Identification and quantitation of impurities and residu

摘要：该项目的目标是开发和验证生物制品中化学杂质和残留制造剂的方法，这些方法的存在可能会影响产品的安全性或有效性。这些包括：1)疫苗中用作灭活剂或偶联剂的残留戊二醛，2)花粉致敏提取物和致敏源材料中的残留四氯乙烯，3)粗致敏提取物和致敏原贴片试验材料中的非活性成分，以及4)免疫球蛋白产品中的抗病毒剂，不活性。

Summary: The objectives of this project are to develop and validate methodologies for chemical impurities and residual manufacturing agents in biological products whose presence may affect product safety or efficacy. These include: 1) residual glutaraldehyde used as inactivating or conjugating agent in vaccines, 2) residual tetrachloroethylene in pollen allergenic extracts and allergenic source materials, 3) inactive components of crude allergenic extracts and allergen patch test materials and 4) an antiviral agent, inactine, in immune globulin products. Current work in progress, or that performed in the past year includes: 1) The development and validation of methods for the determination of tetrachloroethylene, used in the processing of pollen source materials for allergenic extracts. A purge-and-trap gas chromatographic method for tetrachloroethylene in allergenic extracts has been developed and validated, data has been obtained for a representative sampling of final products. The determination of this same compound in allergenic source materials by gas chromatography/mass spectrometry is in the process of validation, interim data on a representative sampling of pollen source materials have been collected. 2) An HPLC method for the determination of glutaraldehyde, involving pre-column derivatization with p-nitrobenzyl-hydroxylamine and UV detection has been developed and validated as a limits test at 100ppb. 3) An HPLC ion-exchange and post-column derivatization/fluourescence procedure for the determination of inactine in immune globulins was transfered and modified. A lengthy attempt was made to qualify a manufacturer's procedure, which required extensive modification before successful detection at the required limit of 1 part-per-billion was accomplished. 4) A recently acquired ion-trap HPLC/mass spectrometer will be used along with gas chromatography/mass spectrometry to develop a general procedure for impurities screening in a variety of products as well as the characterization of low-molecular weight compounds in allergenic extracts and allergen patch test products.