[Federal Register Volume 62, Number 7 (Friday, January 10, 1997)]
[Notices]
[Pages 1460-1461]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-579]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 95N-0200]
Guidance for the Submission of Chemistry, Manufacturing, and
Controls Information and Establishment Description for Autologous
Somatic Cell Therapy Products; 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 for the Submission of
Chemistry, Manufacturing, and Controls Information and Establishment
Description for Autologous Somatic Cell Therapy Products.'' This
guidance, prepared by the Center for Biologics Evaluation and Research
(CBER) in consultation with the Center for Devices and Radiological
Health, is intended to assist applicants in the preparation of the
chemistry, manufacturing, and controls (CMC) section and the
establishment description section of a biologics license application
(BLA) or in the preparation of a product license application (PLA) and
establishment license application (ELA) for all autologous somatic cell
therapy products. This guidance may assist in complying with certain
requirements in the Code of Federal Regulations.
DATES: Written comments may be submitted at any time; however, comments
submitted by April 10, 1997, will be considered for the next revision.
ADDRESSES: Submit written requests for single copies of the guidance
entitled, ``Guidance for the Submission of Chemistry, Manufacturing,
and Controls Information and Establishment Description for Autologous
Somatic Cell Therapy Products'' to the Office of Communication,
Training and Manufacturers Assistance (HFM-40), 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 document may
also be obtained by mail or by calling the CBER Voice Information
System at 1-800-835-4709, or 301-827-1800, or FAX at 1-800-CBER-FAX, or
301-827-3844.
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).
Requests should connect to the 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 which may be available as an ASCII
text file (*.TXT), or a Word Perfect 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:
Over the last several years, FDA has worked to clarify its approach
to the
[[Page 1461]]
regulation of products that are comprised in whole or in part of living
cellular materials. Recognizing that sponsors developing tissue and
cell based therapies would soon want to make these products
commercially available, FDA issued a notice in the Federal Register of
October 14, 1993 (58 FR 53248), entitled ``Application of Current
Statutory Authorities to Human Somatic Cell Therapy Products and Gene
Cell Therapy Products;'' this notice explained the regulatory framework
for somatic cell and gene therapy products, but it did not provide
detailed technical guidance. As announced in the Federal Register of
July 18, 1995 (60 FR 36808), FDA held a public hearing on November 16
and 17, 1995, to solicit information on the nature and diversity of a
subset of autologous somatic cell therapy products for structural
repair or reconstruction called manipulated autologous structural cell
products (MAS cell products) and to receive comments on the formulation
and implementation of any new regulatory requirements. As announced in
the Federal Register of March 7, 1996 (61 FR 9185), the agency held a
Commissioner's roundtable public meeting on March 15, 1996, to present
the elements of a planned regulatory framework intended to help ensure
patient safety and confirmation of patient benefit, while accommodating
the development of these therapies and the need for a flexible
regulatory approach. Many of the concepts presented at the meetings
were derived from ongoing FDA Reinventing Government initiatives. In
the Federal Register of May 28, 1996 (61 FR 26523), FDA announced the
availability of a guidance document entitled ``Guidance on Applications
for Products Comprised of Living Autologous Cells Manipulated Ex Vivo
and Intended for Structural Repair or Reconstruction.'' FDA now is
providing the CMC guidance document that describes product
characterization and establishment information for MAS cell products
and other autologous somatic cell therapy products. This document is
intended to assist manufacturers of all autologous somatic cell therapy
products, whether used for structural repair or reconstruction, or for
other purposes.
As outlined in the President's November 1995, National Performance
Review, ``Reinventing the Regulation of Drugs Made From
Biotechnology,'' and as part of FDA's continuing effort to reduce
unnecessary burdens for industry without diminishing public health
protection, FDA committed to using a standardized, single application
format for drug and biological product approvals. An interim form for
submission of the BLA, FDA Form 3439, is available from the Office of
Communication, Training and Manufacturers Assistance (address above).
Use of this form is voluntary. Establishments wishing to engage in
clinical studies of autologous somatic cell therapy products, including
MAS cell products, should submit an investigational new drug
application (IND). Establishments seeking approval of autologous
somatic cell therapy products for clinical use should either submit, as
appropriate, a BLA or a product license application (PLA) and companion
establishment license application (ELA).
The information FDA received at the public hearing of November 16
and 17, 1995, as well as comments received on the FDA Commissioner's
roundtable meeting of March 15, 1996, were considered in developing the
guidance for preparation of the CMC and establishment description
sections of the BLA for autologous somatic cell therapy products.
The guidance document is divided into three parts. The general
information section provides background information. Part 1, the CMC
section, is divided into the following sections: (1) Introduction; (2)
Biological Substance/Product, including discussions of Description and
Characterization, Manufacturer(s), and Method(s) of Manufacture,
Process Controls, Specifications/Analytical Methods, Container and
Closure Systems/Shipping Containers, and Biological Substance
Stability; (3) Biological Product, including discussions of Method(s)
of Manufacture and Packaging, Specifications and Test Methods for Final
Biological Product, Biological Product Stability, Container and Closure
System, and Microbiology; (4) Environmental Assessment; and (5) Method
Validation. Part 2, the establishment description section, provides a
description of establishment information that should be submitted and
related good manufacturing practice (GMP) controls for the manufacture
of autologous somatic cell therapy products. Part 2 is divided into the
following sections: (1) Introduction; (2) General Information; (3)
Water Systems, including discussions of General Description of Water
System, Validation Summary and Routine Monitoring; (4) Heating,
Ventilation and Air Conditioning Systems; and (5) Contamination/Cross
Contamination Issues, including discussions of Cleaning Procedures and
Validation and Containment Features. This document provides guidance to
manufacturers for providing the information describing establishment
standards and GMP controls that would be submitted as part of the BLA
or PLA and ELA.
As with other procedural guidance documents, FDA does not intend
that this guidance would 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 alternative processes, 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 by FDA. Additionally, FDA intends to further revise this
guidance, as needed. FDA also encourages applicants who use the BLA to
contact CBER to discuss use of the application further inasmuch as the
agency's experience with its use will evolve. Although this guidance
document 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 CMC and establishment description
sections of a BLA or PLA and ELA submitted for an autologous somatic
cell therapy product.
Interested persons may, on or before April 10, 1997, submit written
comments on the guidance document 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.
Written comments on this document will be considered in determining
whether revisions to the guidance are warranted.
Dated: January 6, 1997.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 97-579 Filed 1-9-97; 8:45 am]
BILLING CODE 4160-01-F