[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