[Federal Register Volume 67, Number 94 (Wednesday, May 15, 2002)]
[Notices]
[Pages 34722-34724]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-12171]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 02N-0169]


Combination Products Containing Live Cellular Components; Public 
Hearing

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public hearing; request for comments.

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SUMMARY: The Food and Drug Administration (FDA) is announcing a public 
hearing to discuss the jurisdictional classification, assignment, and 
premarket review of certain products that consist of living human cells 
in combination with a device matrix. The hearing will focus on products 
that are intended for wound healing (e.g., wound repair or skin 
regeneration, replacement, or reconstruction), although the information 
obtained may also be pertinent to questions concerning other 
combination products containing live cells. Combination products that 
include human cell or tissue components have significant potential to 
enhance the public health. The purpose of the hearing is to solicit 
information and views from interested persons, including scientists, 
clinical investigators, professional groups, trade groups, commercial 
enterprises, and consumers, on the issues and concerns relating to the 
premarket review and regulation of these combination products. To 
assist in the development of a consistent policy on jurisdiction for 
these products, FDA is interested in responses to specific questions 
and any other pertinent information stakeholders would like to share.

DATES: The public hearing will be held on Monday, June 24, 2002, from 9 
a.m. to 5 p.m. Submit written or electronic notices of participation by 
June 14, 2002. Written comments will be accepted until August 23, 2002.

ADDRESSES: The public hearing will be held at the Double Tree Hotel, 
Plaza II and III, 1750 Rockville Pike, Rockville, MD 20852. Directions 
to the hotel can be found at www.doubletreerockville.com. Submit 
written notices of participation and comments to the Dockets Management 
Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 
1061, Rockville, MD 20852, e-mail: [email protected]. Submit 
electronic comments to http://www.accessdata.fda.gov/scripts/oc/dockets/meetings/meetingdocket.cfm. Transcripts of the hearing will be 
available for review at the Dockets Management Branch and on the 
Internet at http://www.fda.gov/ohrms/dockets.

FOR FURTHER INFORMATION CONTACT: Karen Wesley, Office of the Ombudsman, 
Office of Communications and Constituent Relations (HF-7), Food and 
Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-
3390, FAX 301-480-8039, e-mail: [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing a public hearing to discuss the jurisdictional 
classification, assignment, and premarket review of products that 
consist of living human cells in combination with a device matrix that 
are intended for wound healing. The meeting is another step in the 
agency's continuing effort to clarify and refine its regulatory 
approach to products that are comprised in whole or in part of living 
cells or tissues.
    As the field of cell and tissue therapy has evolved, the agency has 
developed policies and practices to regulate these emerging products 
appropriately. For example, FDA is developing a risk-based regulatory 
approach for human cells, tissues, and cellular and tissue-based 
products (HCT/Ps). Under this approach, certain HCT/Ps would be subject 
to various requirements, including registration and listing, donor 
eligibility requirements, and good tissue practice requirements, but 
would not be subject to premarket review and approval. Other HCT/Ps, 
including combination products consisting of a cellular product 
combined with a device, would be subject to premarket review and 
approval.
    Most cell therapies currently under development involve the use of 
cells alone, or in combination with biological products, such as 
cytokines or growth factors. However, in recent years sponsors have 
begun to combine human cells with other FDA-regulated articles, 
including devices or drug products. The combination of two distinct 
components that would normally be regulated under different regulatory 
authorities introduces additional factors to consider in the 
determination of primary jurisdiction and the application of 
appropriate regulatory authorities. In accordance with section 
503(g)(1) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 
353(g)(1), the agency is required to assign primary jurisdiction for 
premarket review of combination products based on the product's 
``primary mode of action.'' In order to determine a combination 
product's primary mode of action the agency must be able to identify 
how the product acts on the body and to determine the relative 
contribution of each of its component parts.
    In the absence of clear scientific data demonstrating which mode of 
action is primary, other factors have been considered to determine 
assignment of review responsibility within FDA. Historically, these 
other factors have included the guidance provided by the intercenter 
agreements, determination of the most novel element or component with 
the greatest safety risk and indication for use. Many of these products 
have been characterized as ``cultured skin'' products or interactive 
wound dressings and have been reviewed and regulated by the Center for 
Devices and Radiological Health (CDRH) under medical device 
authorities. Several such products have gone through CDRH administered 
review and are now marketed under approved premarket approval 
applications. FDA is soliciting information to determine whether this 
class of products should be transferred to the Center for Biologics 
Evaluation and Research (CBER) for premarket review and regulation.

II. Purpose and Scope of the Hearing

    The promise of combination products that use living cells in 
combination with a device matrix for wound healing may be significant. 
Because such products combine cell and non-cell components successful 
development and marketing of these products may be slowed by 
uncertainty about jurisdiction, particularly as it relates to the 
nature and scope of regulatory requirements that must be met in order 
to bring these products to market. Moreover, such products have 
increasingly been the subject of questions regarding both jurisdiction 
and pre and postmarket requirements. The agency recognizes that it may 
need to modify existing paradigms to address the unique characteristics 
of these combinations.
    In light of the regulatory and scientific issues posed by such 
combination products, the agency is holding a public hearing to 
solicit: (1) Information about these products, (2) recommendations on 
the formulation and implementation of a consistent policy for product 
assignment, and (3) appropriate requirements for approval.
    The hearing will focus on a discussion of combination products that 
consist of autologous or allogeneic living human cells combined with a 
device matrix for wound healing. The agency notes that some of the 
products

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that consist of living cells combined with a device matrix intended for 
wound healing are now assigned to CDRH. Depending upon the information 
presented at the hearing, the agency could conclude that the primary 
mode of action of some or all of these products is that of the cell 
component, and that the product(s) should therefore be reassigned to 
CBER.
    Single entity products, combination products containing bone, 
ligament and vascular products used for structural purposes, and drug-
device combination products are beyond the scope of this hearing. In 
addition, the hearing will not consider products intended for purposes 
other than wound healing, such as encapsulated pancreatic cells 
intended for implantation to produce insulin to treat diabetes.
    Combination products that contain a gene therapy component are also 
beyond the scope of this hearing. The term gene therapy includes all 
products that contain genetic material administered to modify or 
manipulate the expression of genetic material or to alter the 
biological properties of living cells.

III. Issues for Discussion

    The agency recognizes the importance of promoting the public health 
by promptly and efficiently reviewing clinical research and taking 
appropriate action on the marketing of regulated products in a timely 
manner, and of protecting the public health by assuring the safety and 
effectiveness of regulated medical products. New technologies and 
products that result from the combination of two distinct components 
provide not only unique scientific questions, but also challenges 
related to where and how the products should be regulated in order to 
ensure adequate, predictable, and consistent regulatory oversight. This 
public hearing is being held to discuss the classification, assignment, 
and premarket review of combination products comprised of live human 
cells used in combination with a device matrix for wound healing (e.g., 
wound repair, or skin regeneration, replacement or reconstruction). To 
assist in the development of a consistent policy on jurisdiction for 
these products, the agency invites information and comments on the 
following:
    1. What are the public health concerns related to these combination 
products as a whole and with respect to their individual components? 
What information should the agency require in the premarket submission 
to demonstrate the safety and efficacy of combination products that 
contain live cells used in combination with a device matrix for wound 
healing (e.g., wound repair, or skin regeneration, replacement or 
reconstruction)? What regulatory requirements are necessary to ensure 
that adequate manufacturing controls are in place for both the device 
and live cell components? What other issues are important (e.g., 
clinical trial design, informed consent, infectious disease concerns)?
    2. Given that primary mode of action determines jurisdiction for 
combination products, what information should the agency consider in 
identifying the level of contribution of each component to the 
therapeutic effect of the product? For example, skin replacement 
products are intended to act as wound coverings (historically 
considered a device action), and as mediators of tissue regeneration or 
repair by providing a living substrate to grow replacement tissue and 
through the production of soluble factors (historically considered to 
be biological product activities). What information should the agency 
consider in determining which action is primary?
    3. In instances where both components of a combination product 
containing live cells appear to make a significant contribution to the 
therapeutic effect of the product and it is not possible to determine 
which mode of action is primary, what other factors should the agency 
consider in the assignment of primary jurisdiction? Is there a clear 
hierarchy among these additional factors that should be observed in 
order to ensure an adequate review? Should these same factors be used 
to determine the appropriate type of premarket application?

IV. Notice of Hearing Under 21 CFR Part 15

    The Commissioner of Food and Drugs (the Commissioner) is announcing 
that the public hearing will be held in accordance with part 15 (21 CFR 
part 15). The presiding officer will be the Commissioner's designee, 
the Senior Associate Commissioner for Communications and Constituent 
Relations. The presiding officer will be accompanied by senior 
management from CBER, CDRH, and the Center for Drug Evaluation and 
Research (CDER).
    Persons who wish to participate in the part 15 hearing must file a 
written or electronic notice of participation with the Dockets 
Management Branch (see ADDRESSES) before June 14, 2002. To ensure 
timely handling, any outer envelope should be clearly marked with the 
docket number listed at the head of this notice along with the 
statement ``Combination Products Containing Live Cellular Components 
Hearing.'' Groups should submit two written copies. The notice of 
participation should contain the person's name; address; telephone 
number; affiliation, if any; the sponsor of the presentation (e.g., the 
organization paying travel expenses or fees), if any; a brief summary 
of the presentation; and approximate amount of time requested for the 
presentation. The agency requests that interested persons and groups 
having similar interests consolidate their comments and present them 
through a single representative. After reviewing the notices of 
participation and accompanying information, FDA will schedule each 
appearance and notify each participant by telephone of the time 
allotted to the person and the approximate time the person's oral 
presentation is scheduled to begin. If time permits, FDA may allow 
interested persons attending the hearing who did not submit a written 
or electronic notice of participation in advance to make an oral 
presentation at the conclusion of the hearing. The hearing schedule 
will be available at the hearing. After the hearing, the hearing 
schedule will be placed on file in the Dockets Management Branch under 
the docket number listed at the head of this document.
    Under Sec.  15.30(f), the hearing is informal, and the rules of 
evidence do not apply. No participant may interrupt the presentation of 
another participant. Only the presiding officer and panel members may 
question any person during or at the conclusion of each presentation.
    Public hearings under part 15 are subject to FDA's policy and 
procedures for electronic media coverage of FDA's public administrative 
proceedings (part 10, subpart C (21 CFR part 10, subpart C)). Under 
Sec.  10.205, representatives of the electronic media may be permitted, 
subject to certain limitations, to videotape, film, or otherwise record 
FDA's public administrative proceedings, including presentations by 
participants. The hearing will be transcribed as stipulated in 
Sec. 15.30(b). The transcript of the hearing will be available on the 
Internet at http://www.fda.gov/ohrms/dockets, and orders for copies of 
the transcript can be placed at the meeting or through the Dockets 
Management Branch (see ADDRESSES).
    Any handicapped persons requiring special accommodations to attend 
the hearing should direct those needs to the contact person (see FOR 
FURTHER INFORMATION CONTACT).
    To the extent that the conditions for the hearing, as described in 
this document, conflict with any provisions set out in part 15, this 
notice acts as a

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waiver of those provisions as specified in Sec. 15.30(h).

V. Request for Comments

    Interested persons may submit to the Dockets Management Branch (see 
ADDRESSES) written or electronic notices of participation and comments 
for consideration at the hearing by June 14, 2002. To permit time for 
all interested persons to submit data, information, or views on this 
subject, the administrative record of the hearing will remain open 
following the hearing until August 23, 2002. Persons who wish to 
provide additional materials for consideration should file these 
materials with the Dockets Management Branch (see ADDRESSES) by August 
23, 2002. Two copies of any written comments are to be submitted, 
except that individuals may submit one copy. Comments are to be 
identified with the docket number found in brackets in the heading of 
this document. Received comments may be seen in the Dockets Management 
Branch between 9 a.m. and 4 p.m., Monday through Friday.

VI. Electronic Access

    Persons with access to the Internet may obtain more information 
about this hearing or combination products in general at http://www.fda.gov.

    Dated: April 29, 2002.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 02-12171 Filed 5-10-02; 4:33 pm]
BILLING CODE 4160-01-S