FY 2018 

PERFORMANCE REPORT

TO CONGRESS

for the

Office of 

Combination Products

as required by the

Medical Device User Fee and

Modernization Act of 2002
Commissioner’s Report

I am pleased to submit the Food and Drug Administration’s (FDA or the Agency) Fiscal Year 

(FY) 2018 Annual Report to Congress for the Office of Combination Products (OCP). This 

report includes data from the 15th full year since OCP was established, as mandated by the 

Medical Device User Fee and Modernization Act of 2002, P.L. 107-250 (MDUFMA), 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 between FDA’s human medical product Centers, which are 

made up of 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). 

Combination products involve constituent parts that would normally be regulated under different 

types of regulatory authorities, and frequently by different FDA Centers, which can raise 

regulatory, policy, and review management challenges. Differences relating to the normal

regulatory pathways and considerations for each type of constituent part (drug, device, 

biological product) can impact the regulatory processes for all aspects of product development 

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

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

fees, and post-approval modifications.

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

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

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

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

effective premarket review, and ensure the consistent and appropriate postmarket regulation of 

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

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

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

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

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

FDA reviewers in understanding the complexities of this regulatory area. 

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

regulation of combination products. 

 Stephen M. Hahn, M.D.

 Commissioner of Food and Drugs
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Executive Summary

FDA established the Office of Combination Products (OCP) on December 24, 2002, as required 

by the Medical Device User Fee and Modernization Act of 2002 (Pub. L. 107-250). The 

statutory mission of OCP is to ensure the prompt assignment of combination products (for drugdevice, biologic-device, drug-biologic, or drug-device-biologic products) to Food and Drug 

Administration (FDA) Centers; the timely, effective, and aligned premarket review of such 

applications; and the consistent and appropriate postmarket regulation of like products subject 

to the same statutory requirements to the extent permitted by law. 

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

and accomplishments during fiscal year (FY) 2018 (i.e., from October 1, 2017, to September 30, 

2018). OCP’s activities and performance for FY 2018 that are highlighted in this report include

the following: 

1. Prompt Assignment of Combination Products. In FY 2018, OCP continued to clarify 

the jurisdictional assignment of combination products and to provide prompt Request for 

Designation (RFD) decisions. OCP issued eight 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 

Center assessments for 82 separate Pre-RFD submissions. OCP issued a final 

guidance in February 2018,

1 on its preliminary product classification assessment (PreRFD) process.

2. Timely and Effective Combination Product Review. In FY 2018, OCP received 321 

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

the timely and effective review of combination products. This number of requests is a 39 

percent decrease from the 525 requests received in FY 2017. OCP also fully 

implemented a revised inter-Center consult process that was piloted in FY 2017. This 

new process enhanced the efficiency, coordination, and consistency of the review of 

combination products. The corresponding revised staff manual guide (i.e., SMG 4101) 

was published in June 2018. Other OCP activities relating to premarket review included 

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

regulatory issues, clarify regulatory standards, address challenging categories of 

products, identify and resolve specific product issues, update the premarket review 

process, and address developmental considerations for combination products.

FDA received 498 original premarket applications for combination products in FY 

2018. This number of applications reflects a 14 percent decrease from the 566

applications of the types reported in FY 2017.2

 Inter-Center consulting reviews for 

combination products increased to 1,445 for FY 2018 from 1,419 in FY 2017. 

 

1 This final guidance is available at https://www.fda.gov/media/102706/download. 

2 The FY 2017 numbers were changed to reflect updates to data presented in the FY 2017 OCP performance report. 

The updated data for FY 2017 is located in Appendix A of the FY 2018 performance report.
a. Examples of combination product types can be found at the OCP website at

www.fda.gov/CombinationProducts/default.htm.

3. Consistent and Appropriate Postmarket Regulation. In FY 2018, OCP provided 

clarification and support for 86 separate postmarket matters. OCP continued to chair 

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

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

FDA (1) published a draft guidance in March 20183 on the implementation of its 

December 2016 final rule on PMSR for combination products and (2) issued a proposed 

list of alternative or streamlined mechanisms for complying with CGMPs in June 20184 as 

required by the 21st Century Cures Act (Cures Act) (Pub. L. 114-255). 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. The cross-cutting decisional 

Combination Products Policy Council, consisting of senior leaders from all three human 

medical product Centers, the Office of Medical Products and Tobacco, the Office of 

Special Medical Programs, and OCP, continued to provide direction regarding complex 

policy and procedural questions for combination products. Topics addressed included

the implementation of section 3038 of the Cures Act, as well as human factors, the interCenter consult process, the availability of premarket pathways for combination products, 

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

considerations for cross-labeled and other separately distributed medical products 

intended for combined use. OCP also continued to conduct external outreach activities 

through a variety of educational and informational presentations to national and 

international audiences. These activities were intended to foster greater efficiency of the 

combination product development and premarket review process by enhancing 

understanding of the complex regulatory and scientific issues that often arise regarding 

combination products. 

 

3 This draft guidance is available at https://www.regulations.gov/document?D=FDA-2008-N-0424-0023. 

4 83 FR 27609 (June 13, 2018), available at https://www.federalregister.gov/documents/2018/06/13/2018-

12634/alternative-or-streamlined-mechanisms-for-complying-with-the-current-good-manufacturing-practice. 
Table of Contents

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

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

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

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

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

Requirement Workload Trends: FY 2013 to FY 2018 ...................................... 4

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

Internal Center-Requested Classification and Assignment Consultations......... 9

Additional Classification and Assignment Activities .......................................... 9

Accomplishments ...........................................................................................10

Combination Product Premarket Review ......................................11

Number and Types of Combination Products Submitted for Review...............11

Requirement Workload Trends: FY 2013 to FY 2018 .....................................12

Timeliness in Days for the Review of Combination Products ..........................15

FY 2017 and FY 2018 Review Performance ..................................................17

Premarket Review Facilitation/Assistance...................................................18

Combination Product Postmarket Activities................................. 20

Effective Resolution of Review Disputes ......................................22

Percentage of Combination Products Reviewed for which a Dispute Resolution was 

Requested......................................................................................................22

Policy Activities and Accomplishments........................................23

Regulatory Initiatives ......................................................................................23

Additional Premarket Review Regulatory Initiatives ....................................25

Additional Postmarket Review Regulatory Initiatives...................................26

Additional Activities and Accomplishments................................. 27

Information Technology..................................................................................27

External Outreach ..........................................................................................27

Appendix............................................................................................29

Appendix A: FY 2017 Updated Performance Detail.......................................29
Abbreviations

510(k) – Premarket Notification

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

FDA – Food and Drug Administration

FY – Fiscal Year (October 1 to September 30)

GDUFA – Generic Drug User Fee Act

HDE – Humanitarian Device Exemption

IDE – Investigational Device Exemption

IND – Investigational New Drug

ISO – International Organization for Standardization

MDUFA – Medical Device User Fee Amendments 

MDUFMA – Medical Device User Fee and Modernization Act 

NDA – New Drug Application

NSE – Not Substantially Equivalent

OCC – Office of the Chief Counsel

OCP – Office of Combination Products

PDUFA – Prescription Drug User Fee Act

PMA – Premarket Approval Application

PMC – Postmarketing Commitment

PMR – Postmarketing Requirement

Pre-RFD – Pre-Request for Designation

RFD – Request for Designation

SE – Substantially Equivalent
1 FY 2018 OCP Performance Report

Introduction

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

107-250) was signed into law. Among other things, MDUFMA required the Food and Drug 

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

combination products to agency centers, the timely and effective premarket review of such 

products, and consistent and appropriate postmarket regulation of like products to the extent 

permitted by law.” In response, FDA established the Office of Combination Products (OCP) 

within the Office of the Commissioner. On December 13, 2016, the 21st Century Cures Act 

(Cures Act) (Pub. L. 114-255) was signed into law. Among other things, the Cures Act clarified 

and expanded the duties of OCP to include ensuring the alignment of 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 OCP website at 

www.fda.gov/CombinationProducts/default.htm. 

Description of Combination Products

21 CFR 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.

Some combination products have the potential to provide enhanced therapeutic advantages 

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

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

Combination products may include drug delivery systems, gene therapy systems, personalized 
2 FY 2018 OCP Performance Report

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

nanotechnology, and other innovative products. 

Statutorily Mandated Functions of OCP

 

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

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

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

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

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

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

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

Specifically, section 503(g)(8) of the Federal Food, Drug, and Cosmetic Act requires OCP to, 

among other things, complete the following functions: 

(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 Agency feedback to the product sponsor 

and by coordinating reviews involving more than one Center;

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

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

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

and

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

practices specific to the assignment of combination products.

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

raised by FDA 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 combination products regulation. 

In addition, OCP has responsibility for FDA action on every Request for Designation (RFD) 

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

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

combination product, or a determination of its Center assignment or both.
3 FY 2018 OCP Performance Report

Performance Presented in This Report

This report presents fiscal year (FY) 2018 OCP activities and accomplishments, including key 

measures that should be made public. These reportable measures support the mandated 

functions of OCP. Specifically, this report presents information and data on OCP activities 

related to the following:5

• 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, 2018. 

 

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

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

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

adjustments may be appropriate for subsequent reports. 
4 FY 2018 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 primary jurisdiction for combination 

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

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

a statutory 60-day deadline.6

 OCP also provides responses to Pre-RFD requests for assistance 

regarding product classification and assignment.7

Requirement Workload Trends: FY 2013 to FY 2018 

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

assignments) in FY 2018 is compared to the previous 5-year average. The total number of RFD 

determinations in FY 2018 remained the same compared to FY 2017. However, the individual 

numbers of combination product and non-combination product determinations varied compared 

to their respective 5-year average. Specifically, the RFD determinations for combination 

products increased by 14 percent over the previous 5-year average; this is in contrast to the 

RFD determinations for non-combination products for which none were issued in FY 2018.

RFD Determinations 8

RFD Submissions FY 13 FY 14 FY 15 FY 16 FY 17 FY 18

FY 13 to 

FY 17

5-Year 

Average

FY 18 

Compared 

to 5-Year 

Average

Total RFD Combination 

Product Classifications/ 

Assignments 

17 8 2 2 5 8 7 +14% 

Total RFD Non-Combination 

Product Classifications/ 

Assignments

14 9 7 2 3 0 7 -100% 

 

6 OCP also provides assistance to product sponsors regarding preparation of RFDs and works with sponsors who 

disagree with FDA’s PMOA determination on potential studies addressing PMOA matters (see 21 U.S.C. 

353(g)(1)(F)). 

7 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 FY 2018 Pre-RFD submissions (including the timeliness of OCP responses) is 

provided in the section below titled Pre-RFD Workload Performance. 

8 Over the reported 5-year time frame, the 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 OCP Pre-RFD Workload 

Performance for more information.
5 FY 2018 OCP Performance Report

OCP received 56 RFD submissions in FY 2018.9

 Of these submissions, decisions were issued 

for 8 of them (14 percent), 44 of them were found to have insufficient information for filing (79 

percent), 3 of them were pending at the end of FY 2018 (5 percent),

10 and 1 of them was 

withdrawn by the product sponsor prior to filing (2 percent). OCP also issued one response to a 

Request for Reconsideration of one of those RFD decisions by the 15-day review period as 

specified by regulations. 

The total number of RFD combination 

product classifications and assignments 

issued in FY 2018 increased by 3 

compared to FY 2017. 

The total number of RFD non-combination 

product classifications and assignments 

issued in FY 2018 decreased by 3 compared 

to FY 2017. 

 

9 Of these 56 submissions, all were received in 2018, and none were carried over from the prior fiscal year.

10 These three submissions were undergoing review at the end of FY 2018 and were carried over to FY 2019.

FY 13 FY 14 FY 15 FY 16 FY 17 FY 18

Total 17 8 2 2 5 8

CBER 2 1 0 0 0 1

CDER 9 5 1 1 4 6

CDRH 6 2 1 1 1 1

0

5

10

15

20

25

30

35

40

Number of Requests

Combination Product Assignment Requests

FY 13 FY 14 FY 15 FY 16 FY 17 FY 18

Total 14 9 7 2 3 0

CBER 5 2 4 0 1 0

CDER 6 4 1 2 0 0

CDRH 3 3 2 0 2 0

0

5

10

15

20

Number of Requests

Non-Combination Product Assignment 

Requests
6 FY 2018 OCP Performance Report

In FY 2018, the 8 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 59 days. 

The following tables provide timeliness data by product type of the issued RFD decision. 

Timeliness of Combination Product 

Determinations

Determination

Product

Assignments

Issued*

Percent

On Time*

Drug-Device 7 100%

Drug-Biologic 0 NA

Device-Biologic 1 100%

Drug-DeviceBiologic 0 NA

Total 8 100%

* Does not include request for reconsideration responses, 

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

21 CFR 3.8. One request for reconsideration was submitted 

for a combination product in FY 2018.

Timeliness of Non-Combination Product 

Determinations

Determination

Product

Assignments

Issued*

Percent

On Time*

Drug 0 NA

Biologic 0 NA

Device 0 NA

Total 0 NA

* 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 2018. 
7 FY 2018 OCP Performance Report

Pre-RFD Workload Performance 

In addition to responding to RFDs, OCP provided preliminary feedback/assessments in 

response to Pre-RFD submissions for product classification and jurisdictional assignment. The 

Pre-RFD process may be preferable in some circumstances to the more formal RFD process. 

For example, Pre-RFD submissions allow for more discussions (e.g., teleconferences) between 

FDA and a sponsor if questions arise during review. In the tables below, OCP Pre-RFD 

submission review workloads in FY 2018 are provided. FY 2018 is the second full year of the 

“formalized” Pre-RFD program.11 As such, available data allowing for a multi-year comparison 

(e.g., a comparison to 5-year averages) are not yet available. However, this year-to-year 

comparison data will be provided in future reports as they become available.

OCP Pre-RFD Submission Assessments

FY 17 FY 18 

Combination Product Assessments 44 48

Non-Combination Product 

Assessments 34 28

Unclassified Assessments* - 6 

Total Pre-RFD Assessments 78 82

* Six Pre-RFD assessments did not result in a 

classification as a drug, device, biological product, or 

combination product, and/or a Center assignment. For 

instance, products that fell under this category may (1) 

not have met the criteria for regulation solely under 

section 361 of the Public Health Service Act and 21 

CFR part 1271 or (2) have been for submissions in 

which a sponsor may have pursued only a product 

assignment and not a classification. 

 

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 Center-requested consultations 

(i.e., product classification and jurisdictional requests that originate with the FDA Centers and not with product 

sponsors). However, Pre-RFD 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 2018 OCP Performance Report

Of the 82 total FY 2018 Pre-RFD assessments, 98 percent were issued by OCP’s internally 

established 60-day goal, which started on the date of receiving sufficient information to provide 

requested feedback12 (see the following tables). In FY 2018, the 60-day review goal was 

missed for 2 submissions out of 82. The average review time for Pre-RFD assessments was 37 

days, with a median review time of 54 days. The following tables show Pre-RFD assessments

for combination products and non-combination products based on the product’s classification 

and the Center assignment.

Number of Combination Product Pre-RFD Assessments

Classification Assignments

Issued

Percent

Issued in 60 

Days

Drug-Device 40 100%

Drug-Biologic 0 NA

Device-Biologic 5 100%

Drug-DeviceBiologic 3 100%

Total 48 100%

Number of Combination Product Pre-RFD Assessments by Center Assignment

Center 

Assignment

Consultations

Issued

CDER 35

CBER 4 

CDRH 9 

Total 48

Number of Non-Combination Product Pre-RFD Assessments

Classification Assignments

Issued

Percent

Issued in 60 

Days

Drug 9 89%

Biologic 5 100%

Device 14 93%

Total 28 93%

 

12 OCP does not have a mandated review time frame for Pre-RFD assessments. However, OCP attempts to review 

Pre-RFD assessments within the same time frame as RFD submissions (i.e., 60 days).
9 FY 2018 OCP Performance Report

Number of Non-Combination Product Pre-RFD Assessments by Center Assignment

Center 

Assignment

Consultations

Issued

CDER 9 

CBER 6 

CDRH 13

Total 28

Internal Center-Requested Classification and Assignment Consultations 

In addition to responding to RFDs and Pre-RFDs submitted by industry/sponsors, OCP provided 

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

response to requests from Centers in relation to premarket submissions. Centers may consult

OCP for assistance in determining if the product submitted to a Center for review is 

appropriately assigned to that Center, whether the sponsor would need to be referred to OCP 

for a classification or assignment determination, or both. The number of the consultations 

provided by OCP is presented in the table below. As with the Pre-RFD data presented above, 

FDA intends to provide, in future reports, metrics for multiple fiscal years, as such data become 

available. 

Center-Requested Classification and Assignment Consultations

Center 

Assignment FY 17 FY 18

CDER 29 31

CBER 3 3 

CDRH 16 14

Unassigned13 0 2 

Total 48 50

Additional Classification and Assignment Activities

This category reports on all other activities not falling within the classification and assignment 

activities reported above. Examples of this category of activity include responding to questions 

about process (e.g., how to prepare an RFD or Pre-RFD) and providing feedback to sponsors 

regarding the design of studies (e.g., to evaluate PMOAs). This category also includes 

responses to individual email queries and meetings and teleconferences that OCP holds with 

sponsors. 

 

13 The term unassigned indicates that a determination/assessment of Center assignment was not made. This may be 

the case, for example, if the question before OCP concerns solely product classification.
10 FY 2018 OCP Performance Report

Additional Number of Product Classification and Assignment Activities

FY 17 FY 18

Jurisdiction/Classification Issues 528 529

Accomplishments

Type of Activity FY 2018 Accomplishments

Issuing required RFD assignments 

within 60 days

OCP issued all RFD assignments by the statutory 60-day 

determination deadline.

Clarifying standards for product 

classification and preparing guidance 

on this issue

In late FY 2017, OCP published a final guidance on the 

classification of drugs and devices and additional issues related 

to product classification.14 OCP continued to chair a working 

group, including staff from CDER, CDRH, CBER, and the Office 

of Chief Counsel (OCC), to clarify interpretive standards; to 

address the classification and assignment of challenging 

categories of products; to continue pursuing and supporting 

related policy initiatives, including the issuance of a final 

guidance on regulatory considerations for human cells, tissues, 

and tissue-based products (including classification);15 and to 

clarify standards for cross-labeled combination product status.

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. OCP 

continued to provide training to review staff, including personnel 

from CBER, CDER, and CDRH, as well as Office of Regulatory 

Affairs inspectors, on product classification and assignment.

See also the discussion of the issuance of a guidance on the 

Pre-RFD program and classification of products and other policy 

activities relating to product classification and assignment under 

Policy Activities and Accomplishments.

 

14 This guidance is available at https://www.fda.gov/media/80384/download. 

15 This guidance is available at https://www.fda.gov/media/124138/download. 
11 FY 2018 OCP Performance Report

Combination Product Premarket Review 

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

combination products, which includes overseeing the timeliness of reviews and aligning

feedback by coordinating reviews involving more than one Center. 

In 2002, FDA established policies and procedures for FDA staff to follow when requesting, 

receiving, handling, processing, and tracking formal reviews of combination products, devices, 

drugs, and biological products. This policy was formally incorporated into the FDA Staff Manual 

Guide, Agency Program Procedures, Volume IV, effective June 18, 2004.

In FY 2017, in light of feedback from stakeholders and internal FDA staff regarding the 

consistency, efficiency, and coordination within FDA of premarket reviews for combination 

products, FDA piloted a revised inter-Center consultative process to ensure that consultations 

occur as appropriate, improve the early identification of the appropriate inter-Center review 

team, enhance the efficiency of consult request issuance and the clarity of questions asked, and 

better ensure FDA’s responsiveness and documentation of completed consults. Based on the 

results of this pilot, an updated process has been implemented and incorporated into the 

appropriate FDA Staff Manual Guide in FY 2018.

Number and Types of Combination Products Submitted for Review

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

The following information refers to FDA performance data presented in this subsection.

• Data on the number and types of combination products submitted for review for FY 2018 

by CBER, CDER, and CDRH (includes submissions filed or received in FY 2018). 

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

products, the Prescription Drug User Fee Act (PDUFA VI) goals were referenced for 

priority and standard new drug applications (NDAs) and applicable biologics license 

applications (BLAs), the Generic Drug User Fee Act (GDUFA II) goals were referenced 

for 2018 goals for abbreviated new drug applications (ANDAs), and the Biosimilar User 

Fee Act (BsUFA II) goals were referenced for 2018 goals for biosimilar BLAs. For 

CBER-led or CDRH-led combination products, the Medical Device User Fee 

Amendments (MDUFA IV) goals were referenced for expedited and original premarket 

approval applications (PMAs), premarket notifications (510(k)s), De Novo classification 

requests (De Novos), and device BLAs.

• Some product review goals, such as for NDAs, were defined by the number of months to 

review the product. Because of the differences in the numbers of days in each month 

(28 to 31), 10 months represented 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 represented

a range from 182 days (such as February 15 to August 15) to 184 days (such as July 15 

to January 15).
12 FY 2018 OCP Performance Report

• Median review time was based on FDA first cycle review performance for PDUFA VI 

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

decision review time. Actual review time was used when only one action was measured.

Requirement Workload Trends: FY 2013 to FY 2018 

FY 2018 Submission Review Workloads

Submission/Request FY 13 FY 14 FY 15 FY 16* FY 1716 FY 18 

Total Combination Products 

(by Center) Submitted for 

Review

313 317 341 330 566 498 

* FY 2016 numbers were changed to reflect updates to data presented in the FY 2016 OCP Performance Report.

The total number of combination products submitted for review decreased slightly in FY 2018. 

Of all combination product submissions, 68 percent were received by CDER, 22 percent were 

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

 

16 Reported FY 2017 and FY 2018 data include additional submission types, i.e., abbreviated new drug applications 

(ANDAs) and De Novo classification (De Novos) requests, that were not previously reported in past years, and also 

track user fee performance for biosimilar products separately from other biological products. FDA has made these 

changes in light of submission trends and clarification provided by the Cures Act regarding availability of premarket 

pathways for combination products. See Appendix A for updated FY 2017 data. As such the data shown for FY 2018 

are not directly comparable to the past years shown in this table. 

FY

13

FY

14

FY

15

FY

16

FY

17

FY

18

Series5

Total 313 317 341 330 566 498

CDRH 140 126 129 95 138 107

CDER 136 147 175 199 375 340

CBER 37 44 37 36 53 51

0

200

400

600

800

1000

1200

1400

Number of Submissions

Combination Product Application 

Submissions
13 FY 2018 OCP Performance Report

The table below presents the 498 original applications for combination products received in FY 

2018, broken down by the identified ten application types and by the product’s initial 

classification into one of nine categories of combination product.17 The same table reflecting 

applications received in FY 2017 is updated in Appendix A to reflect corrections and actions as 

of September 30, 2018. The majority of the applications (47 percent) received in FY 2018 were 

original investigational new drug (IND) applications, followed by ANDAs (22 percent). Also, the 

most common combination product category was the pre-filled drug delivery device/system (23 

percent).

Workload by Combination Product Category Number

Application 

Type 1 2 3 4 5 6 7 8 9 Totals

Original NDAs 2 18 0 0 0 0 2 0 0 22

Original BLAs 1 0 5 0 0 1 0 0 0 7

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

Original 

510(k)s 7 1 0 53 1 1 2 0 8 73

Original INDs 19 29 34 4 6 48 6 81 6 233

Original IDEs 6 0 0 15 3 0 4 3 15 46

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

ANDAs 46 65 0 0 0 0 0 0 0 111

Biosimilar

BLAs 0 0 1 0 0 0 0 0 0 1 

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

Total 81 115 41 74 10 50 14 84 29 498

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

 

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

to reflect corrections and subsequent actions that may have informed the classification status, such as the ultimate 

status of products initially placed in category 8 (for certain possible combination products). 
14 FY 2018 OCP Performance Report

Inter-Center Consultation Requests

The total number of inter-Center consultation requests related to combination products 

increased for FY 2018 to the highest number in the past 6 years. The number of inter-Center

consultation requests in FY 2018 (1,445) increased by 36 percent as compared to the previous 

5-year average of 1,064.

In the table below, the total review workload for inter-Center consultation requests in FY 2018 is

compared to the previous 5-year averages. 

FY 2018 Inter-Center Consult Workloads

Submission/Request FY 13 FY 14 FY 15 FY 16 FY 17 FY 18 

FY 13 to 

FY 17 

5-Year 

Average

FY 18 

Compared 

to 5-Year 

Average

Total Inter-Center Consult 

Requests 828 1,013 932 1,130 1,419 1,445 1,064 + 36%

FY

13

FY

14

FY

15

FY

16

FY

17

FY

18

Total 828 1,013 932 1,130 1,419 1,445

CBER 31 48 53 9 105 118

CDER 506 643 499 793 881 867

CDRH 291 322 380 328 433 460

0

200

400

600

800

1000

1200

1400

1600

Number of Requests

Inter-Center Consultation Requests by 

Lead/Reviewing Center
15 FY 2018 OCP Performance Report

In the table below, the number of Inter-Center consult requests during FY 2018 is broken down 

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

Center). 

Number of Premarket Review Inter-Center Consults for Combination Products by Lead and 

Consulted Centers 

Lead Center

Consulted Center

CBER CDER CDRH Number of 

Consults

CBER -- 27 91 118

CDER 24 -- 843 867

CDRH 5 455 -- 460

Total 29 482 934 1,445

Timeliness in Days for the Review of Combination Products

FDA is required to report the timeliness in review time for combination products. The table 

below summarizes the review type and review performance target for original NDAs, ANDAs, 

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

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

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

portion of premarket applications that will be reviewed within a specified time frame. 

Performance goals apply to only 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 percent to 90 percent and vary by year. 

• For MDUFA IV performance goals, refer to

https://www.fda.gov/media/102699/download. 

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

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

• For BsUFA II performance goals, refer to https://www.fda.gov/media/100573/download. 
16 FY 2018 OCP Performance Report

Performance Goals for Original Applications†

User Fee Act 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

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

fiscal year receipt cohort. This methodology calculates performance information for 

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

or approved the submissions. This section updates FDA’s review performance on the FY 2017 

combination product submissions and presents FDA’s review performance on the FY 2018 

combination product submissions through September 30, 2018. 
17 FY 2018 OCP Performance Report

FY 2017 and FY 2018 Review Performance

The table below shows final FY 2017 review goal performance. 

Original 

Application Type

Review

Type

Review 

Within

Number of 

Combination 

Products

Median or 

Actual Review 

Time (Days)

Range of 

Review Time

(Days)

NDAs Priority 6 months 4 184 182 to 184

NDAs Standard 10 months 30* 304 276 to 365

BLAs Priority 6 months 4* 240 239 to 240

BLAs Standard 10 months 5* 363 363

Expedited and 

Original PMAs Standard 180 or 320 days† 9* 179 170 to 180

510(k)s Standard 90 days 78* 81 15 to 220

Biosimilar BLAs Standard 10 months 7* 302 302

ANDAs Standard 10 months 67* 301 267 to 316

De Novos Standard N/A‡ 1 126 126

* Included in this count are NDAs, ANDAs, BLAs, PMAs, and 510(k)s that are pending filing because the assumption is that 

they will go on to be filed. These are preliminary numbers that may change if the reported filed figures differ from the receipt 

figures.

† These figures represent a review occurring within 180 days for decisions without advisory committee input and a review 

occurring within 320 days for decisions with advisory committee input. 

‡ De Novo requests did not have an associated performance goal in FY 17.

The table below shows preliminary FY 2018 review goal performance through September 30, 

2018. 

 

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 5 182 12 to 333

NDAs Standard 10 months 17 183.5 60 to 306

BLAs Priority 6 months 3 244 214 to 333

BLAs Standard 10 months 4 277 277

Expedited and 

Original PMAs Standard 180 or 320 days 3 179 170 to 180

510(k)s Standard 90 days 73 84.5 45 to 90

Biosimilar BLAs Standard 10 months 1 361 361

ANDAs Standard 10 months 111 300 227 to 348

De Novos Standard 150 days 2 118 84 to 151
18 FY 2018 OCP Performance Report

Premarket Review Facilitation/Assistance

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

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

delineate regulatory pathways for the development of combination products and expeditiously

review premarket submissions for these products. Responding to requests from both industry 

and FDA review staff, OCP provides guidance on regulatory challenges unique to combination 

products. OCP also serves as a resource for FDA staff (1) on the appropriate use and 

interpretation of combination product categorization for premarket submissions and (2) in 

determining the correct combination product categories for data reporting purposes. Finally, 

OCP leads or participates in meetings and discussions to ensure efficient, effective 

communication between sponsors and FDA review staff. The number of OCP FY 2018

documented premarket review facilitation and assistance figures are presented below.

Number of OCP Documented Premarket Activities

FY 13 FY 14 FY 15 FY 16 FY 17 FY 18 

FY 13 to 

FY 17 

5-Year 

Average

FY 18 

Compared 

to 5-Year 

Average

Premarket Review 

Issues 157 402 225 266 525 321 315 + 2%

Number of OCP Documented Premarket Activities

FY 13 FY 14 FY 15 FY 16 FY 17 FY 18 

FY 13 to 

FY 17 

5-Year 

Average

FY 18 

Compared 

to 5-Year 

Average

Premarket Review 

Issues 157 402 225 266 525 321 315 + 2%

OCP received 321 requests for product-specific assistance from sponsors, the responses to 

which contributed to ensuring the timely, effective, and aligned review of combination products. 

Notably, OCP addressed issues such as the following: 

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

(e.g., emergency use products and complex generic combination products that include 

devices) 

• Alignment of preclinical and biocompatibility data requests

• Review of combination products for rare disease populations

• Alignment of potential clinical hold review assessments

• Accuracy, consistency, and clarity of labeling of separately distributed constituent parts
19 FY 2018 OCP Performance Report

• Alignment of warning letter considerations with ongoing developmental considerations 

for combination products 

• Ongoing development considerations of combination products that incorporate mobile 

communication technologies

• In addition, OCP oversees inter-Center consults by facilitating coordination among 

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

timely manner and meet applicable user fee timelines). Specifically, OCP tracks and 

monitors all ongoing inter-Center consult requests; clarifies internal operating 

procedures, roles, and responsibilities; identifies consulting divisions and contacts; 

clarifies due dates and completion status; facilitates access to review documents; and 

resolves other barriers to timely completion of consults. OCP periodically reviews interCenter consult data requests. OCP also conducts additional assessments, as needed, 

to ensure that the inter-Center consult request process supports the timely, consistent, 

and effective review of combination products. 

• OCP provides assistance to the FDA Centers and industry regarding regulatory and 

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

combination products. For example, OCP responded to external industry requests to 

host cross-Center early product-specific development discussions on the implications of 

the Agency’s 21 CFR part 15 hearing for devices referencing drugs.18 Detailed 

accomplishments during FY 2018 are presented in the table below.

Type of Activity FY 2018 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

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

pump infusion systems) 

• Medical imaging drugs with photodynamic device activating and 

imaging systems

• Facilitation of premarket 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 

• Ongoing regulatory considerations for a monograph drug for use with 

a device constituent part or for a Class I device for use with a drug

• Unique device identifiers and standardized numerical identification

• Alignment of IND and IDE review requirements for combination 

products

 

18 See 82 FR 44803 (September 26, 2017). 
20 FY 2018 OCP Performance Report

Combination Product Postmarket Activities 

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

combination products, and FDA is required to describe any improvements in the consistency of 

postmarket regulation of combination products. 

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

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

combination products. The compliance-related and postmarket activities include (1) leading 

Agency efforts to develop and publish regulations and to issue guidance for postmarket safety 

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

Accomplishments section below), (2) coordinating and overseeing FDA actions relating to novel 

and complex postmarket safety issues and CGMP compliance questions, and (3) facilitating and 

leading meetings between industry and FDA regarding these matters. For example, OCP 

provides support to FDA field inspectors on CGMP facility inspection issues and on the seizure 

of products at ports of entry to stop adulterated/misbranded products from entering the United 

States, assists Agency responses to product defect issues, and provides assistance on 

enforcement issues, including the development of compliance and enforcement action 

communications such as warning letters. 

OCP’s FY 2018 accomplishments related to the consistency and appropriateness of postmarket 

regulation are included below (see also the Policy Activities and Accomplishments section 

below). 

Documented Product-Specific Postmarket Regulatory Activities

FY 13 FY 14 FY 15 FY 16 FY 17 FY 18

FY 13to 

FY 17 

5-Year 

Average

FY 18 

Compared 

to 5-Year 

Average

Postmarket Regulatory

Activities 57 110 71 50 74 86 72 +19%

OCP addressed 86 product-specific, postmarket-related matters involving such issues as the 

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

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

requirements for registration and listing. This represents a 19 percent increase in the number of 

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

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

the Agency’s response approach.

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

ways, including the following: 

• Enhancing coordination among Agency components in support of CGMP inspectional 

and compliance policies and practices
21 FY 2018 OCP Performance Report

• Clarifying stakeholder and FDA understanding of CGMP obligations (see also the final 

guidance mentioned in the Policy Activities and Accomplishments section below)

• Clarifying stakeholder and FDA understanding of PMSR requirements (see also the final 

rule mentioned in the Policy Activities and Accomplishments section below)

• Aligning the assessment of postmarket safety signals and risk assessments
22 FY 2018 OCP Performance Report

Effective Resolution of Review Disputes

When requests are received, OCP is required to resolve disputes regarding the timeliness of the 

premarket review of a combination product. OCP facilitates communications between sponsors 

and FDA review staff to identify, clarify, and resolve specific concerns associated with review 

timeliness. The facilitation of issues helps prevent the need for a more formal dispute 

resolution.

In addition to disputes related to timeliness, OCP may also receive requests for dispute 

resolution and/or mediation for other review issues (e.g., inter-Center review dispute resolution 

or requests by product sponsors for assistance in understanding a review division’s intent 

regarding issued decisions).

Percentage of Combination Products Reviewed for which a Dispute 

Resolution was Requested 

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

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

sponsor.19 FDA received no requests for dispute resolution in FY 2018. Therefore, the 

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

combination product submissions reported in the Product Premarket Review section of this 

report). The Timely and Effective Premarket Review section of this report provides examples of 

FDA’s informal facilitation and resolution of issues related to premarket review.

 

19 This reporting requirement was established by the Cures Act and replaces the prior requirement to report on the 

timeliness in days of dispute resolutions regarding combination products.
23 FY 2018 OCP Performance Report

Policy Activities and Accomplishments

Regulatory Initiatives

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

combination products. Examples of such activities pursued in FY 2018 are discussed in this 

section (and included in the following tables).

Supporting Legislative Initiatives

OCP participated in development of FDA 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 issuance of new rules and guidance documents; and the enhancement of 

standard operating procedures, information technology, staff training, and outreach. OCP also 

participated in the implementation of section 706 of the FDA Reauthorization Act of 2017 (Pub. 

L 115-52). 

Streamlining Regulations 

OCP published a proposed rule to amend FDA’s jurisdictional regulations in 21 CFR part 3, as 

well as to update and clarify these regulations in light of legislative and other policy 

developments.20

Providing Clarifying Guidances 

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

guidance documents:

• Draft guidance on PMSR for combination products21

• Final guidance on the Pre-RFD program22

Completing Other Policy Activities

OCP completed additional policy activities, including the following: 

 

20 83 FR 22428 (May 15, 2018), available at https://www.govinfo.gov/content/pkg/FR-2018-05-15/pdf/2018-10321.pdf. 

21 The final guidance which published in 2019 is available at https://www.fda.gov/media/111788/download. 

22 This final guidance is available at https://www.fda.gov/RegulatoryInformation/Guidances/ucm534661.htm. 
24 FY 2018 OCP Performance Report

• Issuance of a staff manual guide (i.e., SMG 4103) on FDA’s inter-component 

coordination for combination product review23

• Issuance of a Cures Act-mandated notice of proposed alternative and streamlined 

approaches to CGMP compliance24

• Initiation of an evaluation of assessment procedures to monitor and enhance 

combination product regulatory activities in accordance with the Cures Act mandates for 

OCP

• Initiation of an evaluation of procedural and information technology measures to enable 

implementation of a final PMSR rule for combination products

Additional Classification and Assignment Regulatory Initiatives

Type of Activity FY 2018 Accomplishments

Developing regulations and guidance

Additional OCP classification and assignment-related activities 

included participating in the following Agency rulemaking and 

guidance initiatives:

• Rule on the regulatory status of wound care products

• Rulemaking on the meaning of protein in the definition of 

biological product in the Public Health Service Act (Pub. 

L. 78-410)25

• Final guidance on minimal manipulation and homologous 

use for human cells, tissues, and cellular and tissuebased products 26

Participating in other inter-Center and 

Agency-wide working groups to clarify 

issues related to product jurisdiction

OCP jurisdiction-related activities included participating in the 

following:

• Enhancing the efficiency and transparency of the Pre-RFD 

Program

• Classification-related issues for e-cigarettes and other 

products that include tobacco

 

23 SMG 4103 is available at 

https://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/StaffManualGuides/UCM602810.pdf. 

24 83 FR 27609 (June 13, 2018), available at https://www.federalregister.gov/documents/2018/06/13/2018-

12634/alternative-or-streamlined-mechanisms-for-complying-with-the-current-good-manufacturing-practice. 

25 Available at https://www.govinfo.gov/content/pkg/FR-2018-12-12/pdf/2018-26840.pdf 26 Available at https://www.fda.gov/media/124138/download
25 FY 2018 OCP Performance Report

Additional Premarket Review Regulatory Initiatives

Type of Activity FY 2018 Accomplishments

Developing guidance and regulations

OCP chaired or led the following guidance-related activities:

• Continued to chair a cross-Center working group to finalize a 

guidance on human factors studies for combination products

• Continued to chair a cross-Center working group to begin 

development of a draft guidance for technical aspects of 

intravaginal ring drug-delivery combination products

• Chaired a cross-Center working group to develop a guidance 

for the technical considerations for demonstrating reliability 

of combination product emergency-use injectors

• Led the development of a Cures Act-mandated guidance on 

presubmissions for combination product and combination 

product agreement meetings

OCP participated in the development of: 

• Rule on De Novo classification 

• Draft guidance on the premarket principles and pathway 

availability for combination products

• Draft guidance on pre-submission facility inspection for 

generic drugs27

• Draft guidance on metered dose inhalers and dry powder 

inhalers28 

• Provision of combination product comments for citizen 

petition responses for specific types of generic combination 

products

• Draft guidance on comparative assessments, including 

human factors for generic drug-led and interchangeable 

biologic-led combination products29

• Final guidance on the selection of appropriate package type 

terms and recommendations for labeling injectable medical 

products packaged in multiple-dose, single-dose, and singlepatient use containers for human use

• Technical considerations for visual inspection for particulates 

in injectable solutions 

• Final guidance on regulatory considerations for human cells, 

tissues, and tissue-based products (including 

classification)30

• Comments on ISO standards development for certain 

syringes.

Assessing regulatory pathways for 

new products intended to be used 

with another sponsor’s alreadyapproved product

OCP continued to work with the Centers and OCC to assess 

approaches for resolving complex legal and public health issues 

associated with the marketing of products intended for use with 

other legally marketed products. This work also included 

preparations for a 21 CFR part 15 hearing.

 

27 Available at https://www.fda.gov/media/105794/download 28 Available at https://www.fda.gov/media/70851/download 29 Available at https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugsgen/documents/document/ucm621902.pdf

30 Available at https://www.fda.gov/media/124138/download
26 FY 2018 OCP Performance Report

Type of Activity FY 2018 Accomplishments

Participating in other inter-Center and 

Agency-wide working groups to 

clarify issues related to combined use 

of medical products

OCP led or participated in working groups with Centers and other 

Agency components regarding the following: 

• The appropriate regulatory pathway for novel technology 

diagnostics and biomarkers for use with drug or biological 

products

• Companion diagnostics

• The expansion of non-prescription drug availability

• The development of Agency thinking on the regulation of 

software as drug labeling 

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

Antimicrobial Resistance

Developing the 

consultative/collaborative review 

process and procedures

OCP, with the medical product Centers and other components of 

the Office of the Commissioner, completed an Inter-Center

consult process pilot intended to enable timely and consistent 

coordination and the efficient, consistent review of submissions, 

and launched the revised process. This activity included 

developing and presenting training materials, facilitating, 

monitoring, and assessing consult activities.

Additional Postmarket Review Regulatory Initiatives

Type of Activity FY 2018 Accomplishments

Participation in other InterCenter and Agency-wide 

working groups to clarify 

postmarket review issues 

related to combination 

products and guidance 

development

OCP participated in the following postmarket review activities:

• Continued to chair working groups relating to PMSR for combination 

products, focusing on the development of a draft guidance regarding 

the final rule and efforts to implement that rule, including the 

development of internal standard operating procedures 

• Continued to chair a working group and leadership body to support 

implementation of the final rule on CGMPs for combination products, 

including inspectional activities and expectations relating to premarket 

submissions

• Continued to work with Centers on track-and-trace regimes with 

respect to combination products, including Unique Device Identifier, 

numeric drug coding, and serialized numeric identifiers

• 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 
27 FY 2018 OCP Performance Report

Additional Activities and Accomplishments

Information Technology

OCP continued to coordinate and participate in cross-cutting information technology (IT) 

initiatives to enhance infrastructure and update guidances as appropriate to improve the 

efficiency, consistency, and reliability of information systems and communications within and 

among medical product Centers and between FDA and combination product sponsors and other 

interested stakeholders. OCP led efforts to improve staff access to IT systems needed for the 

review of combination products, to update PMSR Agency IT systems, and to develop new 

guidances on how stakeholders should engage with FDA in light of the final rule on PMSR for 

combination products.

External Outreach

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

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

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

Medical Instrumentation, Pharmaceutical Research and Manufacturers of America, and BIO) 

representing the drug, device, biological product, and combination product industries, as well as

by participating in industry conferences. Discussions and presentations focused on a wide 

range of topics, including emerging issues in combination product regulation, the role of OCP, 

policies and guidance documents under consideration, rulemakings, specific categories of 

combination products, particular regulatory issues, and stakeholder priorities for further action. 

Examples of FY 2018 outreach activities are included in the table below.

Type of Activity FY 2018 Accomplishments

Conducting presentations and 

outreach activities

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

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

educational outreach:

• Association for the Advancement of Medical Instrumentation/FDA 

International Conference on Medical Device Standards and Regulation, 

2018 

• 2018 Drug Information Association Annual Conference on Combination 

Products

• Parenteral Drug Association/FDA Joint Regulatory Conference 2018

• Drug Information Association Annual Meeting 2018

• Xavier University Health Combination Products Summit (September 

2018)

• 2018 Drug Information Association Complex Drug-Device Generic 

Combination Products Conference

• Medical Device Manufacturers Association 2018 FDA Forum
28 FY 2018 OCP Performance Report

(This page left blank intentionally.)
29 FY 2018 OCP Performance Report

Appendix

Appendix A: FY 2017 Updated Performance Detail

The table below reflects the 566 original applications received in FY 2017 initially classified into 

one of nine categories of combination products. 

Workload by Combination Product Category Number

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

Original NDAs 7 23 0 2 0 0 0 0 2 34

Original BLAs 0 0 8 0 0 1 0 0 0 9 

Original PMAs 0 0 0 5 1 0 2 0 2 10

Original 510(k)s 6 0 2 58 3 0 7 3 14 93

Original INDs 33 46 23 12 14 66 0 92 11 297

Original IDEs 6 0 0 27 0 0 4 3 7 47

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

ANDAs 27 40 0 0 0 0 0 0 1 68

Biosimilar BLAs 6 0 1 0 0 0 0 0 0 7 

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

Total 86 109 34 104 18 67 13 98 37 566 

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

Workload by Center Lead

The pie chart to the right shows the 

number and percentage of 

combination product applications 

received in FY 2017 by Center lead, 

as of September 30, 2018.

 

 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 

CBER 

53 

(9%)

CDER 

375

(67%)

CDRH

138 

(24%)

Combination Product 

Applications (n = 566)
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

10903 New Hampshire Avenue

Silver Spring, Maryland 20993-0002

Phone: 301-796-4850

This report is available on the FDA Home Page at: www.fda.gov and

the OCP Home Page at https://www.fda.gov/combination-products.