Production and manufacturing of biosimilar insulins: implications for patients, physicians, and health care systems
Martin K Kuhlmann,1 Andrea Schmidt2
1Department of Internal Medicine–Nephrology, Klinikum im Friedrichshain, Berlin, Germany; 2Sanofi, Frankfurt, Germany
Abstract: More than 380 million people worldwide have diabetes, a disease that accounts for almost US$550 billion in global health care spending. The majority of patients with diabetes will require insulin replacement as part of their therapeutic regimen. In some countries, the approaching patent expiry dates for the long-acting insulin analog insulin glargine mean there is increasing interest in the potential of biosimilar insulins. However, the production and manufacturing of biosimilar insulins is a proprietary, complex, multistep process in which each stage can potentially introduce variability, possibly leading to adverse clinical and safety outcomes. Thus, marketing authorization in countries in which stringent regulatory requirements are in place requires manufacturers to demonstrate similarity in pharmacokinetic/pharmacodynamic properties, clinical efficacy, and adverse event and immunogenicity profiles, as well as provide proof of the quality of the production process between the biosimilar and the reference insulin product. A risk management plan and pharmacovigilance program may also be needed for the approval process. Regulatory guidelines for the introduction of biosimilar insulins differ between countries but are most developed for the European Union. As of the date of submission of this manuscript (April 30, 2014), no insulin or insulin analogs have received marketing authorization based on the European Union standards established for biosimilars; however, European Medicines Agency approval of a biosimilar glargine insulin is awaited for the end of 2014. In recent years several copies of the long-acting insulin glargine have been brought onto the market in countries such as India, the People’s Republic of China, Pakistan, Mexico, and Kenya without following a biosimilar pathway. In this article, we review the key issues associated with the production and manufacturing of biosimilar insulins, including a European regulatory perspective on manufacturing guidelines designed to ensure clinical efficacy and patient safety.
Keywords: biosimilar insulin, follow-on insulin, regulatory guidelines, diabetes
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