[Federal Register: May 15, 2002 (Volume 67, Number 94)]
[Notices]
[Page 34722-34724]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr15my02-91]
[[Page 34722]]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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: FDADockets@oc.fda.gov. 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: ombuds@oc.fda.gov.
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
[[Page 34723]]
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
[[Page 34724]]
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