reliability of information systems and communications within and among medical product 

Centers and between FDA and combination product sponsors, and other interested 

stakeholders. OCP launched a new technology platform to facilitate cross-Center collaboration 

for the review of combination products. In light of the final rule on PMSR for combination 

products, OCP also initiated a project to integrate, to the extent feasible, data on combination 

products from different data sources such as premarket systems, registration and listing, and 

adverse event reporting systems from all three medical product Centers into a single point of 

reference to enhance the efficiency and consistency of postmarket safety activities. Finally, 

OCP began work to develop a new electronic system for Pre-RFD and RFDs.

External Outreach

OCP conducted outreach on FDA’s assignment and regulation of combination products by 

meeting and otherwise engaging with trade associations and coalitions (e.g., Combination 

Products Coalition, Advanced Medical Technology Association, Association for Advancement of 

Medical Instrumentation, The Pharmaceutical Research and Manufacturers of America, and the 

Biotechnology Innovation Organization representing the drug, device, biological product, and 

combination product industries, as well as by participating in industry conferences. Discussions 

and presentations focused on a wide range of topics, including emerging issues in combination 

product regulation, the role of OCP, policies and guidance documents under consideration, 

rulemakings, specific categories of combination products, particular regulatory issues, and 

stakeholder priorities for further action. Examples of OCP’s FY 2019 outreach activities are 

included in the table below.

Table 30. Examples of FY 2019 Outreach Activities.

Type of Activity FY 2019 Accomplishments

Presentations and outreach 

activities

OCP participated in a number of outreach activities. The following are 

examples of venues/events for which OCP provided presentations and/or 

educational outreach:

· Drug Information Association (DIA) Pharmacovigilance and Risk 

Management (January 2019);

· 2019 DIA Annual Conference on Combination Products;

· Parenteral Drug Association/FDA Joint Regulatory Conference 2019;

· DIA Annual Meeting 2019;

· Institute of Electrical and Electronics Engineers conference - Microwave 

Theory and Techniques Twin Cities Workshop (December 13, 2018);

· Xavier University Health Combination Products Summit (September 

2019);

· 2018 DIA Combination Products Conference (October 2018);

· 2018 DIA Complex Drug-Device Generic Combination Products 

Conference (October 2018);

· Medical Device Manufacturers Association 2019 FDA Forum;
31 FY 2019 OCP Performance Report

Type of Activity FY 2019 Accomplishments

· 2019 Medtech Summit (Brussels via teleconference);

· 2019 Food and Drug Law Institute Annual Conference.
32 FY 2019 OCP Performance Report

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33 FY 2019 OCP Performance Report

CBER 

42 

(11%)

CDER 

246

(63%)

CDRH

102 

(26%)

Combination Product 

Applications (n = 390)

Appendix A: FY 2018 Updated Performance Detail

The table below reflects the 390 original applications classified into one of nine categories of 

combination products received in FY 2018.

Workload by Combination Product Category Number

Application 

Type 1 2 3 4 5 6 7 8 9

Totals

Original NDAs 1 11 0 0 0 0 1 0 0 13

Original BLAs 1 0 3 0 0 1 0 0 0 5

Original PMAs 0 0 0 2 1 0 0 0 0 3

Original 

510(k)s 7 0 0 50 1 0 2 0 8 68

Original INDs 17 28 34 4 6 40 6 75 5 215

Original IDEs 6 0 0 15 3 0 4 3 6 37

Original HDEs 0 0 0 0 0 0 0 0 0 0

Original 

ANDAs 14 32 0 0 0 0 0 0 0 46

Biosimilar

BLAs 0 0 1 0 0 0 0 0 0 1

De Novos 0 0 0 2 0 0 0 0 0 2

Totals 46 71 38 73 11 41 13 78 19 390

Combination Product Category Key: 

1 = convenience kit or co-package

2 = pre-filled drug delivery device/system

 3 = pre-filled biologic delivery device/system

4 = device coated/impregnated/otherwise combined with drug

 5 = device coated or otherwise combined with biologic

 6 = drug/biologic combination

 7 = separate products requiring mutually conforming labeling

8 = possible combination based on mutually conforming labeling of separate products

 9 = other type of combination product

Workload by Center Lead

The pie chart to the right shows the 

number and percentage of combination 

product applications in FY 2018 by 

Center lead, as of September 30, 2019.
Department of Health and Human Services

Food and Drug Administration

This report was prepared by FDA’s Office of Combination Products in collaboration with the Office of 

Planning and Evaluation, the Center for Biologics Evaluation and Research, the Center for Drug Evaluation 

and Research, and the Center for Devices and Radiological Health. For information on obtaining additional 

copies, contact:

Office of Planning and Evaluation

Food and Drug Administration

 Centerpark One Building, Room # 72040

4041 Powder Mill Road

Beltsville, Maryland 20705

Phone: 301-796-3843

This report is available on FDA’s home page at www.fda.gov and

on OCP’s home page at https://www.fda.gov/combination-products.