Shifting paradigms: biopharmaceuticals versus low molecular weight drugs

Publication Type:

Journal Article


International Journal of Pharmaceutics, Volume 266, Number 1-2, pp. 3-16 (2003)



DOI Name (links to online publication)



biopharmaceuticals; biologicals; biogenerics; immunogenicity; pk-pd; safety evaluation; guidelines; lysozyme


Biopharmaceuticals are pharmaceutical products consisting of (glyco)proteins. Nowadays a substantial part of the FDA-approved drugs belong to this class of drugs. Biopharmaceuticals deserve special attention as they have a number of characteristics that set them aside from low molecular weight drugs.Their activity depends on their complicated shape based on secondary, tertiary and (sometimes) quaternary structures. These structures cannot be fully defined with our present set of analytical techniques and approaches for potency testing. They often are the same as (or closely resemble) endogenous proteins. This means that in safety testing and clinical test programs questions have to be addressed regarding species specific responses, selection of dosing schedules and route of administration, and the possible occurrence of immunogenicity. As the conformational structure of a protein is easily disturbed, formulation and handling of biopharmaceuticals needs special attention in order to optimize the therapeutic effect and minimize adverse reaction, among which immune responses.The issue of biogenerics is gaining more and more interest and different critical elements in the development of biogenerics are touched upon.In conclusion, biopharmaceuticals cannot be characterized fully in terms of their structure like low molecular weight drugs. The performance of biopharmaceuticals relies on strict production protocols and close monitoring of their activity in the clinical situation. 2003 Published by Elsevier B.V.