纳米药物开发的监管：化学制造和控制角度的法规解析（英文）

Regulatory Perspective of the CMC Considerations for Nanodrug Development

与常规药物相比,纳米药物具有几个优点,包括更好的功效、更低的毒性和更好的药代动力学性质。在过去的10年中,纳米医学的快速发展成功地将纳米药物从单纯的概念转变为具有各种设计特性的实物,并且一些纳米药物已成功上市。本文简要回顾了目前常用的纳米药物开发方法、目前已经批准的纳米药物以及美国FDA关于纳米药物开发的现行监管指南。目前研究的纳米药物类型包括脂质体纳米药物、聚合物纳米药物、纳米晶体药物、无机纳米药物、胶束纳米药物和蛋白质纳米药物。本文详细介绍了几种批准上市的纳米药物的适应证、给药途径和活性成分。对于纳米药物开发的监管,美国FDA最近公布了2份重要的指南草案:一是2017年出版的“工业指南:含有纳米材料的药品,包括生物制品”,二是2018年发布的“工业指南:脂质体药物化学、制造和控制;人体药代动力学和生物利用度;标签文档”。本文对这2个指南(特别是从化学制造和控制的角度)进行了详细解读。

Compared to the conventional drugs,nanodrugs have several advantages,including better efficacy,lower toxicity,and better pharmacokinetic properties.The rapid evolvement of nanomedicine in the past decade has successfully conveyed nanodrug from a mere concept to some products with various designed characteristics,and some have been successfully approved.This paper gives a brief review of the currently available approaches for nanodrug development,the previously approved nanodrugs,and the current regulatory guidance from the US FDA regarding the development of nanodrugs.Right now,most intensively studied types of nanodrugs are liposomes,polymeric nanocarriers,nanocrystals,inorganic nanocarriers,micelles,and protein nanodrugs.Detailed introduction of several approved nanodrugs are reviewed regarding their indications,routes of administration,and active ingredients.Regarding the regulatory perspective of the development of nanodrugs,the US FDA recently published two important draft guidance.One is“Guidance for Industry:Drug Products,Including Biological Products,that Contain Nanomaterials”published in 2017,and the other is“Guidance for Industry:Liposome Drug Products Chemistry,Manufacturing,and Controls;Human Pharmacokinetics and Bioavailability;and Labeling Documentation”published in 2018.Detailed interpretations of these two guidance,especially in the perspective of chemistry manufacturing and controls(CMC),are provided in this paper.