FY 2020

PERFORMANCE REPORT

TO CONGRESS

for the 

Office of 

Combination Products

(as required by the

Medical Device User Fee 

and Modernization Act of 2002) 
FY 2020 OCP Performance Report

Commissioner’s Report

I am pleased to submit the fiscal year 2020 annual performance report to Congress for the 

Office of Combination Products (OCP), an office in the U.S. Food and Drug Administration 

(FDA). This report includes data from the 17th full year since OCP was established, which was

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 be handled 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 its

processes for assigning combination products to the appropriate lead Center and that Center’s

regulation. OCP facilitates interactions between industry and FDA to clearly delineate 

regulatory pathways; monitor and adjust processes to ensure a timely and effective, aligned 

premarket review; and help ensure consistent and appropriate postmarket regulation of 

combination products. In addition to handling combination products, OCP classifies and 

assigns products as drugs, devices, and biological products.

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

existing technologies mature. OCP will continue to focus on the most pressing and important 

issues relating to the regulation of combination products. OCP is committed to actively assisting 

industry and FDA’s reviewers in understanding the complexities of this regulatory area. 

FDA looks forward to ensuring success in meeting the unique challenges presented in the 

review and regulation of combination products. 

Janet Woodcock, M.D. 

Acting Commissioner of Food and Drugs
FY 2020 OCP Performance Report

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FY 2020 OCP Performance Report

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 

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

or drug-device-biologic products) to FDA’s Centers; (2) the timely, effective, and aligned 

premarket review of applications for these products; and (3) the consistent and appropriate 

postmarket regulation of combination products subject to the relevant statutory requirements to 

the extent permitted by law.

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

during fiscal year (FY) 2020 (i.e., October 1, 2019, to September 30, 2020). The following 

activities of OCP for FY 2020, of which the first three relate to a mandate listed above, as well 

as OCP’s performance results for each activity, are highlighted in this report: 

1. Prompt Assignment of Combination Products. In FY 2020, 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 two non-combination product RFD decisions, with every 

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

requirement. OCP also provided timely classification and jurisdictional feedback for 79 

separate Pre-Request for Designation submissions. 

2. Timely and Effective Combination Product Premarket Review. In FY 2020, OCP 

received 188 requests for product-specific premarket assistance, the responses to which 

contributed to ensuring OCP’s timely, effective, and aligned review of combination 

products. 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, clarify regulatory standards, address challenging categories of products, update 

the premarket review process, and address developmental considerations for 

combination products.

a. FDA received 559 original premarket applications for combination products in FY 

2020. There were 1,146 inter-Center consulting reviews for combination products 

in FY 2020. Examples of combination product types can be found on the 

Combination Products website.1

 

1 Available at www.fda.gov/CombinationProducts/default.htm.
FY 2020 OCP Performance Report

3. Consistent and Appropriate Postmarket Regulation. In FY 2020, OCP provided 

clarification and support for 113 separate postmarket matters. OCP continued to chair 

FDA working groups to address current good manufacturing practices (CGMP) and 

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

OCP published a Compliance Program for CGMP facility inspections for combination 

products and conducted training and other activities in support of its implementation, 

including continued updates to facility tracking databases. In addition, OCP worked with 

other Agency components to enhance training, databases, and resources to support 

postmarket safety issue investigations and to support implementation of the 2016 PMSR 

rule.2

 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 2020, OCP continued 

to implement section 3038 of the 21st Century Cures Act and to provide direction 

regarding complex policy and procedural questions for combination products, other 

separately distributed medical products intended for combined use, and the classification 

and assignment of medical products. The Combination Products Policy Council, chaired 

by OCP and consisting of senior leaders from all three human medical product Centers 

and the Office of Clinical Policy and Programs, continued to offer support for such OCP 

activities. OCP issued two draft guidances, one on how a combination product sponsor 

can obtain feedback from FDA on scientific and regulatory questions3 and the other on 

technical considerations for demonstrating the reliability of emergency use injectors.

4

 

OCP also issued a Federal Register notice explaining that FDA intends not to pursue a 

potential approach to enable device sponsors to obtain marketing authorization for their 

products labeled for a new use with an approved, marketed drug.

5

 Other topics 

addressed in FY 2020 included human factors, the inter-Center consult process, access 

to relevant postmarket information via a dashboard, the availability of premarket

pathways for combination products, and regulatory considerations for cross-labeled 

combination products and other separately distributed medical products intended for 

combined use. OCP also continued to conduct external outreach activities through 

engagement with stakeholder organizations and through a variety of educational and 

informational presentations to national and international audiences. These activities were 

intended to foster greater efficiency, consistency, and transparency of the combination

product development and premarket review processes by enhancing understanding of 

the complex regulatory and scientific issues that arise for combination products. These 

2 81 FR 92603 (Dec. 20, 2016). See the guidance for industry and Food and Drug Administration staff Compliance 

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

www.fda.gov/media/111795/download. 

3 Available at www.fda.gov/regulatory-information/search-fda-guidance-documents/requesting-fda-feedbackcombination-products.

4 Available at www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerationsdemonstrating-reliability-emergency-use-injectors-submitted-under-bla-nda.

5 Available at www.federalregister.gov/d/2020-09832.
FY 2020 OCP Performance Report

activities were also intended to clarify how stakeholders can work with FDA to address 

these issues and enable FDA to understand and consider stakeholders’ questions and 

concerns. 
FY 2020 OCP Performance Report

 Table of Contents

COMMISSIONER’S REPORT ....................................................................II

EXECUTIVE SUMMARY.......................................................................... IV

INTRODUCTION ........................................................................................ 1

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

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

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

PROMPT ASSIGNMENT OF COMBINATION PRODUCTS....................... 4

Requirement Workload Trends: FY 2015 to FY 2020 .............................................. 4

Pre-RFD Workload Performance Results........................................................... 7

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

and Center-Assignment Consultations ..................................................................... 9

OCP’s FY 2020 Activities and Accomplishments.................................................... 10

COMBINATION PRODUCT PREMARKET REVIEW ...............................12

Number and Types of Combination Products Submitted for Premarket Review..... 12

Requirement Workload Trends: FY 2015 to FY 2020 ............................................ 13

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

Timeliness in Days of the Reviews of Combination Products ................................. 18

FY 2019 and FY 2020 Review Performance Results.............................................. 20

Premarket Review Facilitation/Oversight.......................................................... 21

COMBINATION PRODUCT POSTMARKET ACTIVITIES .......................25

EFFECTIVE RESOLUTIONS OF REVIEW DISPUTES............................27

Percentage of Combination Products Reviewed for Which A Formal Dispute 

Resolution Was Requested .................................................................................... 27

POLICY ACTIVITIES AND ACCOMPLISHMENTS..................................28

Supporting and Implementing Legislative Initiatives ............................................... 28

Streamlining Regulation.......................................................................................... 28

Clarifying Regulatory Policy .................................................................................... 28

Other Policy-Related Activities................................................................................ 30
FY 2020 OCP Performance Report

ADDITIONAL ACTIVITIES AND ACCOMPLISHMENTS .........................34

Information Technology .......................................................................................... 34

External Outreach................................................................................................... 34

APPENDIX A: FY 2019 UPDATED PERFORMANCE DETAIL...............39
FY 2020 OCP Performance Report

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

ICH – International Council for Harmonisation

IDE – investigational device exemption

IND – investigational new drug application

ISO – International Organization for Standardization

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
1 FY 2020 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 FDA 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. In 

addition, section 3038 of the 21st Century Cures Act (Cures Act) (enacted December 13, 2016) 

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 website.6

Description of Combination Products

Title 21 of the Code of Federal Regulations (CFR) (section 3.2(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 2020 OCP Performance Report

Some combination products (1) have the potential to provide enhanced therapeutic advantages 

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

and (2) incorporate cutting-edge, novel technologies that hold great promise for advancing 

patient care. Combination products may incorporate, for example, advanced delivery systems 

and may include 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 lifecycle from decisions relating to product jurisdiction to duties relating to the

premarket review and postmarket oversight of combination products.

7

 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). 

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

(g)(8)) requires OCP to:

(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 

7 Under the Prescription Drug User Fee Act Reauthorization of 2017 (PDUFA VI) commitments, FDA initiated an 

independent third-party assessment of FDA’s regulatory activities for combination products, including premarket 

reviews. A final report from this assessment issued in August, 2020, which is available at 

(www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vi-assessment-combination-product-reviewpractices-pdufa-vi). The report found FDA’s jurisdictional, inter-Center consult request and premarket review 

practices for combination products fundamentally sound but offered recommendations to improve FDA’s efficiency, to 

enhance FDA’s practices through “straightforward” and “minor” refinements to processes, and to address 

technological challenges. These recommendations aligned with ongoing Agency efforts to improve and enhance 

these practice areas, including efforts discussed in this FY 2020 Performance Report.
3 FY 2020 OCP Performance Report

practices specific to the assignment of combination products.

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 U.S.C. 360bbb-2 and 21 CFR part 3, “Product 

Jurisdiction.” RFDs may request (1) a classification of a particular product as a biological 

product, device, drug, or combination product, (2) a determination of the product’s Center 

assignment, or (3) both. FDA’s responses to RFDs, with respect to classifications and/or Center 

assignments, are binding determinations that may only be changed under the conditions 

specified in 21 U.S.C. 360bbb-2 and 21 CFR 3.9.

Performance Results Presented in This Report

This report presents OCP’s fiscal year (FY) 2020 activities and accomplishments. These 

reportable measures address mandated functions of OCP. Specifically, this report presents 

information and data on OCP’s activities related to the following:8

• 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 

o Timeliness of dispute resolutions regarding combination products

Unless otherwise noted, all performance data are as of September 30, 2020.

8 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 implementation of the Cures Act proceeds, the Agency will consider what additional information or 

adjustments may be appropriate for subsequent reports. 
4 FY 2020 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)). (RFD submissions are subject to a statutory 60-

day deadline for FDA response.) OCP also provides responses to Pre-Request for Designation 

(Pre-RFD) requests for assistance regarding product classification and assignment.9

 In 

addition, OCP leads some and supports other Agency efforts to develop and publish 

regulations, issue guidances, and develop other public-facing documents regarding medical 

product classification and assignment (as discussed more fully in the “Policy Activities and 

Accomplishments” section below).

Requirement Workload Trends: FY 2015 to FY 2020

OCP received 58 RFD submissions in FY 2020. In addition, OCP reviewed three RFD 

submissions that were carried over at the end of FY 2019. Of the 61 total RFD submissions that 

were reviewed in FY 2020, nine submissions (15 percent10) had a decision issued, 46 

submissions (75 percent) were found to have insufficient information for filing, four submissions

(seven percent) were pending at the end of FY 2020,

11 and two submissions (three percent)

were withdrawn by the sponsor prior to filing. Of the nine RFD determinations, seven were 

classified as combination products and two were classified as non-combination products.12

In Table 1, the total number of RFD determinations (i.e., classifications and assignments for 

both combination and non-combination products) in FY 2020 is compared to the previous 5

years. 

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.” Tables 7-10 in this report show the percent of pre-RFD 

assessments issued within FDA’s internal goal of 60 days. 

10 All percent values have been rounded to the nearest whole number for this entire report.

11 These four submissions were undergoing review at the end of FY 2020 and were carried over to FY 2021.

12 OCP did not receive any Requests for Reconsideration in FY 2020.
5 FY 2020 OCP Performance Report

Table 1. RFD Determinations from FY 2015 to FY 

2020.

13

RFD Submissions FY 15 FY 16 FY 17 FY 18 FY 19 FY 20

Total RFD Combination 

Product Classifications/ 

Assignments 

2 2 5 8 7 7 

Total RFD Non-Combination 

Product Classifications/ 

Assignments

7 2 3 0 6 2 

In FY 2020, the nine RFD determinations were all issued by the statutorily mandated 60-day 

deadline. The average RFD review time was 58.7 days, with a median review time of 59 days. 

13 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.
6 FY 2020 OCP Performance Report

As shown in Table 2, the total number of RFD 

combination product classifications and 

assignments issued in FY 2020 remained the 

same in FY 2019.

 

As shown in Table 3, the total number of 

RFD non-combination product classifications 

and assignments issued in FY 2020 

decreased by four compared to FY 2019. 

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

Table 4. Timeliness of Combination Product 

Determinations. 

Determination

Product

Assignments

Issued* 

Percent

On Time*

Drug-Device 5 100%

Drug-Biologic 0 NA

Device-Biologic 1 100%

Drug-DeviceBiologic 1 100%

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. No Requests for Reconsideration were 

submitted for a combination product in FY 2020.

Table 5. Timeliness of Non-Combination 

Product Determinations.

Determination

Product

Assignments

Issued*

Percent

On Time*

Drug 0 NA

Biologic 1 100%

Device 1 100%

Total 2 100%

* 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 2020.

FY

16

FY

17

FY

18

FY

19

FY

20

Total 2 5 8 7 7

CBER 0 0 1 1 1

CDER 1 4 6 4 4

CDRH 1 1 1 2 2

0

5

10

15

20

Number of Requests

Table 2. Combination 

Product Determinations.

FY

16

FY

17

FY

18

FY

19

FY

20

Total 2 3 0 6 2

CBER 0 1 0 2 0

CDER 2 0 0 2 1

CDRH 0 2 0 2 1

0

5

10

15

20

Number of Requests

Table 3. Non-Combination 

Product Determinations.
7 FY 2020 OCP Performance Report

Pre-RFD Workload Performance Results 

Now in its fourth formalized program year, OCP continues the Pre-RFD program14 to provide 

preliminary feedback to Pre-RFD submissions for product classifications and Center

assignments (i.e., Pre-RFD assessments). The Pre-RFD process offers more flexibility than the 

RFD process, allowing for more discussions between FDA and a sponsor if questions arise 

during the review. Table 6 shows OCP’s Pre-RFD submission review workloads from FY 2017 

to FY 2020. 

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

to FY 2020. 

Pre-RFD Assessments FY 

17

FY 

18 

FY 

19

FY 

20

Combination Product 

Assessments 44 48 51 47

Non-Combination 

Product Assessments 34 28 29 30

Unclassified

Assessments* 0 6 3 2 

Total Pre-RFD 

Assessments 78 82 83 79

* Pre-RFD assessments may not result in the classification of a product 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 Act and 21 CFR part 1271 or the sponsor for these products 

may have pursued a product assignment and not a classification.

Of the 79 total Pre-RFD assessments completed by OCP in FY 2020, 72 (92 percent) were 

issued by OCP’s internally established 60-day goal date that begins when OCP receives

sufficient information to provide the requested feedback.9

 The average review time for Pre-RFD 

submissions was 55.7 days, with a median review time of 59 days. The following tables (i.e., 

Tables 7 through 10) provide data on the Pre-RFD assessments for combination products and 

14 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 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.
8 FY 2020 OCP Performance Report

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

Table 7. Number and Timing of 

Combination Product Pre-RFD 

Assessments by Center Assignment. 

Classification Pre-RFDs

Issued

Percent

Issued in 

60 Days9

Drug-Device 37 92%

Drug-Biologic 1 100%

Device-Biologic 6 83%

Drug-DeviceBiologic 3 100%

Total 47 91%

Table 8. Number and Timing of 

Combination Product Pre-RFD 

Assessments by Center Assignment. 

Center 

Assignment

Pre-RFDs

Issued

Percent

Issued in 

60 Days9

CDER 33 91%

CBER 6 83%

CDRH 8 100%

Total 47 91%

Table 9. Number and Timing of NonCombination Product Pre-RFD 

Assessments. 

Classification Assignments

Issued

Percent

Issued in 60 

Days9

Drug 15 93%

Biologic 5 80%

Device 10 100%

Total 30 93%
9 FY 2020 OCP Performance Report

Table 10. Number and Timing of NonCombination Product Pre-RFD 

Assessments by Center Assignment. 

Center 

Assignment

Pre-RFDs 

Issued

Percent

Issued in 60 

Days9

CDER 16 94%

CBER 6 83%

CDRH 8 100%

Total 30 93%

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., Classification and Center-Assignment Consultations 

(CCA Consults)) and other FDA offices. For instance, Centers may contact OCP for assistance 

in determining whether 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 submitted to OCP is presented in Table 11. 

Table 11. Number of CCA Consults by Center from FY 

2018 to FY 2020. 

Center 

Assignment FY 18 FY 19 FY 20

CDER 31 51 44

CBER 3 4 4 

CDRH 13 14 27

Unassigned* 2 4 4 

Total 50 73 79

* 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 solely concerns 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 
10 FY 2020 OCP Performance Report

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

whether it is acceptable to evaluate the PMOA). These activities also include responding to 

individual e-mail queries and holding meetings and teleconferences with sponsors, which may 

lead to RFDs/Pre-RFDs or obviate the need for them. In FY 2020, the number of these 

activities was nearly twice that of the previous 2 years. There was not an apparent explanation 

for the increase in activities (e.g., the activity increase was not SARS-CoV-2- or COVID-19-

related).

Table 12. Number of OCP’s Additional 

Product Classification and CenterAssignment Activities from FY 2018 to FY 

2020. 

FY 

18 

FY 

19 

FY 

20

Jurisdiction/Classification 

Activities15 529 463 950

OCP’s FY 2020 Activities and Accomplishments 

Table 13 highlights OCP’s Activities for classification and Center-assignment for FY 2020. 

Table 13. Specific FY 2020 Activities by OCP. 

Type of Activity FY 2020 Activities

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 (1) clarifying standards for cross15 In FY 2021, OCP is working to enhance its ability to track inquiries and other activities, which will likely enable a 

more granular assessment of the queries received and the ability to identify topics that may warrant more guidance.
11 FY 2020 OCP Performance Report

Type of Activity FY 2020 Activities

labeled combination products’ statuses, (2) 

clarifying the regulatory status of software 

used with a drug or biological product, (3) 

determining when container/closures are also 

considered devices, and (4) classifying

articles that meet both the biological product 

and device definitions.

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 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 2020 OCP Performance Report

Combination Product Premarket Review 

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

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

consistency of FDA’s 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 (also referred to 

as “inter-Center consult requests” in this document). These procedures were formally 

incorporated into the FDA Staff Manual Guide (SMG) 4101 (titled “Inter-Center Consult Request 

Process”). FDA updated this SMG in June 2018 to improve inter-Center coordination for 

combination products and to enhance the timeliness and consistency of inter-Center reviews.

Consistent with OCP’s mandates under the Cures Act, in FY 2020, FDA continued its efforts to 

improve the inter-Center consult process for combination products, including completing 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 fora. These efforts have been 

used to identify opportunities for improvements in the inter-Center consult process, FDA’s IT 

systems, FDA’s staffing utilization, and the resources available to staff. OCP also continued to 

lead some and support other Agency efforts to develop and publish regulations, issue guidance

documents, and develop other public-facing documents regarding the premarket review of 

combination products (as discussed more fully in the “Policy Activities and Accomplishments” 

section below).

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 2020

by CBER, CDER, and CDRH (including submissions filed or received in FY 2020), 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 Prescription Drug User Fee Act Reauthorization of 2017 (PDUFA VI) goals 

were referenced for priority and standard new drug applications (NDAs) and applicable 
13 FY 2020 OCP Performance Report

biologics license applications (BLAs), the Generic Drug User Fee Amendments (now 

GDUFA II) goals were referenced for abbreviated new drug applications (ANDAs), and 

the Biosimilar User Fee Amendments (now BsUFA II) goals were referenced for the 

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.

• 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 results 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 2015 to FY 2020

As shown in Table 14, 559 original applications were submitted for review in FY 2020.

Table 14. FY 2015 to FY 2020 Submission Review Workloads. 

Submission/

Request FY 15 FY 16 FY 17 FY 18 FY 19 FY 20

Total 

Combination 

Products 

Submitted 

for Review

341 330 566 390 518 559

As reflected in Table 15, of all combination product submissions, 78 percent were received by 

CDER, 13 percent were received by CDRH, and 9 percent were received by CBER.
14 FY 2020 OCP Performance Report

Table 16 presents the 559 original applications for combination products received in FY 2020, 

broken down by the identified 10 application types and by the product’s initial classification into 

one of nine categories of combination products.16 The same table reflecting applications 

received in FY 2019 has been updated in Appendix A to reflect corrections and actions as of 

September 30, 2020. The majority of the applications received in FY 2020 were original 

investigational new drug applications (INDs) (67 percent), followed by ANDAs (11 percent). 

Also, the most common combination product category was the possible combination based on 

the mutually conforming labeling of separate products (20 percent). 

Table 16. Workload by Combination Product Category Number. 

Application 

Type 1 2 3 4 5 6 7 8 9 Totals

Original NDAs 13 11 0 0 0 0 0 0 2 26

Original BLAs 1 0 11 0 0 1 2 0 1 14

Original PMAs 1 0 0 0 0 0 0 0 0 1

Original 

510(k)s 4 0 0 29 1 0 2 2 0 38

Original INDs 29 41 59 6 8 96 3 102 29 373

Original 

Investigational 0 0 0 16 9 0 7 5 7 44

16 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). 

FY

15

FY

16

FY

17

FY

18

FY

19

FY

20

Total 341 330 566 390 518 559

CDRH 129 95 138 102 126 75

CDER 175 199 375 246 339 434

CBER 37 36 53 42 53 50

0

200

400

600

800

1000

1200

1400

Number of Submissions

Table 15. Combination Product 

Application Submissions by 

Center.
15 FY 2020 OCP Performance Report

Device 

Exemptions 

(IDEs) 

Original

Humanitarian 

Device 

Exemptions

(HDEs) 

0 0 0 0 0 0 0 0 0 0 

Original 

ANDAs 18 45 0 0 0 0 0 0 0 63 

Biosimilar

BLAs 0 0 0 0 0 0 0 0 0 0 

De Novos 0 0 0 0 0 0 0 0 0 0

Totals 66 97 70 51 18 97 12 109 39 559

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

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 be, for 

example, 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 because 

consultation is not otherwise needed to ensure consistent review standards. Combination 

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

manufacturing, and controls; pharmacology and toxicology; biopharmaceutics; human factors; 

or clinical review. Combination product consults to CDRH from other Centers are most often for 

expertise related to the technical (e.g., biocompatibility) and engineering/performance review of 

delivery devices or for assessments of facilities for premarket applications; however, other 
16 FY 2020 OCP Performance Report

CDRH consult topics include human factors/user interfaces and software.17 

OCP monitors the performance of the inter-Center consult process for correctness (e.g., 

ensuring the information in the consult requests are complete, confirming the requests are being 

directed to the correct recipient, etc.) and timeliness (e.g., ensuring that consults allow the 

recipient adequate time to complete the request while accounting for the established product 

review goals, etc.). OCP works with CBER, CDER, and CDRH in identifying potential areas of 

improvement and implementing changes to improve the consult process.

In FY 2020, there were 1,146 inter-Center consults for combination products. Table 17 shows 

the number of FY 2020 inter-Center consults requested by each of the three medical product 

Centers.

In Table 18, the total number of inter-Center consults in FY 2020 is compared to the previous 5

years. 

 

17 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 but are often conducted under the same process outlined in SMG 4101 

(www.fda.gov/media/81927/download). 

FY 15 FY 16 FY 17 FY 18 FY 19 FY 20

Total 932 1,130 1,419 1,445 1,328 1,146

CBER 53 9 105 118 133 124

CDER 499 793 881 867 792 656

CDRH 380 328 433 460 403 366

 -

 200

 400

 600

 800

 1,000

 1,200

 1,400

 1,600

Number of Requests

Table 17. Inter-Center Consult Requests 

by Lead/Reviewing Center.
17 FY 2020 OCP Performance Report

Table 18. FY 2015 to FY 2020 Inter-Center Consult Workloads. 

Submission/Request FY 15 FY 16 FY 17 FY 18 FY 19 FY 20

Total Inter-Center

Consult Requests 932 1,130 1,419 1,445 1,328 1,146

In Table 19, the number of inter-Center consult requests during FY 2020 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 -- 29 95 124

CDER 19 -- 637 656

CDRH 6 360 -- 366

Total 25 389 732 1,146

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 -- 79 -- 79

BLA 6 70 -- 76
18 FY 2020 OCP Performance Report

Investigational 

New Drug 

Application 

(IND) / PreIND

100 380 -- 480

NDA 1 123 -- 124

510(k) 1 -- 4 5

De Novo -- -- 11 11

Investigational

Device 

Exemption 

(IDE) 

-- -- 87 87

PMA 2 -- 76 78

PreSubmission 1 -- 182 183

Other 13 4 6 23

Total 124 656 366 1,146

* Inter-Center consult counts include consults for supplements, amendments, etc. to a marketing

authorization, not just for original submissions.

Timeliness in Days of the Reviews of Combination Products

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

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

ANDAs, Prescription Drug User Fee Act 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. Combination products are subject to the same review performance 

targets as noncombination products, which are determined based on the premarket review 

application type and the User Fee Program to which the application is subject. 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. 
19 FY 2020 OCP Performance Report

• For BsUFA II performance goals, refer to https://www.fda.gov/media/100573/download. 

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 without PreSubmission Facility 

Correspondence

10 Months

GDUFA II ANDAs

Priority with PreSubmission 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 approach 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 2019 and FY 2020 Review Performance

Results,” updates FDA’s final review performance results on the FY 2019 combination product 

submissions and presents FDA’s preliminary review performance results on the FY 2020

combination product submissions through September 30, 2020. 
20 FY 2020 OCP Performance Report

FY 2019 and FY 2020 Review Performance Results

Table 22 shows the final FY 2019 review goal performance results. 

Table 22. Final FY 2019 Review Goal Performance Results.

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 318

NDAs Standard 10 

Months 26 304 297 to 452

BLAs Priority 6 Months 2 134.5 113 to 156

BLAs Standard 10 

Months 362 334 285 to 366

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 63 295 241 to 309

ANDAs

Priority without 

Pre-Submission 

Facility 

Correspondence

10

Months 39 298 273 to 350

ANDAs

Priority with PreSubmission 

Facility 

Correspondence

8 Months 7 240 224 to 242 

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 2020 review goal performance results through September 30, 

2020. 
21 FY 2020 OCP Performance Report

Table 23. Preliminary FY 2020 Review Goal Performance Results.

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 59 to 244

NDAs Standard 10 

Months 5 305 304 to 388

BLAs Priority 6 Months 1 226 226

BLAs Standard 10 

Months 1 364 364

Expedited 

and Original 

PMAs

Standard

180 or 

320 

Days†

1 189 189

510(k)s Standard 90 Days 38 88 0 to 103

Biosimilar

BLAs 

Standard 10 

Months 0 N/A N/A

ANDAs Standard 10 

Months 93 298 91 to 323

ANDAs

Priority without 

Pre-Submission 

Facility 

Correspondence

10

Months 9 298 116 to 203

ANDAs

Priority with PreSubmission 

Facility 

Correspondence

8 Months 6 241 233 to 269

De Novos Standard 150 Days 0 N/A N/A

† 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. 

Premarket Review Facilitation/Oversight

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

regulatory issues or procedural challenges. OCP fosters early interactions between sponsors 

and FDA to help clearly delineate the regulatory pathways for the development of combination 

products and to help ensure the expeditious review of the premarket submissions for these 

products. Responding to requests from both industry and FDA review staff, OCP provides 
22 FY 2020 OCP Performance Report

guidance on regulatory challenges unique to combination products, including topics spanning 

the developmental and review process across all submission types. 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. In addition, OCP leads or participates in productspecific meetings and discussions to ensure efficient, effective communication between 

sponsors and FDA review staff, to align data expectations for products raising similar regulatory 

questions, and to respond to regulatory questions related to combination products.

The number of OCP’s product-specific documented premarket review actions from FY 2015 to 

FY 2020 are presented in Table 24.

Table 24. Number of OCP’s Documented Premarket Activities from 

FY 2015 to FY 2020. 

FY 

15 

FY 

16 

FY 

17 

FY 

18 

FY 

19 

FY 

20

Premarket Review 

Activities 225 266 525 321 144 188

In FY 2020, as shown in Table 24, OCP received 188 requests for product-specific assistance, 

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

combination products.18 Notably, in FY 2020, OCP addressed issues including the following: 

• For SARS-CoV-2- or COVID-19-related product development, OCP provided rapid 

support to the Centers in developing (1) responses to the sponsor about the 

classification and assignment of the applicable product and (2) guidance relevant to that

product;

• Clarification of submission pathways and related development considerations for generic 

combination products;

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

that may have unique risk profiles; 

• Alignment of pharmacology/toxicology and biocompatibility data requests to sponsors; 

18 Decreases in OCP’s premarket activities have coincided with FDA’s ongoing implementation of the updated interCenter consult request processes, launched in FY 2018 and FY 2019, which include updating IT systems, enhancing 

training, and providing other resources for Centers’ staff.
23 FY 2020 OCP Performance Report

• Regulatory considerations for the review of combination products for rare disease 

populations; 

• Cross-Center consistency for potential clinical hold or approvability review assessments; 

• Accuracy, consistency, and clarity of the labeling of separately distributed products 

intended for combined use; and

• Development and labeling considerations for combination products that incorporate 

mobile communication technologies or digital health innovations.

In addition, OCP oversees and facilitates coordination among review Centers under the interCenter consult process to, for example, ensure that reviews of premarket applications are 

completed in a timely manner and meet applicable user fee timelines. OCP tracks and monitors 

all ongoing 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 periodically reviews inter-Center consult request data 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 (i.e., 

communications and/or clarification of product-specific review findings) in resolving Center 

timeliness issues. 

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

hosts premarket meetings with industry and Agency subject-matter experts to provide 

clarifications on the use of master files for combination products.

OCP participated in database test sessions and implementation discussions to ensure 

continued cross-Center access and usability of a new CDER/CBER electronic submissions 

database. Also, OCP provided recommendations to ensure consistent CDRH access to the 

new database and promoted training of this database to CDRH reviewers.

In addition, OCP assists the Centers and industry on regulatory and scientific issues relating to 

specific combination products or to specific categories of combination products. Examples of 

these activities during FY 2020 are presented in Table 25.
24 FY 2020 OCP Performance Report

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

During FY 2020. 

Type of Activity FY 2020 Accomplishments

Providing Significant 

Premarket Review 

Facilitation or 

Assistance 

Provided significant assistance with respect to the following 

categories of products and other premarket regulatory issues:

• Novel drug-device cancer therapies or treatment 

selection technologies;

• Injector delivery systems (e.g., intrathecal and on-bodywearable pump infusion 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;

• Implication of packaging changes during product 

development;

• 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 certain combination products; 

and

• Facilitation of industry and Agency review teams for 

clarification of human factors considerations.
25 FY 2020 OCP Performance Report

Combination Product Postmarket Activities 

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

of combination products. Hence, FDA is required to describe in this report any improvements in 

the consistency and appropriateness of the postmarket regulation of combination products. 

OCP meets the postmarket regulation requirement by undertaking a variety of compliancerelated and postmarket activities to help ensure the safety and quality of combination products. 

These activities include leading the Agency’s efforts to develop and publish regulations, 

guidances, and other public-facing documents regarding postmarketing safety reporting (PMSR) 

requirements 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. In 

addition to policy work, OCP may provide support for FDA’s CGMP facility inspections and the 

inspection of products at ports of entry, assist in responding to product-specific safety signals 

and defect issues, or offer guidance on compliance and enforcement actions. 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 2020 product-specific actions related to the consistency and appropriateness of 

postmarket regulatory activities are reflected in Table 26.

Table 26. Documented Product-Specific Postmarket Regulatory 

Activities from FY 2015 to FY 2020. 

FY 

15 

FY 

16 

FY 

17 

FY 

18 

FY 

19

FY 

20

Postmarket 

Regulatory Activities 71 50 74 86 62 113

OCP engaged in 113 product-specific, postmarket-related matters involving issues such as the 

application of CGMP and quality system regulations for inspections of combination products, the 

appropriate mechanisms and responsibilities for reporting adverse events, and the requirements 
26 FY 2020 OCP Performance Report

for facility registration and product listing. 19 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:

• Clarifying stakeholders’ and FDA’s understanding of the combination product CGMP 

inspectional approach (see also the discussion of a final compliance program under the 

“Policy Activities and Accomplishments” section below); and

• Facilitating the implementation of the PMSR final rule20 requirements through the 

creation of updates to the systems and the development of both tools for postmarket 

staff and other resources for regulated entities that clarify how to prepare compliant 

reports.

19 The increase in FY 2020’s postmarket regulatory activities largely reflects an unusually high volume of technical 

inquiries relating to coming into full compliance with the 2016 final rule on PMSR for combination products by July 31, 

2020, in accordance with the Compliance Policy for the rule (www.fda.gov/files/about%20fda/published/compliancepolicy-combination-product-postmarketing-safety-reporting.pdf). The Compliance Policy delayed full enforcement of 

the rule in light of substantive stakeholder input supporting the need for such delay to ensure applicants sufficient 

time to update reporting and recordkeeping systems and procedures, including their IT systems.

20 81 FR 92603 (Dec. 20, 2016). 
27 FY 2020 OCP Performance Report

Effective Resolutions of Review Disputes 

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

of the premarket review of a combination product, OCP must resolve the dispute. OCP also 

facilitates communications between sponsors and FDA review staff to identify, clarify, and 

resolve specific concerns associated with review timeliness. This facilitation helps prevent the 

need for 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 the intent of a review division’s decision or in resolving differences of view 

regarding regulatory requirements).

Percentage of Combination Products Reviewed for Which A Formal 

Dispute Resolution Was Requested 

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

with respect to premarket review was requested by the combination product’s sponsor. FDA 

received no formal requests for dispute resolution for combination products in FY 2020. 

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 provide examples of informal facilitation and resolution of issues by OCP related to 

premarket review.
28 FY 2020 OCP Performance Report

Policy Activities and Accomplishments 

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

regulation of combination products. Examples of such activities pursued in FY 2020 are 

discussed below and included in the tables to follow. 

Supporting and Implementing 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, the 

enhancement of standard operating procedures, the development of improvements to the IT 

system, the training of staff, and an 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 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,21 to update and clarify the regulations in 

light of legislative and other policy developments.

Clarifying Regulatory Policy

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

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

following:

• Draft guidance on requesting FDA’s feedback on combination products (guidance has 

since been finalized) (12/2020)22

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

21 Available at www.federalregister.gov/documents/2018/05/15/2018-10321/product-jurisdiction. 

22 Available at www.fda.gov/regulatory-information/search-fda-guidance-documents/requesting-fda-feedbackcombination-products. 
29 FY 2020 OCP Performance Report

electronics or software (10/2019)23

• Draft guidance on bridging for drug-device and biologic-device combination products 

(12/2019)24

• Draft guidance on peripheral percutaneous transluminal angioplasty and specialty 

catheters – premarket notification 510(k) submissions (01/2020)25

• Final rule on the definition of “protein” for purposes of the statutory definition of 

“biological product” (2/2020)26

• Draft guidance on restricted delivery systems: flow restrictors for oral liquid drug 

products (3/2020)27

• Draft guidance on the technical considerations for demonstrating the reliability of 

emergency-use injectors submitted under a BLA, NDA, or ANDA (04/2020)28 

• Federal Register notice announcing the Agency’s intention not to pursue a “devices 

referencing drugs” potential approach for sponsors seeking marketing authorization for 

devices labeled for a new use with an approved, marketed drug (5/2020)29

• Final guidance on postmarketing adverse event reporting for medical products and 

dietary supplements during a pandemic (5/2020)30

• Compliance Program 7356.000 Inspection of CDER-led or CDRH-led combination 

products (06/2020)31

• Final guidance on multiple function device products: policy and considerations (7/2020)32

• Final guidance on regulatory considerations for human cells, tissues, and cellular and 

tissue-based products: minimal manipulation and homologous use (7/2020)33

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

24 Available at www.fda.gov/regulatory-information/search-fda-guidance-documents/bridging-drug-device-andbiologic-device-combination-products.

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

26 Available at www.fda.gov/about-fda/economic-impact-analyses-fda-regulations/definition-term-biological-productfinal-regulatory-impact-analysis. 

27 Available at: www.fda.gov/regulatory-information/search-fda-guidance-documents/restricted-delivery-systems-flowrestrictors-oral-liquid-drug-products-guidance-industry. 

28 Available at www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerationsdemonstrating-reliability-emergency-use-injectors-submitted-under-bla-nda. 

29 Available at www.federalregister.gov/d/2020-09832.

30 Available at www.fda.gov/regulatory-information/search-fda-guidance-documents/postmarketing-adverse-eventreporting-medical-products-and-dietary-supplements-during-pandemic. 

31 Available at www.fda.gov/media/138592/download.

32 Available at www.fda.gov/regulatory-information/search-fda-guidance-documents/multiple-function-deviceproducts-policy-and-considerations. 

33 Available at www.fda.gov/regulatory-information/search-fda-guidance-documents/regulatory-considerationshuman-cells-tissues-and-cellular-and-tissue-based-products-minimal. 
30 FY 2020 OCP Performance Report

Other Policy-Related Activities

Additional policy-related activities included the following:

• Enhancement of procedures and mechanisms for monitoring and enhancing 

combination products’ premarket and postmarket regulatory activities, consistent with 

section 3038 of the 21st Century Cures Act;

• Continued the performance of evaluations and updates of procedural and IT systems to 

enable the implementation of the final PMSR rule for combination products;

• Development and provision of training on the PMSR requirements to FDA’s medical 

product Centers’ product safety offices and other staff involved with addressing safety 

signals; and 

• Development and provision of training on the compliance program for combination 

product CGMPs to inspectors in Office of Regulatory Affairs’ medical product programs 

and to medical product Center staff involved with manufacturing and compliance 

activities.

Tables 27 through 29 identify other policy initiatives in which OCP participated that relate to 

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

Table 27. Additional Jurisdictional Regulatory Initiatives. 

Type of Activity FY 2020 Activities 

Developing regulations and 

guidance

OCP jurisdiction-related activities included 

participating in the following Agency rulemaking and 

guidance initiatives:

• Rulemaking and associated policy activities 

relating to the meaning of “protein” in the 

definition of “biological product” in the Public 

Health Service Act34

• Cross-Center working group on the scope and 

significance of cross-labeled combination 

product status

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 Pre-RFD program

• Development of a classification policy for tissue 

and cellular products

34 Available at www.govinfo.gov/content/pkg/FR-2019-12-12/pdf/2019-26840.pdf.
31 FY 2020 OCP Performance Report

Table 28. Additional Premarket Review Regulatory Initiatives. 

Type of Activity FY 2020 Activities

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 the 

technical aspects of intravaginal system

combination products.

• OCP chaired a cross-Center working group to 

develop a guidance for the technical 

considerations for demonstrating the reliability of 

combination product emergency-use injectors.

• OCP led a cross-Center working group to 

complete a Cures Act-mandated guidance on 

obtaining feedback from FDA for combination 

products through application-based meetings and 

combination product agreement meetings.

• OCP led a cross-Center working group to develop 

a guidance on essential performance 

requirements.

• OCP continued to lead a cross-Center working 

group on insulin pump labeling considerations.

• OCP also led efforts to finalize a guidance on 

premarket principles and pathways for 

combination products, update a guidance on the 

application of user fees for combination products, 

develop a revised draft guidance on postmarket 

changes for combination products, and revise 

inter-Center agreements on medical product 

assignment/coordination.

OCP participated in the development of the following 

policy documents: 

• Rulemaking on De Novo classification

• Comments for citizen petition responses for 

specific types of generic combination products
32 FY 2020 OCP Performance Report

Type of Activity FY 2020 Activities

• Technical considerations for the visual inspection 

of particulates in injectable solutions

• Considerations for what constitutes clinical data 

for user fee purposes

• Technical considerations for container closures 

that are also device constituent parts

• Final rule on importation of prescription drugs

• Final guidance on importation of prescription 

drugs

• Proposed rule to amend part 820 to align more 

closely with International Organization for 

Standardization (ISO) 13485 and associated 

amendments to part 4

• International Council for Harmonisation’s (ICH’s) 

Q12 implementation guidance

Assessing regulatory pathways 

for new products intended to be 

used with another sponsor’s 

already approved 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:

• Non-prescription drug availability

• The Agency’s thinking on the regulation of certain 

software output as drug labeling

• Issues such as importation of prescription drugs, 

good guidance practices, and enforcement 

policies

• Considerations for compounded drugs for use 

with devices

Conducting procedural oversight 

and facilitation

OCP led a working group regarding the monitoring 

and continuous improvement of the inter-Center 

consult process, including IT development and 

enhancement. 

Table 29. Additional Postmarket Review Regulatory Initiatives. 
33 FY 2020 OCP Performance Report

Type of Activity FY 2020 Activities

Participating in other InterCenter and Agency-wide 

working groups to clarify issues 

related to combination products 

• OCP continued to chair working groups relating 

to the PMSR requirements for combination 

products. This work focused on implementation 

of the rule, including developing a Memorandum 

of Understanding for engagement between the 

Centers and OCP on postmarket combination 

product issues and developing and delivering 

internal training. 

• OCP continued to lead activities to support 

implementation of CGMP requirements for 

combination products, including developing and 

issuing a compliance program for inspection of 

CDER-led and CDRH-led combination products, 

training inspectional and compliance staff, and 

finalizing a notice on CGMP 

alternatives/flexibilities.

• 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. 
34 FY 2020 OCP Performance Report

Additional Activities and Accomplishments 

Information Technology

OCP continued to coordinate and participate in IT initiatives to enhance the infrastructure and 

improve the efficiency, consistency, and reliability of information systems and communications 

within and across Agency components and with stakeholders. 

 

• OCP implemented four enhancement releases in FY 2020 to improve the Inter-Center 

Consult Request workflow and data capture, including changes to promote consistency 

in postmarketing consult requests for combination products. 

• In light of the final rule on PMSR for combination products, OCP launched a new 

technology platform to integrate, to the extent feasible, data on combination products 

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

systems, 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. 

• OCP launched a new electronic system to harmonize the workflow and data capture for 

Pre-RFDs and RFDs. OCP also conducted a formal pilot with external volunteers of a 

new Pre-RFD and RFD electronic submission process to improve the efficiency and 

completeness of these submissions. 

• OCP provided training, demonstrations, user guides, and other resources to new users 

from all three human medical product Centers for all OCP-led systems. 

External Outreach

OCP conducted outreach on FDA’s classification, assignment, and regulation of combination 

products by engaging with trade associations and coalitions (e.g., Combination Products 

Coalition, Advanced Medical Technology Association, the Pharmaceutical Research and 

Manufacturers of America, and the Biotechnology Innovation Organization), representing the 

drug, device, biological product, and combination product industries. In addition, OCP 

participated in national and international standards development organizations, including cochairing a committee on combination products for the Association for Advancement of Medical 

Instrumentation and supporting the work of ISO, ICH, International Medical Device Regulators 

Forum, and ASTM International. OCP also presented at various industry conferences. 
35 FY 2020 OCP Performance Report

FDA addressed a wide range of topics about which stakeholders have questions, concerns, or 

proposals for Agency consideration. Topics included 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 2020 outreach activities via industry conferences are included in Table 

30. 

Table 30. Examples of FY 2020 Outreach Activities. 

Type of Activity FY 2020 Accomplishments

Presentations and 

outreach activities

The following are examples of venues/events for which OCP 

provided presentations and/or educational outreach:

• Drug Information Association (DIA) Combination Products 

Conference (October 2019)

• Xavier University Health Combination Products Summit 

(October 2019) 

• Combination Products Forum, Berlin, Germany (October 

2019)

• Regulatory Association Professional Society (RAPS) 

Combination Products PMSR Workshop (November 2019)

• International Society of Pharmaceutical Engineers (ISPE) 

Global Pharmaceutical Regulatory Summit (December 

2019)

• Pharmaceutical Development Association (PDA) Optimizing 

Quality Risk Management Conference (December 2019)

• DIA Short Course on Pharmacovigilance for Medication 

Errors (January 2020)

• DIA Advertising and Promotion Regulatory Affairs 

Conference (May 2020)

• FDA Small Business Information Association (SBIA) 

Regulatory Education for Industry: Pharmacovigilance and 

Risk Management Conference (June 2020)

• Combination Products: Reporting Device Information and 

Malfunctions, FDA SBIA Regulatory Education for Industry: 

Pharmacovigilance and Risk Management Conference, 

Webinar (June 2020)

• TOPRA/RAPS Inter-regulatory and Stakeholder Workshop 

on Alignment of Global Combination Products Regulations 
36 FY 2020 OCP Performance Report

Type of Activity FY 2020 Accomplishments

(June 2020)

• ISPE: Roadmap of the Pathways for Combination Products 

(August 2020)

• DIA/FDA “Workshop on complex generic drug-device 

combination products” – Steering Committee to develop the 

October 2020 workshop

• PDA Delaware Valley Chapter and West: The Evolving 

Landscape for Combination Products Defining a Regulatory 

Strategy (September 2020)

• RAPS 2020: Convergence (September 2020) 

• Global Bio Conference 2020, Sponsored by Korean Ministry 

of Food and Drug Safety (September 2020)
37 FY 2020 OCP Performance Report

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38 FY 2020 OCP Performance Report
39 FY 2020 OCP Performance Report

Appendix A: FY 2019 Updated Performance Detail 

The table below reflects the 519 original applications classified into one of nine categories of 

combination products received in FY 2019. 

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 

IDEs 3 0 0 14 1 0 4 5 3 30

Original 

HDEs 0 0 0 0 0 0 0 0 0 0 

Original 

ANDAs 27 56 0 0 0 0 0 0 0 83 

Biosimilar

BLAs 0 0 5 0 0 0 0 0 0 5 

De Novos 0 0 0 0 0 0 0 0 0 0

Totals 86 104 36 83 14 56 26 92 22 519

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
40 FY 2020 OCP Performance Report

Workload by Center Lead

The pie chart to the right shows the 

number and percentage of combination 

product applications in FY 2019 by 

Center lead, as of September 30, 2020.

CBER 

53 

(10%)

CDER 

340

(66%)

CDRH

126 

(24%)

Combination Product 

Applications (n = 519)

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.