SMG 4103 (03/27/2018) 1

SMG 4103

FDA STAFF MANUAL GUIDES, VOLUME IV - AGENCY PROGRAM 

DIRECTIVES

COMBINATION PRODUCTS

EXPECTATIONS AND PROCEDURES FOR ENGAGEMENT AMONG 

MEDICAL PRODUCT CENTERS AND OFFICE OF COMBINATION 

PRODUCTS ON REGULATIONS AND GUIDANCE PERTAINING TO 

COMBINATION PRODUCTS

Effective Date: March 27, 2018

1. Purpose

2. Definitions

3. Policy

4. Background

5. Responsibilities

6. Procedures

7. Effective Date

8. History

1. PURPOSE.

The purpose of this staff manual guide is to ensure the necessary subject 

matter experts and policy staff from the medical product Centers (Center for 

Biologics Evaluation and Research (CBER), Center for Drug Evaluation and 

Research (CDER), Center for Devices and Radiological Health (CDRH)), and 

the Office of Combination Products (OCP) are engaged in a timely manner as 

needed for development and clearance of regulations and guidance 

documents that pertain to combination products1 and that this engagement is 

transparent to stakeholders.2

2. DEFINITIONS.

Component: CDER, CBER, CDRH or OCP

Lead Component: The Component that has the lead for developing the 

guidance or regulation

 1 See 21 CFR 3.2(e).

2 Engagement of other FDA components (including other Centers, Office of Medical Products and 

Tobacco, Office of Chief Counsel and Office of Regulatory Affairs) may also be appropriate; 

however, when to engage such components is beyond the scope of this guide.
SMG 4103 (03/27/2018) 2

Consulting Component(s): Component(s) that assist(s) the Lead 

Component in developing the guidance or regulation

3. POLICY.

It is FDA policy that guidance and regulation efforts led by one of the three 

medical product Centers or OCP (“Lead Component”) will include staff 

members from the other Component(s) (“Consulting Component(s)”), as 

appropriate, when the guidance or regulation pertains to combination 

products.3 The engagement of any such Consulting Component(s) should be 

timely and the level of participation should be appropriate to ensure 

identification of concerns. The Federal Register notices announcing 

regulations and guidance and the guidances themselves should clearly 

indicate the Components involved in the development of the policy.

4. BACKGROUND.

Policy pertaining to combination products is a growing area that requires 

guidance and regulation development for FDA. Combination product 

guidance and/or regulation often require expertise from different medical 

product Centers and OCP to ensure that cross-cutting regulatory matters are 

addressed in a comprehensive and consistent manner and that cross-cutting 

processes and practices are considered. Recent legislative efforts, including 

passage of the 21st Century Cures Act and user fee authorizations, reinforce 

the need for collaboration among FDA Components on policy pertaining to 

combination products. Although OCP is responsible for ensuring the timely, 

effective and aligned premarket review of combination products and their 

consistent and appropriate postmarket regulation, either OCP or an individual 

Center may initiate the development of a guidance or regulation pertaining to 

combination products.

5. RESPONSIBILITIES.

Lead Component:

1. Notifies potential Consulting Component(s) of a proposal to revise an 

existing guidance or regulation or to develop a new guidance or 

regulation pertaining to combination products.

2. Engages with the Consulting Component(s) in a manner consistent 

with the level of participation agreed upon with the Consulting 

Component. As needed:

 3 This procedure is aligned with, but does not replace, FDA-wide and Center procedures such as 

the Quality System for Regulations (see SMG 1118.6) or other Agency guidance templates.
SMG 4103 (03/27/2018) 3

a. Provides timely access to documents and materials for review by 

Consulting Component(s).

b. Establishes timelines for completion of deliverables related to the 

regulation or guidance. Timelines should take into account, 

whenever possible, the resource availability/capacity of the 

Consulting Component(s).

Consulting Component(s):

1. Reviews the consulting request from the Lead Component and 

determines whether the Consulting Component(s) need to participate 

in this activity.

2. Identifies and approves the staff members, if any, to support the 

regulation or guidance effort of the Lead Component.

3. Participates actively in Lead Component regulation or guidance 

workgroups, when such level of participation has been agreed upon 

between Components.

4. Provides timely review of documents as requested by the Lead 

Component and consistent with the level of participation agreed upon 

with the Lead Component.

6. PROCEDURES.

A. When should the Lead Component contact another Component to 

determine whether there is a need to engage that Component in a 

regulation or guidance development effort?

1. The need for engagement and the level of participation with other 

Components should be considered at the initiation phase for a 

regulation or guidance that pertains to a combination product. The 

Lead Component should contact all Components that will be or may be 

impacted by the regulation or guidance effort. See Section C below for 

additional discussion of “level of participation.”

B. What is the process for contacting and coordinating with potential 

Consulting Components?

1. The Lead Component should notify each potential Consulting 

Component of the need to engage in a regulation or guidance effort 

pertaining to a combination product. The contact list below should be 
SMG 4103 (03/27/2018) 4

used for the initial communication, which should include the desired 

level of participation, expertise needed, and anticipated timeframe.

Contact List:

CBER: CBERDocDist@fda.hhs.gov

CDER: CDER-ORPRequests@fda.hhs.gov with cc to

CDERProductJurisdiction@fda.hhs.gov

CDRH: CDRHOCDClearanceTracker@fda.hhs.gov with cc to

CDRHProductJurisdiction@fda.hhs.gov

OCP: combination@fda.gov

2. The Lead Component and potential Consulting Component(s) should 

agree on what, if any, expertise is needed from the Consulting 

Component.

3. The deadline for completing the regulation or guidance effort should be 

set by the Lead Component. Where possible, the Consulting 

Component(s) should be given a minimum of 30 days to review unless 

a shorter timeframe is justified. If the Lead Component deadline does 

not provide sufficient time to complete the review, the Consulting 

Component and Lead Component should agree on an alternative 

timeframe. (see below).

4. The Lead Component should discuss the timeframes with the 

Consulting Component and take into account the Consulting 

Component’s resource availability/capacity of the Consulting 

Component(s) when establishing timeframes for the guidance or 

regulation effort, to the extent this is feasible in light of the 

circumstances (e.g., whether the action is needed to address a public 

health emergency or other priorities beyond the control of the Lead 

Component, such as compliance with statutorily imposed deadlines).

C. What participation by Consulting Components and public 

documentation of their participation are appropriate?

1. The Lead Component and Consulting Component(s) should determine 

early in the development process the level of participation appropriate 

to enable Consulting Component(s) to provide timely, informed input 

on issues related to their expertise and responsibilities.

Examples of a Consulting Component’s engagement include:
SMG 4103 (03/27/2018) 5

• Determining that participation in the effort is not necessary

• Participating regularly in a workgroup

• Drafting specific content for the guidance or regulation

• Consulting on and/or reviewing guidance or regulation content 

generated by the Lead Component

• Clearing the regulation or guidance

With the agreement of the Lead Component and Consulting 

Component(s), a Consulting Component can be included in the 

clearance process without having to participate otherwise in 

development of the regulation or guidance, if such limited engagement 

will enable the Consulting Component to engage effectively and in a 

timely manner.

2. The staff participating for a Consulting Component should be approved 

at the level of an Office director or higher, or designee(s). The staff 

participating from a Consulting Component are the Consulting 

Component’s representatives and, as such: (i) are expected to present 

the views of the Component on policy matters relevant to that 

Consulting Component, and (ii) are responsible for obtaining timely 

input from appropriate policy leads in their Component while 

participating in development of the guidance or regulation.

3. Depending on the level of participation by the Consulting 

Component(s), extent of reliance on that Component’s expertise, 

and/or the significance of the impact the regulation or guidance has on 

the Consulting Component(s), the name of the Consulting 

Component(s) should be:

• Listed on the cover page for a guidance, and/or

• Listed in the body of the Federal Register notice for a guidance or 

regulation, and/or

• Identified in a footnote in the guidance or regulation (stating, for 

example, “This [guidance][regulation] has been prepared by the 

[Lead Component] in consultation with [name of the Consulting 

Component(s)].”)
SMG 4103 (03/27/2018) 6

4. Unless the Lead and Consulting Component(s) have agreed that no 

participation is needed,4 the Lead Component will obtain formal 

clearance from the Consulting Component(s) in the Federal Register 

Document Tracking System (FRDTS), or its successor system.

7. EFFECTIVE DATE.

The effective date of this guide is March 27, 2018.

8. Document History - SMG 4103, Expectations and Procedures for 

Engagement Among Medical Product Centers and Office of 

Combination Products on Regulations and Guidance Pertaining to 

Combination Products

STATUS 

(I, R, C)

DATE 

APPROVED

LOCATION 

OF CHANGE 

HISTORY

CONTACT APPROVING OFFICIALS

Initial 03/26/2018 N/a Office of Combination 

Products (OCP)

Rachel Sherman, FDA Principal 

Deputy Commissioner

Back to Agency Program Directives, Volume IV (4000 - 9100)

 4 Such agreement may be case-by-case or categorical, approved at the Office director or 

equivalent level.