RESUMEN
A robust, economical process should leverage proven technology, yet be flexible enough to adopt emerging technologies which show significant benefit. Antibody and Fc-fusion processes may capitalize on the high selectivity of an affinity capture step by reducing the total number of chromatographic steps to 2. Risk associated with this approach stems from the potentially increased time frame needed for process development as well as unforeseen changes in impurity profile during first scale-up of drug substance (DS) for animal toxicology and clinical phase I trials (FIH) production, which could challenge a two-step process to the point of failure. Two different purification strategies were pursued during process development for an FIH process of a dAB-Fc fusion protein. A two-step process was compared to a three-step process. The two-step process leveraged additives to maximize impurity reduction during affinity capture. While wash additives in combination with a mixed mode chromatography met all impurity reduction requirements, HCP levels were still higher as compared to the three-step process. The three-step process was implemented for manufacture of clinical material to mitigate risk.
Asunto(s)
Cromatografía Liquida/métodos , Fragmentos Fc de Inmunoglobulinas/aislamiento & purificación , Proteínas Recombinantes de Fusión/aislamiento & purificación , Animales , Células CHO , Cricetulus , Fragmentos Fc de Inmunoglobulinas/genética , Proteínas Recombinantes de Fusión/genéticaRESUMEN
The seroprevalence of antibody to severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) in cohorts of health care workers (HCWs) with subclinical infection in SARS and non-SARS medical wards was 2.3% (3 of 131 HCWs) and 0% (0 of 192 HCWs), respectively. Rates for clinical SARS-CoV infection among 742 HCWs on these wards were highest among nurses (11.6%) and health care assistants (11.8%), indicating that these occupations are associated with the highest risks for exposure.
Asunto(s)
Transmisión de Enfermedad Infecciosa de Paciente a Profesional , Síndrome Respiratorio Agudo Grave/epidemiología , Síndrome Respiratorio Agudo Grave/transmisión , Anticuerpos Antivirales/sangre , Personal de Salud , Hong Kong , Unidades Hospitalarias , Humanos , Exposición Profesional , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , Estudios SeroepidemiológicosRESUMEN
Analysis of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) isolates in Hong Kong by use of a combination of antibiogram typing, serotyping, multilocus sequence typing, and pulsed-field gel electrophoresis indicated that the dissemination of PNSP was the result of the spread of international clones: variants of the Spain(23F)-1 or Spain(6B)-2 clones were the predominant PNSP isolates from 1994 to 1997 and remained so, but Taiwan(19F)-14 and Taiwan serotype 6B clones were disseminated in Hong Kong in 1999 and 2000. Concomitant changes in antibiotic susceptibility profiles, with the rate of susceptibility to chloramphenicol rising from 10% in the period from 1994 to 1997 to 31% (P < 0.001) in 1999 and 2000, were noted to accompany the shift of clones.