[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