Bio equivalence of Two Subcutaneous Pharmaceutical Products of Interferon Beta la

Abstract

Blastoferon®, in the following referred to as the test product, is a pharmaceutical product of interferon beta la (CAS 220581-49-7) currently marketed as a biosimilar to the innovator interferon beta la product (referred to as the reference product). Pharmacokinetics and pharmacodynamics assays are critically relevant to demonstrate similarity between biopharma-ceuticals. The aims of the present study were to investigate the bioavailability (BA) of the test product (either absolute or relative to the innovator product) and to compare the extent of increase of neopterin concentration following administration of either product. Two studies were performed: initially, an absolute BA assay with i.V. and s.c. injection of test product to 12 healthy subjects. Second, a formal relative BA study with s.c. injections of 88 μg of both products to 24 healthy volunteers. Blood samples for pharmacokinetic and pharmacodynamic profiling were drawn at different intervals after injection. Interferon beta (IFNB) concentrations were determined by ELISA. In the absolute BA study, a single s.c. dose of 44 μg of the test product resulted in a median bioavailable fraction of 29%, a median T_max of 4 h (4–6) and a C_max of 3.69 (3.27–4.41) IU · ml⁻¹.

In the relative BA study, values for the test product were: median T_max of 3 h (2–18), C_max of 5.39 (4.99–6.31) IU · ml⁻¹, AUC_(0–72) of 142.86 (134.16–190.15) IU 9 h ml¹ and AUC_{(0–infinity)} of 190.95 (174.23–303.13) IU 0 h ml⁻¹. The corresponding values for the innovator product were: T_max of 3h (l-24),C_max of 4.44 (4.12–5.40) IU I ml⁻¹, AUC_(0–72) of 128.77 (121.18–170.92) IU 7 h ml⁻¹ and AUC_(0-infinity) of 192.61 (183.04–286.46) IU 8 h h ml⁻¹. The Alicia ratio was 111% (CI 90%: 106–116), the AUC(_0-infinity) was 99% (CI 90%: 92–107) and the C_max ratio was 121% (CI 90%: 112–131). IFNBla increased neopterin levels in both studies. Both products induced side-effects commonly reported for IFN with no serious adverse events. This study presents pharmacokinetics parameters of the test product and demonstrates similar bioavailability of IFNBla for both pharmaceutical products.

Key words

Blastoferon®, bioequivalence, pharmacokinetics - CAS 220581-49-7 - Immunomodulators - Interferon beta la

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