Module 9 2021

22/03/2021

Monoclonal antibodies (mAbs) and related formats

 Examples of some of the more common mAb formats..…..

Antigen binding site

Heavy chain

Light chain

Fc Region

Bispecific antibody

Figure modified from Schweizera et al (2014). European Journal of Pharmaceutics and Biopharmaceutics, 88, Pages 291-309

Preclinical testing of Biologics – March 22

nd 2021

The Organisation for Professionals in Regulatory Affairs

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Preclinical Safety of Biologics : Important  NBEs are not just “large” small molecules

Characteristics

Biologics

Small Molecules Less than 500 daltons

Molecular Weight

Greater than 1000 daltons (monoclonal antibody = 150,000 daltons) Typically on target as a result of exaggerated pharmacology Pharmacology often restricted to one species and often primate only  MUST be demonstrated Typically intravenous or sub-cutaneous

Toxicity

On or off target

Species specificity

Pharmacology and any off-target toxicity are usually species independent  Rodent + Non-rodent

Route of Admin

Typically Oral

Absorption, Distribution, Metabolism, Excretion

Long half-life in blood Usually catabolized like other proteins

Short half-life (<24hr) May have one or more metabolites which may be active and/or have safety issues

Immunogenicity (Antibodies against the drug may impact efficacy)

Immunogenicity often observed • Needs monitoring in nonclinical and clinical studies

Rare

Drug product

Simpler formulations, usually a solution Complex formulation (tablet, nanoparticle, suspension)

Preclinical testing of Biologics – March 22 nd 2021

The Organisation for Professionals in Regulatory Affairs

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