Related Experiment Video
Updated: May 9, 2026
11:02
Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
Published on: September 14, 2018
Formulation development of antibody-drug conjugates
William J Galush1, Aditya A Wakankar
1Early Stage Pharmaceutical Development, Genentech Inc., South San Francisco, CA, USA.
Methods in Molecular Biology (Clifton, N.J.)
|August 6, 2013
Summary
Developing antibody-drug conjugates (ADCs) requires considering drug-to-antibody ratio and drug stability. Understanding ADC stability differences from conventional antibodies is key for effective formulation selection.
Area of Science:
- Biopharmaceutical Formulation
- Antibody-Drug Conjugate (ADC) Development
- Analytical Chemistry
Background:
- Antibody-drug conjugates (ADCs) are complex therapeutics combining monoclonal antibodies with potent small-molecule drugs.
- Formulation of ADCs presents unique challenges compared to conventional antibody therapeutics due to the conjugated drug moiety.
- Key attributes like drug-to-antibody ratio (DAR) and drug stability significantly impact ADC efficacy and safety.
Purpose of the Study:
- To highlight the distinct considerations for ADC formulation development.
- To emphasize the importance of analytical characterization for ADC stability.
- To guide the selection of appropriate formulations for ADCs.
Main Methods:
- Review of formulation principles for biologics.
- Analysis of specific challenges introduced by drug conjugation.
- Application of advanced analytical techniques to assess ADC attributes.
- Comparative stability studies between ADCs and conventional antibodies.
Main Results:
- ADC formulation requires evaluation of drug-related attributes beyond antibody characteristics.
- Drug-to-antibody ratio (DAR) and the stability of the conjugated drug are critical parameters.
- Differences in stability profiles between ADCs and conventional antibodies necessitate tailored formulation strategies.
Conclusions:
- Successful ADC formulation relies on a comprehensive understanding of both antibody and drug properties.
- Utilizing an expanded analytical toolkit is essential for characterizing ADCs.
- Tailored formulation approaches, informed by stability data, are crucial for optimizing ADC product performance.
Related Concept Videos
01:14Phase II Conjugation Reactions: Overview
Conjugation, a key component of phase II biotransformation reactions, is a vital process in drug detoxification. It involves transferring endogenous substances like glucuronic acid, sulfate, and glycine to drugs or their metabolites formed in phase I reactions. These conjugation reactions, often catalyzed by specific enzymes, transform potentially harmful metabolites into inactive, water-soluble forms easily excreted in urine or bile. By enhancing polarity and eliminating pharmacological...
01:14Drug Metabolism: Phase II Reactions
Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
01:19Phase II Reactions: Sulfation and Conjugation with α-Amino Acids
Sulfation and α-amino acid conjugation are two critical biotransformation reactions in drug metabolism. Sulfation, a phase II biotransformation reaction, involves adding a polar sulfate group to a drug, enhancing its water solubility and promoting excretion. This process can either co-occur with or occur independently of glucuronidation. Nonmicrosomal sulfotransferase enzymes catalyze the process. The reaction involves 3'-phosphoadenosine-5'-phosphosulfate or PAPS coenzyme activation, sulfur...
01:22Biopharmaceutical Factors Influencing Drug Product Design: Overview
Rational drug product design integrates knowledge of the drug’s physicochemical properties, formulation components, manufacturing techniques, and intended route of administration. Each factor influences the drug’s performance, including how it is released, absorbed, and eliminated in the body.The physicochemical properties of a drug—such as solubility, stability, and particle size—affect its compatibility with excipients and the choice of dosage form. Excipients, though pharmacologically...
01:31Hybridoma Technology
Hybridoma technology is used for the large-scale production of monoclonal antibodies. Monoclonal antibodies bind to only a single antigenic determinant or epitope. Such antibodies are used in research, diagnostics, and disease therapy. The hybridoma technology established in 1975 by Georges Köhler and Cesar Milstein was awarded the Nobel Prize in Medicine in 1984 for revolutionizing research and therapy.
Hybridoma Selection
Commonly used fusion techniques — electroporation, polyethylene glycol...
Hybridoma Selection
Commonly used fusion techniques — electroporation, polyethylene glycol...
01:10Antibody Structure
Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...