Vivir

Guidance for Industry
Monoclonal Antibodies Used as
Reagents in Drug Manufacturing

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
March 2001

Guidance for Industry
Monoclonal Antibodies Used as
Reagents in Drug Manufacturing
Additional copies are availablefrom:
Drug Information Branch, HFD-210
Center for Drug Evaluation and Research (CDER)
5600 Fishers Lane
Rockville, Maryland 20857
(Tel) 301-827-4573
(Internet) http://www.fda.gov/cder/guidance/index.htm
or
Office of Communications
Training and Manufacturers Assistance, HFM-40
Center for Biologics Evaluation and Research (CBER)
1401 Rockville Pike
Rockville, Maryland 20852-1448
(Fax)888-CBERFAX or 301-827-3844
(Voice Information) 800-835-4709 or 301-827-1800
(Internet) http://www.fda.gov/cber/guidelines.htm

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
March 2001

TABLE OF CONTENTS

I.INTRODUCTION..................................................................................................................................................................1

II.

BACKGROUND....................................................................................................................................................................2

III.

PRODUCTION OF MONOCLONAL ANTIBODY REAGENTS.................................................................................3

IV.

MONOCLONAL ANTIBODY REAGENTS IN DRUG MANUFACTURING..............................................................4

A.
B.
V.

SPECIFICATIONS FOR MONOCLONAL ANTIBODY REAGENTS........................................................................5
A.
B.

VI.

PURIFICATION OF DRUG S UBSTANCE............................................................................................................................ 4
COMPARABILITY............................................................................................................................................................... 5

TESTING OF UNCONJUGATED MONOCLONAL ANTIBODY REAGENTS ....................................................................... 6TESTING OF MONOCLONAL ANTIBODY REAGENTS LINKED TO S OLID S UPPORT .................................................. 6
STABILITY OF MONOCLONAL ANTIBODY REAGENTS .......................................................................................7

REFERENCES..................................................................................................................................................................................8

GUIDANCE FOR INDUSTRY1
Monoclonal Antibodies Used as Reagents in Drug Manufacturing

This guidance represents the Food and Drug Administration's (FDA's) current thinking on this
topic. It does not create or confer any rights for or on any person and does not operate to bind
FDA or the public. An alternative approach may be used if such approachsatisfies the
requirements of the applicable statutes and regulations.

I.

INTRODUCTION

This guidance is intended to provide recommendations to sponsors and applicants on the use of
monoclonal antibodies (mAbs) as reagents in the manufacture of drug substances2 that are regulated by
the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and
Research(CBER). The guidance focuses on the chemistry, manufacturing, and control (CMC) issues
that should be addressed in new drug applications (NDAs), abbreviated new drug applications
(ANDAs), biologics license applications (BLAs), supplements to these applications, or investigational
new drug applications (INDs).
This document presents issues associated with and recommendations on the documentation to...