[Federal Register Volume 61, Number 103 (Tuesday, May 28, 1996)]
[Notices]
[Pages 26523-26524]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-13386]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 95N-0200]


Guidance on Applications for Products Comprised of Living 
Autologous Cells Manipulated Ex Vivo and Intended for Structural Repair 
or Reconstruction; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance entitled ``Guidance on Applications for 
Products Comprised of Living Autologous Cells Manipulated Ex Vivo and 
Intended for Structural Repair or Reconstruction.'' The guidance was 
prepared by the Center for Biologics Evaluation and Research (CBER) in 
consultation with the Center for Devices and Radiological Health. The 
document is intended to provide guidance on FDA's approach to the 
regulation of living autologous cells manipulated ex vivo and intended 
for structural repair or reconstruction (Manipulated Autologous cells 
or MAS cells). The agency is also inviting comments on the guidance.

DATES: Written comments by August 26, 1996.

ADDRESSES: Submit written requests for single copies of the guidance 
entitled ``Guidance on Applications for Products Comprised of Living 
Autologous Cells Manipulated Ex Vivo and Intended for Structural Repair 
or Reconstruction'' to the Division of Congressional and Public Affairs 
(HFM-44), Center for Biologics Evaluation and Research, Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448. Send one 
self-addressed adhesive label to assist that office in processing your 
requests. The guidance may also be obtained by mail or FAX by calling 
the CBER Voice Information System at 1-800-835-4709.
    Persons with access to the INTERNET may obtain the document in 
several ways. Users of ``Web Browser'' software, such as Mosaic, 
Netscape, or Microsoft Internet Explorer may obtain this document via 
the World Wide Web by using the following Uniform Resource Locators:
    http://www.fda.gov/cber/cberftp.html
    ftp://ftp.fda.gov/CBER/
 The document may also be obtained via File Transfer Protocol (FTP). 
Requestors should connect to FDA's FTP Server, 
FTP.FDA.GOV(192.73.61.21). CBER documents are maintained in a 
subdirectory called ``CBER'' on the server. Logins with the user name 
of anonymous are permitted, and the user's e-mail address should be 
sent as the password. The ``READ.ME'' file in that subdirectory 
describes the available documents that may be available as an ASCII 
text file (*.TXT), or a WordPerfect 5.1 or 6.x document (*.w51,wp6), or 
both. Finally, the guidance can be obtained by ``bounce-back e-mail''. 
A message should be sent to: [email protected]''.
    Submit written comments on the guidance to the Dockets Managements 
Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 
1-23, Rockville, MD 20857. Two copies of any comments are to be 
submitted, except that individuals may submit one copy. Requests and 
comments should be identified with the docket number found in brackets 
in the heading of this document. A copy of the guidance and received 
comments are available for public examination in the Dockets Management 
Branch between 9 a.m. and 4 p.m., Monday through Friday.

FOR FURTHER INFORMATION CONTACT: Sharon A. Carayiannis, Center for 
Biologics Evaluation and Research (HFM-630), Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 301-594-
3074.

SUPPLEMENTARY INFORMATION:
    FDA had recently become aware of the clinical use of MAS cell 
products. MAS cells are defined as cells derived from a patient's 
tissues, which are manipulated ex vivo, and then implanted locally into 
the same patient with the intent of providing repair or reconstruction 
of a structure. The repair and reconstruction does not involve systemic 
action by the MAS cell product. Examples of MAS cells include 
chondrocytes expanded ex vivo and implanted in focal cartilage defects 
(see 60 FR 36808 at 36809 for additional information and references). 
The commercialization and distribution of expanded cartilage cells to 
provide a potential solution to a relatively common medical injury 
suggested that numerous patients could be receiving these cells within 
a short period of time.
    In light of the potential public health significance of the MAS 
cell products, the growth of a commercial industry potentially 
affecting a large number of patients, and the need to decide which 
existing regulatory authorities (e.g., device versus biologics) would 
be appropriate to apply or whether a new regulatory framework was 
required, the agency held a public hearing on November 16 and 17, 1995 
(60 FR 36808). The intent of the meeting was to solicit information on 
the nature and diversity of these products, and to receive comments on 
the formulation and implementation of any new regulatory requirements. 
The public hearing had 8 panels with 24 speakers, and there was general 
consensus that the establishment, the production process, and the MAS 
cell products should be of the highest quality. The speakers and 
attendees also agreed that MAS cell products should benefit the 
patient, but there was little consensus on the appropriate mechanism 
that should be used to show this benefit.
    In the Federal Register of March 7, 1996 (61 FR 9185), after 
reviewing the comments and further internal discussions, the agency 
published a notice announcing a Commissioner's roundtable to be held on 
March 15, 1996. The roundtable was held to present the elements of a 
planned regulatory framework intended to ensure patient safety and to 
demonstrate patient benefit, while accommodating the development of 
these therapies and the need for a flexible regulatory approach. Many 
of the concepts presented at the roundtable were derived from ongoing 
FDA Reinventing Government (REGO) initiatives. In the same Federal 
Register notice, FDA also invited the submission of written comments 
concerning FDA's draft plan for the regulation of MAS cells. Based on 
the discussions at the March 15, 1996, roundtable and on a review of 
all comments received, FDA has decided that, in light of the existing 
and increased flexibility provided by REGO initiatives, FDA will apply 
the regulatory framework as detailed and explained in the guidance. 
CBER is

[[Page 26524]]

designated as the agency component with primary jurisdiction for the 
premarket review and regulation of MAS cell products. The products are 
subject to licensure as biological products under section 351 of the 
Public Health Service Act (42 U.S.C. 262).
    The guidance document includes discussions on the following: (1) 
Background and recent events; (2) regulatory plan, including: A summary 
and discussions of products to be regulated, registration and 
inspection of establishments, clinical studies, investigational phase 
and requirements for premarket approval, cost recovery, marketing 
application, chemistry, manufacturing and controls section of a 
biologics license application, formulation of an intercenter working 
group, contracting of manufacture, lot release, and current good 
manufacturing practice requirements; (3) registration and application 
submission; and (4) submission of comments.
    As with other procedural guidance documents, FDA does not intend 
this guidance to be all-inclusive. Alternative approaches could be 
warranted in specific situations, and certain aspects might not be 
applicable in all situations. If an applicant believed a procedure 
described in this guidance was inapplicable to a specific situation for 
a particular product, the applicant could provide, for CBER's 
consideration, information supporting an alternative process. If an 
applicant chooses to use an alternative process, the applicant may wish 
to discuss the matter further with the agency to prevent expenditure of 
money and resources on activities that later might be determined to be 
inappropriate to FDA. Although this guidance does not create or confer 
any rights for or on any person, and does not operate to bind FDA or 
the public, it does represent the agency's current thinking on the 
regulation of MAS cell products.
    Interested persons may, on or before (insert date 90 days after 
date of publication in the Federal Register), submit written comments 
on the guidance to the Dockets Management Branch (address above). Two 
copies of any comments are to be submitted, except that individuals may 
submit one copy. Comments and information are to be identified with the 
docket number found in brackets in the heading of this document. The 
guidance and received comments may be seen in the office above between 
9 a.m. and 4 p.m., Monday through Friday.
    Received comments on this document will be considered in 
determining whether revisions to the guidance are warranted.

    Dated: May 22, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-13386 Filed 5-23-96; 11:13 am]
BILLING CODE 4160-01-F