RESUMO
BACKGROUND: Biosimilars must meet stringent regulatory requirements, both at the time of authorization and during their lifecycle. Yet it has been suggested that divergence in quality attributes over time may lead to clinically meaningful differences between two versions of a biologic. Therefore, this study investigated the batch-to-batch consistency across a range of parameters for released batches of the etanercept biosimilar (SB4) and infliximab biosimilar (SB2). METHODS: SB4 (Benepali®) and SB2 (Flixabi®) were both developed by Samsung Bioepis and are manufactured in Europe by Biogen at their facility in Hillerød, Denmark. A total of 120 batches of SB4 and 25 batches of SB2 were assessed for consistency and compliance with specified release parameters, including purity, post-translational glycosylation (SB4 only), protein concentration, and biological activity. RESULTS: The protein concentration, purity, tumor necrosis factor-α (TNF-α) binding, and TNF-α neutralization of all batches of SB4 and SB2 were within the strict specification limits set by regulatory agencies, as was the total sialic acid (TSA) content of all batches of SB4. CONCLUSIONS: Quality attributes of SB4 and SB2 batches showed little variation and were consistently within the rigorous specifications defined by regulatory agencies.
Assuntos
Anti-Inflamatórios não Esteroides/normas , Antirreumáticos/normas , Medicamentos Biossimilares/normas , Etanercepte/normas , Tecnologia Farmacêutica/normas , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/imunologia , Anti-Inflamatórios não Esteroides/farmacologia , Antirreumáticos/química , Antirreumáticos/farmacologia , Medicamentos Biossimilares/química , Medicamentos Biossimilares/farmacologia , Etanercepte/química , Etanercepte/farmacologia , Europa (Continente) , Glicosilação , Humanos , Infliximab/química , Infliximab/farmacologia , Ácido N-Acetilneuramínico , Controle de Qualidade , Tecnologia Farmacêutica/métodos , Fator de Necrose Tumoral alfaRESUMO
The chromosomal locus NP_636946 of Xanthomonas campestris DSM 3586 (ATCC 33913) which was earlier presumed to encode a quinoprotein glucose dehydrogenase has been cloned, expressed in Escherichia coli and the recombinant enzyme has been characterised. It was found to have no glucose dehydrogenase activity but to be active on many different polyols and diols, aliphatic alcohols, certain aldonic acids and amino-sugars. The product of D: -gluconic acid oxidation was 5-keto-D: -gluconic acid. The enzyme differs from polyol/gluconate dehydrogenases found in Gluconobacter by its single-chain architecture, different substrate specificity and much higher (20- to 30-fold) expression level in E.coli.
