Cancer and Metastasis Reviews

, Volume 24, Issue 4, pp 569–584 | Cite as

Development and regulation of monoclonal antibody products: Challenges and opportunities

  • Wendy C. Weinberg
  • Michelle R. Frazier-Jessen
  • Wen Jin Wu
  • Andrea Weir
  • Melanie Hartsough
  • Patricia Keegan
  • Chana Fuchs


An increasing number of monoclonal antibodies for cancer diagnosis and treatment are in clinical use and in the development pipeline, with more expected as new molecular targets are identified. As with all drugs, product quality, an appropriate pre-clinical pharmacology-toxicology testing program, and well-designed clinical trials are essential for a successful drug development program. However, protein products such as monoclonal antibodies present unique regulatory concerns. The derivation from biological sources as well as the constantly evolving technologies utilized to develop these products demands continuous appraisal of safety concerns, even while the accumulated experience with these protein products has facilitated their safety evaluations. Because of the complex nature of these products and their inherent heterogeneity, a mechanistic understanding of the mode of action along with careful attention to product design and manufacture are critical to assuring a safe, effective and consistent product. Protein products may be highly species specific, thus pharmacologically relevant animal models are an important component in accurately assessing pre-clinical safety and establishing initial dosing. Furthermore, the immunogenicity of protein products can impact its safety profile, dose exposure, and efficacy. Mechanistic insight should form the basis of biological assays used for monitoring efficacy, safety, lot-to-lot consistency and manufacturing changes. The inherent uniqueness of each product necessitates a flexible case-by-case approach for biologics review that is based on a strong scientific understanding of relative risks. This review will provide an overview of approaches used in the development of antibody-based cancer therapeutics and the scientific basis of regulatory reviews.


monoclonal antibodies Investigational New Drug (IND) cancer therapy Biologics License Application (BLA) clinical trials immunogenicity 



Non-Hodgkins Lymphoma


monoclonal antibody


Investigational New Drug application


Food and Drug Administration


antibody dependent cell mediated cytotoxicity


complement dependent cytotoxicity




human anti-mouse antibody


Code of Federal Regulations


Points to Consider


International Conference on Harmonisation


infectious prion protein


Biologics License Application


Prior Approval Supplement


carcinoembryonic antigen


FDA Modernization Act


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Wendy C. Weinberg
    • 1
  • Michelle R. Frazier-Jessen
    • 1
  • Wen Jin Wu
    • 1
  • Andrea Weir
    • 2
  • Melanie Hartsough
    • 2
  • Patricia Keegan
    • 2
  • Chana Fuchs
    • 1
  1. 1.Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical ScienceCenter for Drug Evaluation and Research, Food and Drug AdministrationBethesda
  2. 2.Division of Biologic Oncology Products, Office of Oncology, Office of New DrugsCenter for Drug Evaluation and Research, Food and Drug AdministrationRockville

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