RESUMO
Immune globulin subcutaneous, human 20% solution (IGSC-C 20%, Xembify®)-a new 20% immunoglobulin (IgG) liquid product for subcutaneous (SC) administration-has been developed by Grifols. The IGSC-C 20% formulation is based on knowledge acquired from the formulation of Immune Globulin Injection (Human),10% Caprylate/Chromatography Purified (IGIV-C 10%, Gamunex®-C). The protein concentration was increased from 10% to 20% to provide a smaller volume for SC administration. The IGSC-C 20% manufacturing process employs the same caprylate/chromatography purification steps as IGIV-C 10%, with the addition of an ultrafiltration step so that the product can be formulated at a higher protein concentration. IGSC-C 20% has been produced at full industrial scale to support clinical studies and licensure. These batches were characterized using a comprehensive panel of analytical testing. The new IGSC-C 20% product maintains the same composition, neutralizing activity, purity, and quality characteristics found in IGIV-C 10%.
Assuntos
Imunoglobulina G , Humanos , Imunoglobulina G/química , Imunoglobulina G/isolamento & purificação , Injeções SubcutâneasRESUMO
A sudden, unprecedented failure of USP rabbit pyrogen tests for multiple 10% IGIV-C lots prompted a thorough investigation of the root cause for this phenomenon. All microbe-related testing, including Limulus amebocyte lysate test for endotoxin, proved negative, and no deficiencies were discovered in manufacturing. Plasma pool composition analysis revealed that a single plasma donor ("Donor Xâ³) was common to all pyrogenic IGIV-C lots and that as little as one unit of "Donor Xâ³ plasma (in a pool of â¼4500 units) was sufficient to cause IGIV-C lot failure in the USP rabbit pyrogen test. Whole plasma and Protein A-purified IgG from "Donor Xâ³ caused a temperature increase in rabbits; however, all IgG samples tested pyrogen-negative in two in vitro cell-based pyrogen tests. Flow cytometry showed that "Donor Xâ³ IgG bound strongly to rabbit white blood cells (WBC) but minimally to human WBC. Exclusion of "Donor Xâ³ plasma from manufacturing marked the end of IGIV-C lots registering positive in the USP rabbit pyrogen test. This failure of multiple 10% IGIV-C lots to pass the USP rabbit pyrogen test was demonstrated to be due to the highly unusual anti-rabbit-leukocyte specificity of IgG from a single donor.
Assuntos
Doadores de Sangue , Imunoglobulina G/imunologia , Imunoglobulinas Intravenosas/imunologia , Leucócitos/imunologia , Pirogênios/imunologia , Animais , Contaminação de Medicamentos/prevenção & controle , Endotoxinas/análise , Endotoxinas/imunologia , Humanos , Teste do Limulus/métodos , CoelhosRESUMO
Excess nitrogen and phosphorus ("nutrients") loadings continue to affect ecosystem function and human health across the U.S. Our ability to connect atmospheric inputs of nutrients to aquatic end points remains limited due to uncoupled air and water quality monitoring. Where connections exist, the information provides insights about source apportionment, trends, risk to sensitive ecosystems, and efficacy of pollution reduction efforts. We examine several issues driving the need for better integrated monitoring, including: coastal eutrophication, urban hotspots of deposition, a shift from oxidized to reduced nitrogen deposition, and the disappearance of pristine lakes. Successful coordination requires consistent data reporting; collocating deposition and water quality monitoring; improving phosphorus deposition measurements; and filling coverage gaps in urban corridors, agricultural areas, undeveloped watersheds, and coastal zones.