Division of Pharmaceutical Science, Center for Drug Evaluation, Taipei, Taiwan, ROC; School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC.
Office of Executive Director, Center for Drug Evaluation, Taipei, Taiwan, ROC; School of Pharmacy, National Taiwan University, Taipei, Taiwan, ROC.
Regul Toxicol Pharmacol. 2018 Apr;94:33-39. doi: 10.1016/j.yrtph.2018.01.004. Epub 2018 Jan 9.
Generic drugs are accounted for majority of medicinal products. To reduce the unnecessary review for incomplete dossiers of generic drugs, Taiwanese government launched a refuse-to-file (RTF) process since 2017. The present study aimed to examine the outcome of RTF process by analyzing application characteristic, RTF rate and deficiencies found in the submitted dossiers. Descriptive analyses of administrative information, chemistry, manufacturing and controls, bioequivalence study, and comparative dissolution testing were presented during the first 6 months after the implementation of RTF policy. The results showed that the source of application was likely a determinant to the RTF outcome, i.e., foreign rather than domestic applications were more liable to be RTF. It is possibly that (i) RTF applications were mainly due to incomplete dossiers regarding bioequivalence study and comparative dissolution testing, and (ii) the studies (bioequivalence and dissolution) of domestic applications conducted locally are exempted from the RTF process because they are allowed to submit for review before generic drug applications. Finally, the dossier integrity appeared not improved during the period of analysis as the number of RTF did not reduce by month. Results of the present study may help pharmaceutical industry to improve the dossiers' quality by fixing the deficiencies of generic drug submission.
仿制药占药品的大部分。为了减少对仿制药不完整档案的不必要审查，台湾政府自 2017 年以来启动了拒绝备案（RTF）程序。本研究旨在通过分析申请特征、RTF 率和提交档案中发现的缺陷，来检验 RTF 程序的结果。在 RTF 政策实施后的头 6 个月，对行政信息、化学、制造和控制、生物等效性研究和比较溶出度测试进行了描述性分析。结果表明，申请来源可能是 RTF 结果的决定因素，即外国申请比国内申请更容易被 RTF。这可能是因为 (i) RTF 申请主要是由于生物等效性研究和比较溶出度测试的不完整档案，以及 (ii) 国内申请的研究（生物等效性和溶解）在当地进行，因为它们可以在仿制药申请之前提交审查，所以免于 RTF 程序。最后，由于 RTF 的数量并没有逐月减少，因此在分析期间档案的完整性似乎没有得到改善。本研究的结果可能有助于制药行业通过解决仿制药提交的缺陷来提高档案的质量。
