蛋白质柱层析分离纯化验证现状1.docx

Industry Perspective on the Validation of Column-Based Separation Processes for the Purification of Proteins蛋白质柱层析分离纯化验证现状Foreword前言The purpose of this document is to outline some of the significant issues related to the validation of columnbased separation processes used in the purification of proteins produced by recombinant DNA (rDNA), hybridoma technology, or peptide synthesis. While validation of these processes has been identified as a first priority by the PDA Biotechnology Task Force, the issues raised in certain sections of this document may have broader applications, including processes for non-protein pharmaceutical products purified by HPLC, as well as protein pharmaceuticals which are not produced by rDNA, hybridoma, or peptide synthesis technologies. 这个文件的目的是概述一些关于重组DNA（rDNA），杂交瘤技术，或多肽合成过程中有重大意义的柱分离纯化验证。当这些过程的验证已作为PDA生物技术工作团队的首要任务时，本文件中所提及的问题可能有更广泛的应用，包括利用高效液相色谱技术纯化非蛋白医药产品，又包括不通过rDNA，杂交瘤，或肽合成技术生产的蛋白质药品。While column-based separations are key purification techniques in the production of recombinant proteins and monoclonal antibodies, little has been written regarding the validation of these processes. In general, process validation is the assurance that product quality is derived from careful attention to a number of factors, including process design, selection and use of quality parts and materials, and control of the process through appropriate in-process and end-product testing. In May 1987, the Center for Drugs and Biologics and the Center for Devices and Radiological Health of the Food and Drug Administration published the Guideline on General Principles of Process Validation. While this guideline is useful, it does not include all of the specific elements required in the validation of a manufacturing process. Therefore, the PDA established the Biotechnology Task Force on Purification and Scale-up to develop a practical guide for the validation of column-based separations used in the manufacture of proteins intended for use as therapeutic or diagnos