Biosimilars: recent developments

Abstract

Biopharmaceuticals are recombinant protein drugs which are produced by biotechnology. The availability of such molecules has revolutionised the way we treat many diseases. However, the patents for many originator biopharmaceuticals are expiring, and a new generation of follow-on molecules, termed "biosimilars", are under development. Health care providers perceive biosimilars to be cheap replacements for originator drugs such as recombinant human erythropoietin and human growth hormone. However, concerns have been raised about the comparability of biosimilars with originator products especially in light of the complex manufacturing process required to produce biopharmaceuticals. The complexity of protein molecules renders it impossible to produce identical copies; this in turn raises questions on the safety of follow-on biosimilar products, particularly with respect to immunogenicity. This review briefly outlines the process of biopharmaceutical production, potential problems that can arise from their long-term use in patients, and the issues facing regulatory bodies as they look to institute guidelines for new biosimilar molecules.

Immunogenicity, toxicology, pharmacokinetics and pharmacodynamics of growth hormone ligand–receptor fusions

“…The immunogenicity of protein therapeutics can be influenced by many factors, including the amino acid sequence, the glycosylation patterns, degradation of the protein, aggregation or aberrant folding of the protein, chemical modification (such as oxidation), the processing of the protein, product formulation and even the route of administration [20]. The GH LR-fusion proteins were designed to minimize the immunogenic proclivity of the therapeutic protein.…”

Biologics, Biosimilars, Intended Copies and the Era of Competitive Medicine

“…Even minute changes in the process could have profound effects on the biological activity and safety profile of the final product. 27 The manufacturing process begins with the construction of the master cell bank (Figs. 1-3).…”

Medicamentos Biotecnológicos: Requisitos Exigidos para el Desarrollo y Aprobación de Biosimilares

“…Además, algunos parámetros como la estructura tridimensional, cantidad de variantes ácido-base o modificaciones post-traducción tales como el perfil de glicosilación pueden alterarse de forma significativa debido a cambios, que inicialmente se consideran "menores" en el proceso de fabricación (Zopf y Vergis, 2002;Covic y Kuhlman, 2007;Roger y Mikhail, 2007) . Por lo tanto, el perfil de seguridad-eficacia de estos productos depende en gran medida de la robustez y la monitorización de los aspectos de calidad (Zúñiga y Calvo, 2009b).…”