The emergence of biosimilar insulin preparations--a cause for concern?

Abstract

Several biopharmaceuticals, including insulin and insulin analogs, are, or shortly will be, off-patent, thereby providing an opportunity for companies to attempt to manufacture "copies" commonly referred to as biosimilars and also known as follow-on biologics. Reassurance that such copy biologics are equally safe and effective as the conventional products is essential. It is important for the clinician to consider what information is therefore necessary for such assurances. Biopharmaceuticals, produced from living organisms and manufactured by complex processes, differ in many respects from chemically derived drugs. The biological source materials and manufacturing processes for non-innovator biologics may differ considerably from those used for producing the innovator substance. Differences between innovator and non-innovator products can be identified analytically (e.g., batch-to-batch consistency, product stability along side clinical safety). This provides a strong argument for caution before automatic substitution of conventional products (e.g., insulin by biosimilars). Several non-innovator insulins, including insulin analogs (while still patent-protected), are already available in many countries. Many of these lack rigorous regulations for biosimilar approval and pharmacovigilance. Recently an application for a biosimilar recombinant human insulin was withdrawn by the European Medicines Agency because of safety and efficacy concerns. Therefore, every biosimilar insulin and insulin analog should be assessed by well-defined globally harmonized preclinical and clinical studies followed by post-marketing pharmacovigilance programs, in the interest of people with diabetes worldwide.

FIG. 1.

Analytical comparison of the insulin glargine copies (A) Basalin^®, (B) Glaritus^®, and (C) Basalog^® with the innovator product Lantus^® using reverse-phase high-performance liquid chromatography. As each glargine manufacturer has its own unique manufacturing process, the individual biotechnological production process leads to a specific analytical fingerprint of the final product that can be identified by the formation of characteristic insulin-related substances upon reverse-phase high-performance liquid chromatography separation. Total insulin-related substances detected in each chromatogram is below 1.5%, and each single insulin-related substance is below 1% of the total glargine amount. AU, absorption units.