[Federal Register Volume 59, Number 148 (Wednesday, August 3, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-18846]
[[Page Unknown]]
[Federal Register: August 3, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 94D-0259]
Draft ``Points To Consider in the Manufacture and Testing Of
Monoclonal Antibody Products For Human Use;'' 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 draft points to consider (PTC) document entitled
``Points to Consider in the Manufacture and Testing of Monoclonal
Antibody Products For Human Use.'' The draft PTC document is intended
to assist sponsors and investigators of monoclonal antibody (mAb)
products intended for human use. This document revises a 1987 document
entitled ``Points to Consider (PTC) in the Manufacture and Testing of
Monoclonal Antibody Products for Human Use.'' The updated version
contains the general guidance from the Center for Biologics Evaluation
and Research (CBER) regarding monoclonal antibody product development,
including information to be submitted when filing an investigational
new drug application (IND) and product license application (PLA).
DATES: Comments by October 3, 1994.
ADDRESSES: Submit written requests for single copies of the draft PTC
document to the Congressional and Consumer Affairs Branch (HFM-12),
Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852-
1448. Send two self-addressed adhesive labels to assist that office in
processing your requests. Persons with access to INTERNET may request
this document from ``[email protected].'' The document may
also be obtained by calling the CBER FAX Information System at 301-594-
1939 from a FAX machine with a touch tone phone attached or built in.
Submit written comments on the draft PTC document to the Dockets
Management Branch (HFA-305), Food and Drug Administration, rm. 1-23,
12420 Parklawn Dr., Rockville, MD 20857. Two copies of any comments are
to be submitted, except that individuals may submit one. Requests and
comments should be identified with the docket number found in brackets
in the heading of this document. The draft PTC document 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: Kathryn E. Stein, Center for Biologics
Evaluation and Research, Office of Therapeutics Research and Review/
Division of Monoclonal Antibodies (HFM-555), Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 301-402-
4606.
SUPPLEMENTARY INFORMATION: FDA is announcing the availability of a
draft PTC document entitled ``Points to Consider in the Manufacture and
Testing of Monoclonal Antibody Products for Human Use.'' The draft PTC
document reflects the considerable experience that has been gained
through review of submissions since 1987 and discussions that have
taken place at several national and international meetings. The draft
PTC document provides a discussion of topics that should be considered
in the development of monoclonal antibody products. At present, most
monoclonal antibody (mAb) products are produced by hybridoma cell lines
through immortalization of antibody-producing cells by chemically-
induced fusion with myeloma cells. In some cases, additional fusions
with other lines have created ``triomas'' and ``quadromas.'' CBER
anticipates an increase in recombinant and human antibodies in the
future. The principles reviewed by the draft PTC document may be
applied in general to all hybridoma and heterohybridoma generated
products, regardless of species of origin.
The draft PTC document details the approach that sponsors and
investigators should follow in product manufacturing and testing,
preclinical and clinical studies, and the information to be provided
for review and evaluation of clinical testing and licensing. The draft
PTC document describes the characterization of purified, unmodified mAb
which is essential for manufacturing control of product, determination
of potency and stability, and development of an appropriate clinical
development program. Special considerations for immunoconjugates
(monoclonal antibodies conjugated with toxins, drugs, radionuclides or
other agents) are addressed. The draft PTC document also details the
considerations for combination products. Issues addressed in the draft
PTC document include: (1) Quality control and product testing including
cell line qualification; (2) lot-to-lot quality control monitoring of
bulk lots and final product specifications; (3) stability of the
product; and (4) quantitation and removal of a known contaminant. The
draft PTC document also addresses issues related to manufacturing
changes, including those made either during clinical development or
subsequent to product approval. The draft PTC document discusses issues
relating to: (1) Preclinical studies including in vitro testing for
cross-reactivity; (2) preclinical pharmacology; (3) safety; and (4)
toxicity testing. With respect to clinical studies, the draft PTC
document discusses general study design for Phase 1, 2, and 3 studies,
clinical considerations involved in immunogenicity, dosimetry, and
imaging agents for cancer.
As with other PTC documents, FDA does not intend this draft PTC
document to be all-inclusive and cautions that not all information may
be applicable to all situations. The draft PTC document is intended to
provide information and does not set forth requirements. The methods
and procedures cited in the draft PTC document are suggestions. FDA
anticipates that sponsors and investigators may develop alternative
methods and procedures, and discuss them with FDA. CBER may find those
alternative methods and procedures acceptable. FDA recognizes that
advances will continue in the area of monoclonal antibodies and that
this document may become outdated as those advances occur. This PTC
document does not bind FDA and does not create or confer any rights,
privileges, or benefits on or for any private person, but is intended
merely for guidance.
Interested persons may submit written comments on the draft PTC
document to the Dockets Management Branch (address above). FDA
anticipates revising the draft PTC document periodically in response to
comments received or to reflect advancements in monoclonal antibody
therapies and products.
Dated: July 28, 1994.
Michael R. Taylor,
Deputy Commissioner for Policy.
[FR Doc. 94-18846 Filed 8-2-94; 8:45 am]
BILLING CODE 4160-01-F