[Federal Register Volume 61, Number 82 (Friday, April 26, 1996)]
[Notices]
[Pages 18612-18613]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-10426]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
[Docket No. 96D-0132]
Guidance Concerning Demonstration of Comparability of Human
Biological 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 document entitled ``FDA Guidance Concerning
Demonstration of Comparability of Human Biological Products, Including
Therapeutic Biotechnology-derived Products.'' Manufacturing process,
equipment, and/or facilities changes have the potential to alter a
product and affect its safety, identity, purity, and potency.
Therefore, manufacturers should carefully assess such changes and
should evaluate the product resulting from these changes for
comparability to the pre-existing product. This guidance document is
intended to address the concept of comparability and delineates those
analyses that manufacturers should perform and which FDA will evaluate
to allow more rapid implementation of manufacturing changes for these
types of products.
DATES: Written comments may be submitted at any time, however, to
ensure comments are considered for the next revision, they should be
submitted by July 25, 1996.
ADDRESSES: CBER Information: Submit written requests for single copies
of the document entitled ``FDA Guidance Concerning Demonstration of
Comparability of Human Biological Products, Including Therapeutic
Biotechnology-derived Products'' to the Division of Congressional and
Public Affairs (HFM-44), Center for Biologics Evaluation and Research
(CBER), 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 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 (URL's):http://
www.fda.gov/cber/cberftp.htmlftp://ftp.fda.gov/CBER/
The document may also be obtained via File Transfer Protocol (FTP).
Requesters should connect to the FDA FTP Server, FTP.FDA.GOV
(192.73.61.21). The Center for Biologics Evaluation and Research (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 WordPerfect 5.1 or 6.x
document (*.w51,wp6), or both. Finally, the document can be obtained by
``bounce-back e-mail''. A message should be sent to:
comptest@a1.cber.fda.gov''.
CDER Information: For additional copies of this guidance, contact the
Division of Communications Management (HFD-210), Center for Drug
Evaluation and Research (CDER), Food and Drug Administration, 5600
Fisher's Lane, Rockville, MD 20857, 301-594-1012. Send one self-
addressed adhesive label to assist that office in processing your
requests. An electronic version of this guidance is also available via
Internet using FTP, Gopher or the World Wide Web (WWW). For FTP,
connect to the CDER anonymous FTP server at cdvs2.cder.fda.gov and
change to the ``guidance'' directory. For Gopher, connect to the CDER
Gopher server at gopher.cder.fda.gov and select the ``Industry
Guidance'' menu option. For WWW, connect to the FDA Home Page at http:/
/www.fda.gov./fdahomepage.htlm.
Submit written comments on the document to the Dockets Managements
Branch (HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm.
1-23, Rockville, MD 20857. Corporations should submit two copies of any
comments and 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 document and received comments
are available for public examination in the
[[Page 18613]]
Dockets Management Branch between 9 a.m. and 4 p.m., Monday through
Friday.
FOR FURTHER INFORMATION CONTACT: Annette Ragosta, 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 acknowledges that changes in product
manufacture may occur during product development and subsequent to
product approval. Manufacturers frequently upgrade and refine a
product's production process as technology advances and as they gain
experience with the product. Historically, because of the limited
ability to characterize the identity and structure of the clinically
active component(s) and measure its activity, a biological product was
often defined by its manufacturing process, and manufacturers of
biological products sought to minimize changes to the manufacturing
process to avoid performing additional clinical studies to verify the
safety, purity, and potency of the finished product. Due to advances in
biologics research and manufacturing, including the ability to make
well-characterized biotechnology-derived products, a manufacturer may
change a manufacturing process without FDA requiring additional
clinical studies if test data demonstrate that the product is
comparable to the product manufactured before the change. Therefore,
FDA is publishing this guidance document to further clarify situations
in which sponsors may make manufacturing changes and perform
comparability testing to assure that the approved product is pure,
potent, and safe.
Manufacturers should perform comparability testing to demonstrate
that identity, purity, potency, and safety of the product have not been
affected by changes in the manufacturing process, equipment, or
facilities. This guidance document discusses principles and categories
of tests which may be performed to demonstrate product comparability,
but does not discuss specific manufacturing changes. Comparability
testing programs may include a combination of analytical testing,
bioassays, preclinical animal studies, and clinical studies. Since each
product may present unique concerns, the type of change, the relevance
of validated analytical and biological assays used, the stage of
product development, and the clinical program should be considered by
manufacturers when designing a comparability program. FDA will take all
of these into consideration when reviewing the comparability data that
are submitted. Sponsors are encouraged to discuss proposed testing
programs with FDA before implementing them, especially in those cases
where they expect differences to result from the manufacturing changes.
This document does not describe how changes are to be reported or which
changes require prior approval. Manufacturers should consult current
regulations and guidance documents regarding reporting and approval
submissions.
As with other guidance documents, FDA does not intend this document
to be all inclusive. The document is intended to provide information
and does not set forth requirements. Manufacturers may follow the
document or may choose to use alternative procedures that are not
provided in this document. If a manufacturer chooses to use alternative
procedures, that manufacturer may wish to discuss the matter further
with FDA to prevent expenditure of resources to generate data on
activities that FDA may later determine to be unacceptable.
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
demonstration of comparability of human biological products, including
therapeutic biotechnology-derived products.
Interested persons may submit to the Dockets Management Branch
(address above) written comments on the guidance document. FDA will
review the comments received and if appropriate consider preparing a
revised guidance document based upon that review. However, CBER notes
that it has made comparability assessments when approving /products in
the past and will continue to do so during the comment period. FDA will
announce the availability of this revised guidance document in the
Federal Register if FDA revises its comparability policy as a result of
public comment.
Dated: April 22, 1996
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-10426 Filed 4-25-96; 8:45 am]
BILLING CODE 4160-01-F
