重组蛋白质/抗体药物的HCP的覆盖率问题

dcp110

今早看到微信群有人问HCP的覆盖率问题“采用Elisa评估HCP 总量时，需要考虑HCP的ELISA抗体的覆盖率（Coverage），这个覆盖率一般需要大于多少啊?还是说不用管，只要测出覆盖率，然后折算总量?”

有人回答是“和CBERs交流了解的信息，最差不能低于50%, 但通常的期望是70%。我没有具体的出处，你看一下USP通则1132和后面的参考资料中是不是有。”

个人看法，目前国内国外对HCP覆盖率没有明确规定需要达到多少，一般在IND时用的都是商业化试剂盒，这时也需要对覆盖率进行简单的验证，也不能太低，一般是50%以上；到临床后期，需要建立专属试剂盒，关于专属试剂盒怎么制备，目前工业界也有争议，BLA时的HCP覆盖率应该达到多少，这个也没有明确规定，但个人认为应该不低于50%。

呼伦拧拧

2014年，1132发布的时候，曾经提到过一点，Numerical 'coverage' values have technical limitations and a general lack of standardization for many variables. 1. currently the range of results obtained by the same company with the same reagents challenges the validity of this as a quantitative approach.2 for these reasons, 1132 chapter does not include a minimum % coverage value

呼伦拧拧

USP 1132 一段关于 coverage的描述 “Show that a broad range of HCPs in the calibration standard is recognized (i.e., that the coverage of the HCP population is adequate). Coverage is evaluated for at least the capture antibodies using 2-D gel Western blots or immunoaffinity fractionation of the total HCP population by immobilizing the anti-HCP antibodies on a column. In addition it is recommended to test the coverage of the detection antibody if different coating and detection antibodies are used. The benefits and limitations of using either 2-D gels or immunoaffinity fractionation to demonstrate coverage is discussed more fully below. Whichever method is used, the extent of coverage must be addressed in qualifying the immunochemical reagents. ”

小金库

感谢分享。