[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: 
``[email protected]''.
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