Performance Report to Congress

Office of Combination 

Products

FY 2022

(as required by the Medical Device User Fee and 

Modernization Act of 2002)
Executive Summary

The U.S. Food and Drug Administration (FDA or 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 includes ensuring (1) the prompt assignment of combination products (drugdevice, biologic-device, drug-biologic, or drug-device-biologic products)

1

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.

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

accomplishments during fiscal year (FY) 2022 (i.e., October 1, 2021, to September 30, 

2022). This report highlights the following OCP activities for FY 2022: 

A. Prompt Assignment of Combination Products

Sponsors may submit Request for Designation (RFD) submissions to obtain formal 

Agency determinations for the classification of a human medical product (e.g., biological 

product, device, drug, or combination product) and/or for the Center assignment (i.e., 

the lead Center in the case of a combination product) for the product’s premarket review 

and regulation. In FY 2022, OCP issued two combination product and two noncombination product RFD decisions, with every classification and/or assignment 

decision meeting FDA’s 60-day statutory requirement. Alternatively, sponsors may 

submit a Pre-Request for Designation (Pre-RFD) to obtain informal feedback from OCP 

on a product’s classification and/or Center assignment. In FY 2022, OCP provided 

classification and Center assignment feedback for 48 Pre-RFDs. (For more information, 

see the “Policy and Procedural Activities and Accomplishments” section below.)

B. Timely, Effective, and Aligned Combination Product 

Premarket Review

In FY 2022, OCP conducted several activities related to the premarket review of 

combination products. For instance, OCP received 160 requests for product-specific 

premarket assistance, the responses to which contributed to ensuring FDA’s timely, 

effective, and aligned review of combination products. OCP’s efforts enabled sponsors 

to expeditiously address FDA’s concerns and bring products to market more efficiently, 

thereby expediting patient access to new treatment options. In addition, OCP chaired

and/or participated in several inter-Center working groups to examine complex 

1 Examples of combination product types can be found on the Combination Products website, which is

available at https://www.fda.gov/combination-products/about-combination-products/combination-productdefinition-combination-product-types.
regulatory issues, clarify regulatory standards, address challenging categories of 

products, improve the premarket review process, and address developmental 

considerations for combination products. Further, in FY 2022, FDA received 600 

original premarket applications for combination products. There were 1,149 interCenter consulting reviews for combination products in FY 2022. (For more information, 

see the “Policy and Procedural Activities and Accomplishments” section below.)

C. Consistent and Appropriate Postmarket Regulation

In FY 2022, OCP provided clarification and support for 39 separate postmarket matters. 

OCP continued to chair FDA working groups to address current good manufacturing 

practices (CGMP) and postmarketing safety reporting requirements for combination 

products. OCP also continued to work with the human medical product Centers on 

registration and listing issues, postmarket manufacturing compliance, and other 

postmarket regulatory issues pertaining to specific combination products. These 

various efforts furthered FDA’s capabilities to identify and help mitigate potential risks to 

patients associated with products currently on the market. (For more information, see 

the “Policy and Procedural Activities and Accomplishments” section below.)

D. Policy and Procedural Activities and Accomplishments

In FY 2022, OCP continued to implement section 3038 of the 21st Century Cures Act, 

which focuses on enhancing the clarity, predictability, efficiency, and consistency of 

premarket regulatory expectations for combination products, including by ensuring that 

the Agency’s components and staff coordinate appropriately on the premarket review of 

these products and that the Agency’s staff thinking is aligned in conducting these 

reviews. Furthermore, OCP continued to develop policy regarding complex regulatory 

and procedural questions for combination products. OCP also continued to develop 

policy related to both (1) separately distributed medical products intended for combined 

use that are not combination products and (2) the classification and assignment of 

challenging medical products. 

For example, OCP published guidance documents related to principles of premarket 

pathways for combination products2 and published, in the Federal Register, alternative 

or streamlined mechanisms to address CGMP requirements for these products.

3

 Also, 

OCP issued system updates and provided training to enhance the efficiency of the interCenter consult process, the RFD/Pre-RFD review and decision process, and the

combination product postmarketing safety reporting (PMSR) dashboard. 

2 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/principlespremarket-pathways-combination-products.

3 87 FR 56066 (Sep. 13, 2022), available at https://www.govinfo.gov/content/pkg/FR-2022-09-

13/pdf/2022-19713.pdf.
OCP also continued, in FY 2022, to conduct external outreach activities through 

engagement with stakeholder organizations and through a variety of educational and 

informational presentations to national and international audiences and standard-setting 

bodies. These activities were intended to foster a greater understanding of the complex 

regulatory and scientific issues in the developmental, premarket, and postmarket 

settings for combination products; clarify how stakeholders can engage with FDA on 

these issues; enable FDA to understand and respond to stakeholders’ questions and 

concerns; and identify potential areas for regulatory convergence across jurisdictions for 

FDA’s oversight of combination products. 
Table of Contents

I. Introduction ................................................................................................. 1

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

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

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

II. Prompt Assignment of Combination Products ........................................ 5

A. Requirement Workload Trends: FY 2017 to FY 2022 ................................... 5

1. Pre-RFD Workload Performance Results.............................................. 8

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

Classification and Center-Assignment Consultations................................... 12

C. OCP’s FY 2022 Activities and Accomplishments ......................................... 14

III. Combination Product Premarket Review................................................ 15

A. Number and Types of Combination Products Submitted for Premarket 

Review ......................................................................................................... 15

B. Requirement Workload Trends: FY 2017 to FY 2022 ................................. 16

1. Inter-Center Consult Requests ............................................................ 18

C. Timeliness in Days of the Reviews of Combination Products ...................... 22

D. FY 2021 and FY 2022 Review Performance Results................................... 24

1. Premarket Review Facilitation/Oversight............................................. 25

IV. Combination Product Postmarket Activities .......................................... 29

V. Effective Resolutions of Review Disputes.............................................. 32

A. Percentage of Combination Products Reviewed for Which a Formal Dispute 

Resolution Was Requested.......................................................................... 32

VI. Policy Activities and Accomplishments ................................................. 33

A. Supporting and Implementing Legislative Initiatives..................................... 33

B. Streamlining Regulations ............................................................................. 33

C. Clarifying Regulatory Policies ...................................................................... 33
D. Other Policy-Related Activities..................................................................... 35

VIII. Additional Activities and Accomplishments .......................................... 39

A. Information Technology Initiatives................................................................ 39

B. External Outreach ........................................................................................ 40

FY 2021 Updated Performance Detail................................... 42
Acronym List

510(k) Premarket Notification

ANDA Abbreviated New Drug Application

ASTM American Society for Testing and Materials

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

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 of Technical 

Requirements for Pharmaceuticals for Human Use

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
1

I. 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 subject to the 

same statutory requirements 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 incorporated into the Federal 

Food, Drug, and Cosmetic Act, and amended by the Cures Act, can be found on the 

Combination Products website.4

A. Description of Combination Products

Title 21 of the Code of Federal Regulations (CFR) (section 3.2(e)) states that 

combination products include the following:

(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 

4 Available at http://www.fda.gov/CombinationProducts/default.htm.
2

specified investigational drug, device, or biological product where both are 

required to achieve the intended use, indication, or effect.

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

advantages compared to non-combination medical products5(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 drugdevice combinations, biologic-device combinations, applications of nanotechnology, and 

other innovative technologies and scientific advancements.

B. 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 oversight and 

facilitative duties relating to the premarket review and postmarket oversight of 

combination products.6 However, the primary day-to-day responsibilities for the 

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;

5 Throughout this document, the terms “medical product” and “human medical product” may be used 

interchangeably, and they refer to human drugs, devices, biological products, and/or combination 

products regulated by the Center for Biologics Evaluation and Research, the Center for Drug Evaluation 

and Research, or the Center for Devices and Radiological Health.

6 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, is available at 

https://www.fda.gov/industry/prescription-drug-user-fee-amendments/pdufa-vi-assessment-combinationproduct-review-practices-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 the Agency’s ongoing efforts to improve and enhance these practice areas. OCP continues to 

implement the recommendations as discussed in this FY 2021 Performance Report.
3

(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.

OCP serves as a focal point for addressing combination product issues raised by FDA’s 

reviewers and stakeholders and works with the relevant Centers not only to develop 

guidance documents, regulations, processes, and procedures but also to enhance the 

clarity, transparency, efficiency, effectiveness, and consistency 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.” Sponsors may submit RFDs to 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. OCP’s determinations

regarding such classifications and/or Center assignments are binding and may only be 

changed under the conditions specified in 21 U.S.C. 360bbb-2 and 21 CFR 3.9.

C. Performance Results Presented in This Report

This report presents OCP’s FY 2022 activities and accomplishments, including its 

fulfillment of statutory mandates. This report presents information and data on OCP’s 

activities related to the following:

7

· Prompt assignment of combination products

o Timeliness of the classification and 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 

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

combination products, and this report provides new information relating to the Cures Act’s requirements 

and provisions. As implementation of the Cures Act proceeds, the Agency will consider what additional 

information or adjustments may be appropriate for subsequent reports. 
4

consulting Center

· Consistent and appropriate postmarket regulation

o Efficient, effective, and consistent facility inspections

o Efficient and effective product tracking and tracing

o Timely consideration of safety signals

· Effective resolution of review disputes

o Timeliness of dispute resolutions regarding combination products

Unless otherwise noted, all performance data are as of September 30, 2022.
5

II. Prompt Assignment of Combination Products

Sponsors may submit RFD submissions to obtain formal Agency determinations from 

OCP for the classification of a human medical product (e.g., biological product, device, 

drug, or combination product) and/or for the assignment of the lead Center (i.e., CBER, 

CDER, or CDRH) for the product’s premarket review and regulation. 

For combination products, OCP generally assigns the Center with primary jurisdiction 

(the lead Center) 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’s response. RFD decisions help sponsors understand the 

regulatory requirements applicable to their products.

In addition to the above activities, OCP provides informal classification and Center 

assignment responses to Pre-Request for Designation (Pre-RFD) submissions.8 

Further, OCP leads and/or supports other Agency efforts to develop and publish 

regulations, guidance documents, and procedures related to the classification and 

assignment of medical products (which is discussed more fully in the “Policy Activities 

and Accomplishments” section below).

Frequently, sponsors submit RFDs or Pre-RFDs that are not sufficiently complete for 

FDA to file the submissions and conduct its assessment. Many RFDs and Pre-RFDs 

require multiple rounds of filing review before they are accepted for review. In these 

situations, OCP continues to assist sponsors to help ensure they understand the

information needed by OCP to determine the product’s classification and assignment, 

thereby helping ensure that RFD and Pre-RFD submissions will be complete for FDA’s

review. 

A. Requirement Workload Trends: FY 2017 to FY 2022

OCP received 41 RFD submissions in FY 2022. Of the 41 total RFD submissions that 

were received and reviewed in FY 2022, four RFD submissions (10%)9 had a decision 

issued, 3510 RFD submissions (85%) were found to have insufficient information for 

filing, one RFD submission (2%) was withdrawn by the sponsor, and one RFD

submission (2%) was within the 60-day review period at the close of FY 2022. Of the

8 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.” 

9 All percent values are rounded to the nearest whole number for this entire report.

10 Two of 35 RFD submissions were received at the end of FY 2022 with a filing decision due date in FY 

2023. In FY 2023, these two RFDs were found to have insufficient information for filing.
6

four RFD determinations, two were classified as combination products and two were 

classified as non-combination products.

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

assignments for both combination and non-combination products) in FY 2022 is 

compared to the previous 5 years. 

Table 1. RFD Determinations from FY 2017 to FY 2022.

RFD Submissions FY 

17

FY 

18

FY 

19

FY 

20

FY 

21

FY 

22

Total RFD Combination 

Product Classifications/ 

Assignments 

5 8 7 7 1 2

Total RFD NonCombination Product 

Classifications/ 

Assignments

3 0 6 2 2 2

In FY 2022, the four RFD determinations were all issued by the statutorily mandated 60-

day deadline. The average RFD review time was 58 days, with a median review time of 

58 days. Two RFD determinations classified the products as drug-device combination 

products. Two RFD determinations classified the products as non-combination 

products, one as a drug and the other one as a biological product.
7

As shown in Table 2, the total number

of RFD combination product Center 

assignment determinations in FY 2022

increased by one from FY 2021.

As shown in Table 3, the total number of 

RFD non-combination product Center 

assignment determinations in FY 2022

remained the same as in FY 2021.

FY

17

FY

18

FY

19

FY

20

FY

21

FY

22

Total 5 8 7 7 1 2

CBER 0 1 1 1 0 0

CDER 4 6 4 4 1 2

CDRH 1 1 2 2 0 0

0

5

10

Number of Requests

Table 2. Combination 

Product Assignment 

Determinations.

FY

17

FY

18

FY

19

FY

20

FY

21

FY

22

Total 3 0 6 2 2 2

CBER 1 0 2 0 0 0

CDER 0 0 2 1 2 2

CDRH 2 0 2 1 0 0

0

5

10

Number of Requests

Table 3. Non-Combination 

Product Assignment 

Determinations.
8

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 2 100%

Drug-Biologic 0 NA

Device-Biologic 0 NA

Drug-DeviceBiologic 0 NA

Total 2 100%

* OCP did not receive any Requests for Reconsideration 

per 21 CFR 3.8 or appeal requests per 21 CFR 10.75 

related to these determinations for FY 2022.

Table 5. Timeliness of NonCombination Product Determinations.

Determination

Product

Assignments

Issued*

Percent

On Time*

Drug 1 100%

Biologic 1 100%

Device 0 NA

Total 2 100%

* OCP did not receive any Requests for Reconsideration per 

21 CFR 3.8 or appeal requests per 21 CFR 10.75 related to 

these determinations for FY 2022.

1. Pre-RFD Workload Performance Results

OCP continues the Pre-RFD program11 to provide preliminary feedback 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 2022. 

11 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 Centerrequested consultations (i.e., product classification and jurisdictional requests that originated with the 

Centers and not with product sponsors). However, responding to 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.
9

Table 6. OCP’s Pre-RFD Workloads from FY 2017 to FY 2022.

Pre-RFD 

Assessment 

Decisions

FY 

17

FY 

18

FY 

19

FY 

20

FY 

21

FY 

22

Combination Product 

Assessments 44 48 51 47 30 3012

Non-Combination 

Product 

Assessments

34 28 29 30 15 1913

Unclassified 

Assessments* 0 6 3 2 1 0

Total Pre-RFD 

Assessments 75 82 83 79 46 49

* 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 the 

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.

A high percentage of Pre-RFDs cannot be filed because they lack sufficient information 

needed for FDA to initiate a review. OCP received 106 Pre-RFD submissions in FY 

2022. Of the 106 received, 28 Pre-RFD submissions (26%) were complete, 41 PreRFD submissions (39%) were reviewed and not accepted due to their lack of sufficient 

information for OCP to complete an assessment, and 10 Pre-RFD submissions (9%) 

were withdrawn14 by the sponsor. The remaining 27 Pre-RFD submissions (25%) 

received in FY 2022 are under FDA’s review, which has continued into FY 2023. 

Several of these 27 Pre-RFD submissions were impacted by FDA’s pending 

implementation of a federal appellate court’s decision in Genus Med. Techs., LLC v. 

FDA, 994 F.3d 631 (D.C. Cir. 2021) and amendment to section 503 of the Federal 

12 One Pre-RFD was for a constituent part of a combination product; the combination product had been

classified in an earlier RFD.

13 One Pre-RFD response yielded classifications and Center assignments for two products.

14 Prior to withdrawal requests from the sponsors, six Pre-RFDs had not been screened, three Pre-RFDs 

had been “filed” after screening, and one was “not filed” after screening.
10

Food, Drug, and Cosmetic Act.

15

 In FY 2022, OCP completed the review of 4816 total 

Pre-RFDs, of which 28 were received in FY 2022, 18 were received in FY 2021,

17 and 

two were received in FY 2020.

18 Twenty-nine19 Pre-RFD assessments (60%) were 

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

receives sufficient information to review and provide the requested feedback. The 

average review time for Pre-RFD submissions was 95 days, with a median review time 

of 58 days. 

Tables 7 through 10 provide data on FDA’s Pre-RFD assessments for combination 

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

Center assignment. FDA's goal is to complete Pre-RFD assessments within 60 days;

however, this goal is not always achievable. For example, for Pre-RFDs that contain 

substantially more information than is allowable in an RFD (i.e., submitted materials are 

limited to 15 pages), this 60-day goal may not be possible. FDA’s achievement of goal 

timeframes is commensurate with available resources. Additionally, as previously 

mentioned, several Pre-RFD submissions were impacted by FDA’s pending 

implementation of a federal appellate court’s decision in Genus Med. Techs., LLC v. 

FDA, 994 F.3d 631 (D.C. Cir. 2021) and amendment to section 503 of the Federal 

Food, Drug, and Cosmetic Act. The uncertainty from these considerations delayed their 

evaluation.

15 On April 16, 2021, the U.S. Court of Appeals for the District of Columbia Circuit issued the Genus 

decision, holding that FDA cannot classify as a drug any product that meets the device definition in 

section 201(h) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). A Federal Register notice about 

this decision, issued in August 2021, is available at https://www.federalregister.gov/publicinspection/2021-16944/request-for-information-genus-medical-technologies-llc-versus-food-and-drugadministration. In addition, section 3621 of the Food and Drug Omnibus Reform Act of 2022 (FDORA) 

(enacted on December 29, 2022), amended section 503 of the FD&C Act by adding subsection (h) which

specified that certain products were deemed to be drugs under section 201(g) and not devices under 

section 201(h) of the FD&C Act.

16 This number differs from the number of assessments (i.e., 49) in Table 6 because one Pre-RFD 

submission yielded two classifications and Center assignments.

17 The initial submissions of the 18 Pre-RFDs received in FY 2021 lacked sufficient information to be

accepted by FDA for review. After several iterations of Additional Information requests to the sponsors, 

nine were accepted for review at the end of FY 2021, and the other nine were accepted for review in FY 

2022.

18 The initial submissions of the two Pre-RFDs received in FY 2020 lacked sufficient information to be 

accepted by FDA for review. They were finally accepted for review in FY 2021 after several iterations of 

Additional Information requests had been made to the sponsor.

19 This number differs from the number of Pre-RFDs received/completed in FY 2022 (i.e., 28) because 

one Pre-RFD submission yielded two classifications and Center assignments.
11

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

Product Classification.

Classification Pre-RFDs

Issued

Percent

Issued in 60 

Days

Drug-Device 25 60%

Drug-Biologic 3 67%

DeviceBiologic 2 50%

Drug-DeviceBiologic 0 N/A

Total 30 60%

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 17 70%

CBER 2 50%

CDRH 11 45%

Total 30 60%
12

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

by Product Classification.

Classification Assignments

Issued

Percent

Issued in 60 

Days

Drug 9 78%

Biologic 1 0%

Device 9 55%

Total 19 63%

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 10 70%

CBER 2 50%

CDRH 7 57%

Total 19 63%

B. OCP’s Performance on Internal Center- or OfficeRequested Product Classification 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 noncombination products in response to requests from FDA’s Centers/Offices (i.e., 

Classification and Center-Assignment Consultations (CCA Consults)). 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.
13

Table 11. Number of CCA Consults by Center from FY 2019 to FY 2022.

* 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 or if the product is not regulated by a human medical product Center. 

Table 12 details additional OCP activities related to product classification and Center 

assignment that do not fall within the classification and assignment activities reported 

above. These additional activities include responding to email queries regarding the 

Pre-RFD and/or RFD processes, providing feedback to sponsors regarding the design

of their studies to evaluate the PMOA of a combination product, and/or holding 

informational meetings/teleconferences with sponsors that plan to submit RFD or PreRFD submissions. 

Table 12. Number of OCP’s Additional Product Classification and CenterAssignment Activities from FY 2019 to FY 2022.

FY 19 FY 2021 FY 21 FY 22

Jurisdiction/Classification 

Activities 463 950 375 235

20 Prior to FY 2021, CCA Consults that were determined to be unassigned—due to the sponsor being 

referred to OCP to request product classification or Center-assignment feedback via a Pre-RFD or RFD—

were captured as an additional activity, as can be seen in Table 12. Due to system enhancements in FY 

2021, OCP now shows these as unassigned CCA Consults in Table 11.

21 There was not an obvious cause for the increase in additional product classification and Centerassignment activities in FY 2020. 

Center 

Assignment FY 19 FY 20 FY 21 FY 22

CDER 51 44 35 35

CBER 4 4 8 7

CDRH 14 27 23 12

Unassigned* 4 4 3320 21

Total 73 79 99 75
14

C. OCP’s FY 2022 Activities and Accomplishments 

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

2022. 

Table 13. Specific FY 2022 Activities by OCP.

Type of Activity FY 2022 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, and CBER to clarify 

interpretive standards and to address the 

classification and assignment for 

challenging categories of products and

· Pursue and support related policy 

initiatives, including (1) clarifying standards 

for cross-labeled combination product 

classification and assignment, (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 21 CFR part 3 for clarity and consistency 

with more recent legislative and policy 

developments.
15

III. 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”).

22

 FDA updated this SMG in June 2018 to improve interCenter 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 2022, FDA continued its 

efforts to improve the inter-Center consult process for combination products, including 

completing significant updates 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 surveys and 

direct user interactions. 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, which ultimately ensures an efficient 

review process and promotes alignment of Agency efforts. OCP also continued to lead 

or support some Agency efforts to develop and publish regulations, guidance

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

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

Accomplishments” section below).

A. 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 2022 by CBER, CDER, and CDRH (including submissions filed or received in 

FY 2022), as well as the timeliness of these reviews. 

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

22 See https://www.fda.gov/media/81927/download.
16

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 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.

B. Requirement Workload Trends: FY 2017 to FY 2022

As shown in Table 14, 906 original applications were submitted for review in FY 2022.

Table 14. FY 2017 to FY 2022 Submission Review Workloads.

Submission/Request FY 17 FY 18 FY 19 FY 20 FY 21 FY 22

Total Combination 

Products Submitted for 

Review

566 390 518 557 596 906
17

As reflected in Table 15, of the original combination product applications received, 56% 

were received by CDER, 11% were received by CDRH, and 33% were received by 

CBER. The increase in combination product applications received by CBER between 

FY 2021 and FY 2022 can be attributed to its updated tracking procedures.

Table 16 presents the 906 original applications for combination products received in FY 

2022, broken down by the identified 10 application types and by the product’s initial 

classification into one of nine categories of combination products.23 The same table 

reflecting applications received in FY 2021 has been updated in Appendix A to reflect 

corrections and actions as of September 30, 2022. The majority of the applications 

received in FY 2022 were original investigational new drug applications (INDs) (72%), 

followed by ANDAs (10%). Also, the most common combination product category was 

the pre-filled biologic delivery device/system (35%).

23 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 16 FY 17 FY 18 FY 19 FY 20 FY 21 FY 22

Total 330 566 390 518 557 596 906

CDRH 95 138 102 126 75 93 101

CDER 199 375 246 339 432 464 503

CBER 36 53 42 53 50 39 302

0

200

400

600

800

1000

1200

1400

Number of Submissions

Table 15. Combination Product 

Original Applications Submitted, by 

Center.
18

Table 16. Workload by Combination Product Category Number.

Application Type 1 2 3 4 5 6 7 8 9 Total

Original NDA 4 18 0 0 0 0 1 0 2 25

Original BLA 2 1 11 0 0 2 0 0 3 19

Original PMA 0 0 0 2 0 0 0 0 2 4

Original 510(k) 4 1 0 41 0 0 7 1 3 57

Original IND 144 41 307 6 10 46 11 73 16 654

Original 

Investigational 

Device Exemption 

(IDE)

3 1 0 35 4 1 4 1 4 53

Original 

Humanitarian Device 

Exemption (HDE)

0 0 0 0 0 0 0 0 0 0

ANDA 13 75 0 0 0 0 0 0 6 94

Biosimilar BLA 0 0 0 0 0 0 0 0 0 0

De Novo 0 0 0 0 0 0 0 0 0 0

Total 170 137 318 84 14 49 23 75 36 906

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

1. 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. 

Unlike submission data, these data reflect consultations relating to original applications 

and supplements to combination product applications, as well as consultations relating 

to postmarket oversight for combination products. Consultations between Centers are

expected during FDA’s premarket review of most combination products; these 

consultations help ensure that relevant FDA expertise, as well as consistency in FDA’s

regulatory practice, is applied to each review.

There can be, for example, multiple consults for a single combination product 

submission or, alternatively, a submission may not warrant a consult because (1) the 

relevant expertise resides in the lead Center and (2) a 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 
19

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; 

other CDRH consult topics include human factors and software.24 

OCP oversees and facilitates coordination among review Centers under the inter-Center 

consult process to ensure consults are completed in a timely manner. For example, 

OCP monitors ongoing inter-Center consult requests for correctness (e.g., ensuring the 

information in the consult requests are complete and confirming the requests are being 

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

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

product review goals); clarifies internal operating procedures, roles, and responsibilities

related to the inter-Center consult process; helps identify consulting divisions and 

contacts; facilitates consultant access to review documents; and manages help desks. 

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 works with CBER, CDER, and CDRH in identifying potential areas of improvement 

and implementing changes to improve the consult process. An efficient and effective 

inter-Center consult request process helps Centers meet their user fee performance 

commitments and promotes alignment of Agency efforts, all of which ultimately helps 

bring new treatment options to patients sooner.

In FY 2022, there were 1,149 inter-Center consults for combination products. Table 17 

shows the number of FY 2022 inter-Center consults requested by each Center.

24 Of note, there are other inter-Center consults that may not directly involve combination products. For 

example, consults regarding the use of companion diagnostics with drug or biological products that do not 

comprise a combination product, investigational studies of a non-combination product that involve another 

Center’s products or expertise, requests for clinical expertise that may not be available in a particular 

Center, and communications between Centers to determine whether postmarket safety events or signals 

regarding a non-combination product warrant further investigation. Furthermore, cross-Center 

collaboration 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 (see 

http://www.fda.gov/media/81927/download).
20

In Table 18, the total number of inter-Center consults in FY 2022 is compared to 

the previous 5 years. 

Table 18. FY 2017 to FY 2022 Inter-Center Consult Workloads.

Submission/Request FY 17 FY 18 FY 19 FY 20 FY 21 FY 22

Total Inter-Center 

Consult Requests 1,419 1,445 1,328 1,146 1,202 1,149

In Table 19, the number of inter-Center consult requests during FY 2022 is broken down 

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

(i.e., the reviewing Center).

FY 17 FY 18 FY 19 FY 20 FY 21 FY 22

Total 1,419 1,445 1,328 1,146 1,202 1,149

CBER 105 118 133 124 119 106

CDER 881 867 792 656 661 665

CDRH 433 460 403 366 422 378

 -

 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.
21

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

and Consulted Center.

Lead 

Center Consulted Center

CBER CDER CDRH CVM* OC

Number 

of 

Consults

CBER -- 39 66 1 -- 106

CDER 18 -- 643 -- 4 665

CDRH 10 368 -- -- -- 378

Total 28 407 710 1 4 1,149

* In addition to consultations to CBER, CDER, and CDRH, the Center for Veterinary Medicine (CVM) may be consulted either 

(1) when a unique aspect of a product’s indication, formulation, design, or performance raises concerns that require review by 

another Center or (2) when the expertise to review a particular aspect of the product resides in another Center. The inclusion of 

CVM in the inter-Center consult process, when appropriate, ensures a comprehensive review of the product.

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

each Center.

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

Application Type

Lead Center

CBER CDER CDRH Number of 

Consults

ANDA -- 92 -- 92

BLA 10 111 -- 121

IND/Pre-IND 91 363 -- 454

NDA -- 94 -- 94

510(k) -- -- 17 17

De Novo -- -- 4 4

IDE -- -- 117 117

PMA 2 -- 95 97

Pre-Submission 2 -- 145 147

Other** 1 5 -- 6

Total 106 665 378 1,149

* Inter-Center consult counts include consults for supplements, amendments, etc. to a marketing authorization, not 

just for original submissions.

** For example, an inter-Center consult related to an Emergency Use Authorization may fall in this “Other” 

category.
22

C. 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. 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 timeframe. Typical 

goals range from 50% to 90% 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.
23

Table 21. Performance Goals for Original Applications

User Fee 

Program

Original 

Application 

Type

Review Type Review Goal 

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

MDUFA IV De Novos Standard 150 Days

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 Pre-Submission 

Facility Correspondence 8 Months

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 2021 and FY 2022 Review Performance Results,” updates FDA’s final review 

performance results on the FY 2021 combination product submissions and presents 

FDA’s preliminary25 review performance results on the FY 2022 combination product 

submissions through September 30, 2022.

25 Preliminary means that the numbers are based on final decisions at the time of the data run and might 

change.
24

D. FY 2021 and FY 2022 Review Performance Results

Table 22 shows the final

26 FY 2021 review goal performance results. Review goal 

performance data are based on the fiscal year receipt cohort. 

Table 22. Final FY 2021 Review Goal Performance Results.

Original 

Application 

Type

Review

Type

Review 

Goal 

Within

Number of 

Combination 

Products

Median or 

Actual 

Review 

Time 

(Days)

Range of 

Review 

Time

(Days)

NDAs Priority 6 Months 13 182 150 to 367

NDAs Standard 10 

Months 28 303 6* to 425

BLAs Priority 6 Months 3 224 182 to 245

BLAs Standard 10 

Months 6 364 336 to 456

Biosimilar 

BLAs Standard 10 Months 1 361 361

Expedited 

and Original 

PMAs

Standard

180 or 

320 

Days

4 178 158 to 266

510(k)s Standard 90 Days 45 86 0 to 230

De Novos Standard 150 

Days 2 215 198 to 231

ANDAs Standard 10 

Months 84 301 287 to 600

ANDAs

Priority without 

Pre-Submission 

Facility 

Correspondence

10 

Months 28 302 287 to 464

ANDAs

Priority with PreSubmission 

Facility 

Correspondence

8 Months 8 240 230 to 331

* This NDA was closed after 6 days because the user fees were not paid.

** These numbers include either a review within 180 days for decisions without advisory committee input or a review within 320 days 

for decisions with advisory committee input, respectively. 

26 Final refers to the time in which all submissions in a cohort receive a final decision or are sufficiently 

complete for FDA to determine whether the review goal has been met.
25

Table 23 shows preliminary FY 2022 review goal performance results through 

September 30, 2022. 

Table 23. Preliminary FY 2022 Review Goal Performance Results.

Original 

Applicatio

n Type

Review

Type

Review 

Goal 

Within

Number of 

Combination 

Products

Median 

or Actual 

Review 

Time 

(Days)

Range of 

Review 

Time

(Days)

NDAs Priority 6 

Months 6 181 133 to 243

NDAs Standard 10 

Months 8 303 285 to 365

BLAs Priority 6 

Months 1 231 231 to 231

BLAs Standard 10 

Months 3 365 365 to 365

Biosimilar 

BLAs Standard 10 Months 0 N/A N/A

Expedited 

and Original 

PMAs

Standard

180 or 

320 

Days

3 107 90 to 178

510(k)s Standard 90 Days 48 72 0 to 374

De Novos Standard 150 

Days 0 N/A N/A

ANDAs Standard 10 

Months 60 301 289 to 424

ANDAs

Priority without 

Pre-Submission 

Facility 

Correspondence

10 

Months 51 300 238 to 413

ANDAs

Priority with PreSubmission 

Facility 

Correspondence

8 

Months 9 238 226 to 244

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. 

1. Premarket Review Facilitation/Oversight

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

complex regulatory issues, scientific/technical concerns, or procedural challenges. 
26

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’s review staff, OCP provides 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 on the appropriate use and interpretation of combination product 

categorization for premarket submissions and in determining the correct combination 

product categories for data reporting purposes. In addition, OCP leads or participates in 

product-specific meetings (1) to ensure efficient and effective communications between 

sponsors and FDA’s review staff and between FDA’s review staff from different Centers,

(2) to align data expectations for products raising similar regulatory questions, and (3) to 

respond to regulatory questions related to combination products.

The number of OCP’s product-specific premarket review actions from FY 2017 to FY 

2022 are presented in Table 24. In particular, in FY 2022, OCP received 160 requests 

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

timely, effective, and aligned review of combination products.27 

Table 24. Number of OCP’s Premarket Activities from FY 2017 to FY 2022.

FY 

17

FY 

18

FY 

19

FY 

20

FY 

21

FY 

22

Premarket Review 

Activities 525 321 144 188 124 160

Notably, in FY 2022, issues addressed by OCP included the following: 

· Clarification of submission pathways and related development considerations for 

investigational combination products with separately distributed constituent parts;

· Alignment of data considerations for simulated shipping studies and sharps 

protection features; 

· Regulatory considerations for the review of combination products for biosimilar 

prefilled autoinjectors;

· Cross-Center consistency for when the submissions of two marketing 

applications for combination products are appropriate; 

27 Decreases in OCP’s premarket activities have coincided with FDA’s ongoing implementation of the 

updated inter-Center consult request processes, launched in FY 2018 and FY 2019, which include 

updating IT systems, enhancing training, and providing other resources for Centers’ staff.
27

· Clarification for the use of and type of master files; and

· Developmental and labeling considerations for combination products that 

incorporate mobile communication technologies or digital health innovations.

In addition to addressing these issues, OCP completed the following premarket 

activities during FY 2022:

· OCP led an inter-Center working group to align the Agency master file 

processes; 

· OCP hosted premarket meetings with industry to provide clarifications on the 

proper use of master files for specific combination products; and

· OCP assisted 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 are presented in Table 25.
28

Table 25. Other Significant Premarket Review Facilitation or Assistance Provided 

by OCP in FY 2022.

Type of Activity FY 2022 Accomplishments

Providing Significant 

Premarket Review 

Facilitation or 

Assistance

OCP provided significant assistance with:

· Novel drug-device cancer therapies or treatment delivery 

technologies;

· Injector delivery systems (e.g., intranasal systemic 

delivery);

· Current good manufacturing practice (CGMP) 

requirements under 21 CFR part 4; 

· Ophthalmic products in light of Genus Med. Techs., LLC v. 

FDA;

· The IND human factors protocol submission process and 

the review timeline for IND study results;

· Aligning the IND and IDE review requirements for 

combination products;

· The suitability of a single application for a combination 

product or a separate application for each constituent part;

· The consistency of the review of on-body wearable 

injection or infusion systems and combination products that 

includes software;

· Drug-device polymer interactions in implants;

· Resolving a disagreement between the review team and 

the application holder’s request that the review team

provide more information on how to resolve deficiencies;

· The compatibility of needleless syringes with a Lueractivated valve; and

· Clarifying what regulatory requirements and premarket 

review pathways apply to certain products in light of the 

ruling in Genus Med. Techs., LLC v. FDA, which held that

products (other than combination products) that meet both 

the drug and the device definitions must be regulated as 

devices.
29

IV. Combination Product Postmarket Activities 

The Center to which a combination product is assigned for premarket review has 

primary jurisdiction for the regulation of the combination product, including for ensuring 

compliance with postmarketing regulatory requirements and performing postmarket 

surveillance. OCP is tasked with ensuring the consistency and appropriateness of the 

postmarket regulation of combination products. 

The right balance of premarket and postmarket oversight activities can facilitate timely 

patient access to safe and effective products. Consistent and appropriate 

postmarketing regulatory requirements help the Agency detect, prevent, and respond 

quickly to product safety or quality problems, thereby minimizing the risk of these 

problems for patients and other users. Manufacturing controls and activities to assess 

CGMP compliance, such as facility inspections, help ensure that marketed products 

remain safe and effective. Postmarket surveillance activities, including postmarketing 

safety reporting, are also critical to protect patients from the risks associated with 

products currently on the market. Combination products pose particular challenges due 

to their complexity and to the range of scientific, technical, and regulatory issues that 

can arise.

OCP undertakes a variety of activities related to manufacturing controls and postmarket 

surveillance to help ensure the safety and quality of combination products. These 

activities include the following:

· Facilitating and leading the Agency’s efforts to develop and publish regulations, 

guidance documents, compliance programs, 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;

· Facilitating and leading meetings between industry and FDA regarding these 

matters; and

· Working with other Agency components to train staff, develop procedures, and 

update IT systems to enhance the efficiency and consistency of postmarket 

regulatory activities.

In addition, OCP may provide support for FDA’s CGMP facility inspections and FDA’s

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.
30

In particular, in FY 2022, OCP’s postmarket programmatic work included the following:

· Leading or supporting Centers’ development of additional guidance on CGMPs;

· Publishing a listing of alternative or streamlined mechanisms for compliance with 

combination product CGMP requirements as mandated by the Cures Act;

· Engaging with the Centers and ORA on data gathering and analysis relating to 

the tracking of combination products, the inspection of manufacturing facilities,

and their assessment of postmarket safety events;

· Supporting the training of the Agency’s postmarket staff; and

· Enhancing the Agency’s IT systems to support the work of FDA’s postmarket 

staff.

(See Section VI for a further discussion of OCP’s postmarket policy activities in FY 

2022.)

OCP’s FY 2022 product-specific actions related to the consistency and appropriateness 

of its postmarket regulatory activities are reflected in Table 26.

Table 26. Product-Specific Postmarket Regulatory Activities from FY 2017 to FY 

2022.

FY 

17

FY 

18

FY 

19

FY 

20

FY 

21

FY 

22

Postmarket 

Regulatory Activities 74 86 62 113 84 39

OCP engaged in 39 product-specific, postmarket-related 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 for facility registration and product listing. In addition, at the request of the 

Centers, OCP facilitated the Centers’ assessments of safety signal evaluations to 

determine the Agency’s response to the safety issue.

These efforts have helped improve the consistency of postmarket regulations in a 

number of ways, including the following:

· Clarifying stakeholders’ and FDA’s understanding of combination product CGMP 

requirements and inspectional approaches and
31

· Facilitating the implementation of combination products’ requirements under the 

PMSR final rule.

28

28 See 81 FR 92603 (Dec. 20, 2016), available at 

https://www.federalregister.gov/documents/2016/12/20/2016-30485/postmarketing-safety-reporting-forcombination-products.
32

V. 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., inter-Center 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).

A. 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 2022. 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). Data 

provided in the “Premarket Review Facilitation/Oversight” section of this report provide 

examples of OCP’s informal facilitation and resolution of issues related to premarket 

review.
33

VI. Policy Activities and Accomplishments

OCP’s policy activities include leading and contributing to policy initiatives important to 

the regulation of combination products. Key examples of such activities pursued in 

FY 2022 are discussed below and included in the tables to follow.

A. Supporting and Implementing Legislative Initiatives

OCP continued to participate in the development of FDA’s positions in response to 

congressional inquiries and in the development of legislative proposals. OCP also

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

implement section 3038 of the Cures Act regarding combination products. In addition, 

OCP was involved in the implementation of activities related to PDUFA VI for 

combination products (e.g., developing bridging and human factors guidance 

documents).

B. Streamlining Regulations

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

including reviewing the comments received on the proposed rule,29 to update and clarify 

the regulations in light of legislative and other policy developments. In addition, OCP 

supported rulemakings related to combination products that were led by the human 

medical product Centers, including rulemakings on (1) medical gases and (2) the 

amendment of device quality system regulations and (3) any associated adjustments to 

CGMP requirements for combination products under 21 CFR part 4.

C. Clarifying Regulatory Policies

OCP collaborated with the human medical product Centers to develop and publish 

regulations, guidance documents, notices, safety communications, and internal 

procedures. 

In FY 2022, OCP led the development and publication of a Federal Register notice on 

alternative or streamlined mechanisms for complying with CGMP requirements for 

combination products;

30 publication of this notice was mandated by the Cures Act.

29 See 83 FR 22428 (May 15, 2018), available at 

http://www.federalregister.gov/documents/2018/05/15/2018-10321/product-jurisdiction.

30 See 87 FR 56066 (Sep. 13, 2022), available at https://www.govinfo.gov/content/pkg/FR-2022-09-

13/pdf/2022-19713.pdf.
34

In addition, OCP contributed to the development and publication of additional 

documents implicating the regulation of combination products, including the following: 

· Medical Device De Novo Classification Process (final rule) (Oct. 2021);

31

· COVID-19 Public Health Emergency: Considerations for the Development of 

COVID-19-Related Sanitation Tunnels for Application of Aerosolized Antiseptics 

to Humans (final guidance document) (Feb. 2022);

32

· Certain Ophthalmic Products: Policy Regarding Compliance With 21 CFR Part 4 

Guidance for Industry (final guidance document) (March 2022);

33

· Current Good Manufacturing Practice, Certification, Postmarketing Safety 

Reporting, and Labeling Requirements for Certain Medical Gases (proposed 

rule) (May 2022);

34

· Risk Management Plans to Mitigate the Potential for Drug Shortages (draft 

guidance document) (May 2022);

35

· Patient Labeling for Human Prescription Drug and Biological Products (final 

guidance document) (July 2022);

36

· Conducting Remote Regulatory Assessments Questions and Answers (draft 

guidance document) (July 2022);

37 and

· Clinical Decision Support Software (final guidance document) (Sept. 2022).

38

31 https://www.federalregister.gov/documents/2021/10/05/2021-21677/medical-device-de-novoclassification-process.

32 https://www.federalregister.gov/documents/2023/03/13/2023-05094/guidance-documents-related-tocoronavirus-disease-2019-covid-19. Note: This guidance document is no longer in effect since the 

expiration of the COVID-19 PHE declaration.

33 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/certain-ophthalmicproducts-policy-regarding-compliance-21-cfr-part-4-guidance-industry.

34 https://www.federalregister.gov/documents/2022/05/23/2022-10458/current-good-manufacturingpractice-certification-postmarketing-safety-reporting-and-labeling.

35 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/risk-management-plansmitigate-potential-drug-shortages.

36 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/instructions-use-patientlabeling-human-prescription-drug-and-biological-products-content-and-format.

37 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/conducting-remoteregulatory-assessments-questions-and-answers.

38 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-decision-supportsoftware.
35

D. Other Policy-Related Activities

Additional policy-related activities included the following:

· Enhancing procedures and mechanisms for monitoring and enhancing 

combination products’ premarket and postmarket regulatory activities, consistent 

with section 3038 of the Cures Act;

· Conducting performance evaluations and updates of procedural and IT systems 

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

and

· Supporting implementation of the compliance program for combination product 

CGMPs.

Tables 27 through 29 identify FDA’s policy development work that continued in FY

2022; this work is categorized by topic area (i.e., jurisdiction, premarket review, 

postmarket regulation) and activity type.

Table 27. Additional Jurisdictional Regulatory Initiatives.

Type of Activity FY 2022 Activities

Developing regulations and 

guidance documents

OCP’s jurisdiction-related activities included 

participating in the following Agency rulemaking 

and guidance document initiatives:

· Led policy development on the scope and 

significance of the status of cross-labeled 

combination products; and

· Led updates to the guidance document on 

the preparation of RFDs and Pre-RFDs.

Participating in other interCenter and Agency-wide 

working groups to clarify 

issues related to product 

jurisdiction

OCP continued to enhance the efficiency and 

transparency of the RFD and Pre-RFD 

programs.
36

Table 28. Additional Premarket Review Regulatory Initiatives.

Type of Activity FY 2022 Activities

Developing regulations,

guidance documents, and 

policy documents

OCP’s premarket review-related activities 

included leading the following Agency 

rulemaking and guidance document initiatives:

· Continued to lead the development of a 

final guidance document on human factors 

studies for combination products;

· Continued to lead the development of a 

draft guidance document on the technical 

aspects of intravaginal system combination 

products;

· Continued to lead the development of a 

final guidance document on the technical 

considerations for demonstrating the 

reliability of combination product 

emergency-use injectors;

· Continued to lead the development of a 

draft guidance document on essential 

performance requirements;

· Continued to lead a working group on

insulin pump labeling;

· Continued to lead the development of a 

draft guidance document on insulin pump 

labeling;

· Continued to lead the development of an

update to a final guidance document on

the application of user fees for combination 

products; and

· Led ongoing efforts to revise the published 

draft guidance document on postmarket 

changes for combination products.

OCP participated in the development of the 

following policy documents: 

· Rulemaking on De Novo classification;

· Citizen petition responses for specific 

types of generic combination products;

· Cross-Center draft guidance document on 

considerations for what constitutes clinical 

data for user fee purposes;
37

Type of Activity FY 2022 Activities

· Cross-Center draft guidance document on 

technical considerations for container 

closures that are also device constituent 

parts; and

· International Council for Harmonisation of 

Technical Requirements for 

Pharmaceuticals for Human Use’s (ICH’s)

Q12 implementation guidance document.

Participating in other interCenter 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 following:

· Non-prescription drug availability;

· The Agency’s thinking on the regulation of 

certain software output as drug labeling;

· Application of artificial intelligence and 

machine learning in investigational, 

diagnostic and treatment settings;

· Issues such as importation of prescription 

drugs, good guidance practices, and 

enforcement policies; and

· Considerations for compounded drugs for 

use with devices.

Conducting procedural 

oversight and facilitation and 

other activities

· OCP led a working group regarding the 

monitoring and continuous improvement of 

the inter-Center consult process, including 

IT developments and enhancements;

· OCP continued to chair a cross-Center 

working group to develop procedures for 

standardizing and improving efficiency in 

the management of master files that will be 

used by more than one Center; and

· OCP led ongoing efforts to revise interCenter agreements on medical product 

Center assignment/regulatory coordination.
38

Table 29. Additional Postmarket Review Regulatory Initiatives.

Type of Activity FY 2022 Activities

Leading or participating in 

other Inter-Center and 

Agency-wide working groups 

and other activities to clarify 

issues related to combination 

products 

OCP’s postmarket review-related activities 

included participating in the following Agency 

rulemaking, guidance document, and other

initiatives:

· OCP supported the development of a final 

rule to amend 21 CFR part 820 to align 

more closely with International 

Organization for Standardization 13485 

and associated amendments to 21 CFR 

part 4.

· OCP continued to chair working groups 

relating to the PMSR requirements for 

combination products. These groups’

work focused on implementing the rule, 

monitoring the engagement between the 

Centers and OCP on postmarket 

combination product issues, and 

developing and delivering internal training.

· OCP continued to work with the Centers 

on track-and-trace programs with respect 

to combination products, including a

guidance document on the use of unique 

device identifiers, numeric drug codes, 

and serialized numeric identifiers.

· OCP continued to co-chair a committee of 

the Association for the Advancement of 

Medical Instrumentation. This 

committee’s ongoing work on combination 

products related to best manufacturing 

practices, the training of regulated entities’ 

staff on combination product regulations,

and best practices across the combination 

products’ lifecycle.

· OCP continued to participate in an 

American Society for Testing and 

Materials (ASTM) International standardsetting process to clarify terminology 

related to combination products and the 

combined use of different types of medical 

products. 
39

VIII. Additional Activities and Accomplishments

A. Information Technology Initiatives

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 2022 to improve the InterCenter Consult Request workflow and data capture system, including changes to 

better enable the requesting Center to know to which group they should send a 

consult request and features to enhance the user experience, such as a new 

component for downloading the work product provided by the consulted Center. 

· OCP implemented eight enhancement releases in FY 2022 to improve the

combination product PMSR dashboard’s functionality and user experience. This 

dashboard, to the extent feasible, integrates data on combination products from 

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

systems, and adverse event reporting systems—from all three human medical 

product Centers into a single point of reference; this integration enhances the 

efficiency and consistency of postmarket safety activities. Examples of 

enhancements in these releases included adding graphs to enable unique 

visualization capabilities, redesigning the user interface with modern elements, 

automating the connection to an existing data source, and reorganizing and 

adding content based on user feedback. 

· OCP implemented four enhancement releases for FY 2022 to improve the 

electronic system that manages the workflow and data capture system for PreRFD and RFD reviews and decisions. Examples of enhancements included

adding (1) a new capability to withdraw a previously submitted Pre-RFD or RFD, 

(2) system-generated notifications to prompt the timely review of submissions, 

(3) enhanced reporting capabilities, and (4) personalized dashboard views for 

reviewers. OCP completed a formal pilot with external volunteers of a new PreRFD and RFD electronic submission process that was aimed at improving the 

efficiency and completeness of electronic submissions. Based on feedback 

received from the pilot, updates were made to the electronic submission process, 

which is pending release for use.

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

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

OCP also engaged users through surveys, user shadowing sessions, direct 

interactions, and other means to solicit feedback and identify potential 

improvements to the IT systems. 
40

B. External Outreach

OCP engages trade associations and coalitions (e.g., the Combination Products 

Coalition, the Advanced Medical Technology Association, the Pharmaceutical Research 

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

represent the drug, device, biological product, and combination product industries. 

OCP’s discussions with these trade associations and coalitions involved FDA’s 

classification, assignment, and regulation of combination products, as well as other

related regulatory topics. These discussions have enhanced communication between 

the Agency and external stakeholders and help FDA address questions or challenges 

faced by sponsors developing combination products. 

In addition, OCP participates in national and international standards development 

organizations, including co-chairing a committee on combination products for the 

Association for Advancement of Medical Instrumentation and supporting the work of the 

International Organization for Standardization, ICH, International Medical Device 

Regulators Forum, and ASTM International. 

Further, OCP presents at various industry conferences. These conferences offer 

opportunities for Agency officials to engage with stakeholders, to clarify areas of 

stakeholder confusion, and to learn about stakeholder questions and concerns that may 

warrant investigation and, if needed, the development of policy by FDA to address those 

concerns.

In FY 2022, FDA addressed a wide range of topics about which stakeholders had 

questions, concerns, or proposals for Agency consideration. These topics included 

emerging issues in combination product regulation and the broader area of the 

combined use of separately distributed medical products; opportunities for regulatory 

convergence across jurisdictions; policies and guidance documents under development; 

rulemakings; regulatory issues for specific categories of combination products, 

particularly cross-cutting regulatory issues for combination products and combined use 

products; and stakeholder priorities for further action. 

Examples of OCP’s FY 2022 outreach activities via industry conferences are included in 

Table 30.
41

Table 30. Examples of FY 2022 Outreach Activities.

Type of Activity FY 2022 Accomplishments

Presentations and 

outreach activities

The following are examples of venues/events for which 

OCP provided presentations and/or educational outreach:

· Association for the Advancement of Medical 

Instrumentation (AAMI)/FDA/British Standards 

Institute (BSI) International Conference on Medical 

Device Standards (Oct. 2021)

· Drug Information Association (DIA) Combination 

Products Conference (Oct. 2021)

· Food and Drug Law Institute (FDLI) Combination 

Products Webinar (Dec. 2021)

· Orange County Regulatory Affairs (OCRA)/San 

Diego Regulatory Affairs Network (SDRAN)

Introduction to Combination Products Virtual Event 

(Dec. 2021)

· SMi’s Pre-Filled Syringes East Coast (Apr. 2022)

· Partnership Opportunities in Drug Delivery (PODD)

Combination Product Panel (May 2022)

· DIA Annual Conference (June 2022)

· The Organisation for Professionals in Regulatory 

Affairs (TOPRA)/CRED Drug/Device Combination 

Products Course (June 2022)

· Medtech & Pharma Platform (MPP) 2022 Annual 

Conference (Sept. 2022)
42

FY 2021 Updated Performance Detail

The table below reflects the 563 original applications classified into one of nine 

categories of combination products received in FY 2021.

Table 1. Workload by Combination Product Category Number.

Application 

Type 1 2 3 4 5 6 7 8 9 Total

Original NDA 13 20 0 1 0 0 0 0 3 37

Original BLA 1 0 10 0 0 0 0 0 2 13

Original PMA 0 0 0 4 0 0 0 0 0 4

Original 

510(k) 5 0 1 39 0 0 1 0 0 46

Original IND 14 59 43 4 4 43 8 106 9 290

Original IDE 1 0 0 24 13 0 5 2 6 51

Original HDE 0 0 0 0 0 0 0 0 0 0

Original 

ANDA 34 79 0 0 0 0 0 0 7 120

Biosimilar 

BLA 0 0 0 0 0 0 0 0 0 0

De Novo 0 0 0 2 0 0 0 0 0 2

Total 68 158 54 74 17 43 14 108 27 563

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
43

Workload by Center Lead

The pie chart to the right shows the 

number and percentage of combination 

product applications in FY 2021 by Center 

lead, as of September 30, 2022.

CBER 

39 (7%)

CDER 

431

(77%)

CDRH

93 

(16%)

Combination Product 

Applications (n = 563)
FY

This report was prepared by FDA's Office of Combination Products in 

collaboration with the Office of Planning, Evaluation, and Risk 

Management in the Office of the Commissioner; the Center for 

Biologics Evaluation and Research; the Center for Drug Evaluation and 

Research; and the Center for Devices and Radiological Health. For 

further information, please contact:

Office of Planning, Evaluation, and Risk Management

Office of the Commissioner

U.S. Food and Drug Administration

10903 New Hampshire Ave.

Silver Spring, MD 20993-0002

Phone: 301-796-4850

E-mail: OPERM_ADMIN_Team@fda.hhs.gov

This report is available on FDA’s home page at https://www.fda.gov/

and on OCP’s home page at https://www.fda.gov/combinationproducts.