Bioequivalence of Two Subcutaneous Pharmaceutical Products of Interferon Beta 1a

DI GIROLAMO GUILLERMO; KAUFFMAN MARCELO; GONZALEZ ELISEO; PAPOUCHADO MARIANA; STERIN-PRYNC AIDA; DIEZ ROBERTO

ARZNEIMITTEL FORSCHUNG DRUG RESEARCH

ECV-EDITIO CANTOR VERLAG MEDIZIN NATURWISSENSCHAFTEN

Año: 2008 vol. 58 p. 193 - 198

0004-4172

Blastoferon®, in the following referred to as the test product, is a pharmaceutical product of interferon beta 1a (CAS 220581- 49-7) currently marketed as a biosimilar to the innovator interferon beta 1a product (referred to as the reference product). Pharmacokinetics and pharmacodynamics assays are critically relevant to demonstrate similarity between biopharmaceuticals. 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 Tmax of 4 h (4–6) and a Cmax of 3.69 (3.27–4.41) IU × ml-1. In the relative BA study, values for the test product were: median Tmax of 3 h (2–18), Cmax of 5.39 (4.99–6.31) IU x ml-1, AUC (0-72) of 142.86 (134.16–190.15) IU × h × ml-1 and AUC(0-infinity) of 190.95 (174.23– 303.13) IU × h × ml-1. The corresponding values for the innovator product were: Tmax of 3 h (1–24), Cmax of 4.44 (4.12–5.40) IU x ml-1, AUC(0-72) of 128.77 (121.18– 170.92) IU × h × ml-1 and AUC(0-infinity) of 192.61 (183.04–286.46) IU × h × ml-1. The AUC(0-72) ratio was 111 % (CI 90 %: 106– 116), the AUC(0-infinity) was 99 % (CI 90 %: 92–107) and the Cmax ratio was 121 % (CI 90 %: 112–131). IFNB1a 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 IFNB1a for both pharmaceutical products.