RESUMO
Recombinant human granulocyte-colony stimulating factor (filgrastim) is a therapeutic protein used primarily to reduce incidence and duration of severe neutropenia and its associated, and serious, complications. We have developed a biosimilar filgrastim (Hospira filgrastim; Nivestim) designed to be comparable to Amgen filgrastim (Neupogen). An extensive characterization study assessed the physiochemical similarity of Hospira filgrastim to Amgen filgrastim. Both drugs were supplied in 1 ml glass, single-use, prefilled syringes (five batches of each product at 480 microg/0.5 ml and one batch of each product at 300 microg/0.5 ml). Samples were evaluated using state-of-the-art analytical methods (validated in accordance with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use or Pharmeuropa guidelines) to determine physicochemical properties, molecular characteristics, purity and biological activity. Samples were compared after long-term storage at 2-8 degrees C and storage at 40 degrees C (stress conditions) to evaluate their degradation impurity profiles. Hospira filgrastim and Amgen filgrastim were shown to have similar physicochemical properties, molecular characteristics, purity and biological activity. No significant differences in product-related impurities were recorded between Hospira filgrastim and Amgen filgrastim following storage for 12 weeks under stress conditions. These data show that the physicochemical profile of Hospira filgrastim is similar to that of Amgen filgrastim.
Assuntos
Medicamentos Genéricos/farmacocinética , Medicamentos Genéricos/normas , Fator Estimulador de Colônias de Granulócitos/farmacocinética , Fator Estimulador de Colônias de Granulócitos/normas , Sequência de Aminoácidos , Fenômenos Químicos , Cromatografia Líquida de Alta Pressão , Contaminação de Medicamentos , Medicamentos Genéricos/química , Medicamentos Genéricos/metabolismo , Eletroforese em Gel de Poliacrilamida , Filgrastim , Fator Estimulador de Colônias de Granulócitos/química , Fator Estimulador de Colônias de Granulócitos/metabolismo , Humanos , Metaboloma , Dados de Sequência Molecular , Processamento de Proteína Pós-Traducional , Proteínas Recombinantes , Padrões de Referência , Equivalência TerapêuticaRESUMO
The repair of double strand breaks after gamma-irradiation in wild-type Escherichia coli lysogenic for lambda cI857 red3 is more efficient when lambda Gam protein is present. This phenomenon, called gam dependent radioresistance, requires the interaction of RecBCD enzyme and Gam protein. We compared cell survival after gamma-irradiation in wild-type and mutant lysogens with and without induction of Gam by transient heat treatment of the cells (6 min, 42 degrees C). The main conclusions are: (1) the RecBCD-Gam pathway of recombination repair is similar but not equivalent to RecBCD, a pathway operating in recD mutants; (2) the RecBCD-Gam pathway is dependent on recJ, recQ and recN gene products and it is proposed that the RecBCD-Gam complex has ability to load RecA protein onto single strand DNA.
