Tyner Katherine, Sadrieh Nakissa
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Methods Mol Biol. 2011;697:17-31. doi: 10.1007/978-1-60327-198-1_3.
The Food and Drug Administration (FDA) does not, as yet, have specific guidances for products containing nanoscale materials. As announced in the report issued by the FDA Nanotechnology Task Force (July 2007), however, there are recommendations to various centers within the FDA to develop guidances for industry. Regardless of the lack of explicit FDA guidances, there are therapeutics currently on the market containing nanoscale materials, and additional novel nanomaterial-containing therapeutics are being developed with the hopes of being submitted for regulatory review and approval. While, for the most part, these novel nanomaterial-containing products are being evaluated using the same regulatory requirements as products that do not contain nanomaterials, it is increasingly evident that at least in the area of characterization of nanomaterials used in drug products, there may be areas where special focus is needed. Specific areas include the validity of applying small molecule principles and methodologies to nanomaterial-containing products, the effects the nanomaterial will impart to the rest of the formulation (or vice versa), and how the physicochemical properties may be impacted by biological settings. Similarly, for safety evaluation, biodistribution studies will be at the core of any evaluation of products containing nanomaterials. These biodistribution studies will, in effect, be indicative of where the nanoparticles are traveling and possibly accumulating, therefore subjecting those sites to increased likelihood of toxicological effects. This chapter focuses on questions and considerations that may arise for sponsors during product characterization, as well as considerations for the appropriate design and conduct of in vivo toxicology studies. This chapter will also review how current FDA guidances apply to nanotherapeutics.This chapter reflects the current thinking and experience of the authors. However, this is not a policy document and should not be used in lieu of regulations, published FDA guidances, or direct discussions with the agency.
美国食品药品监督管理局（FDA）尚未针对含有纳米级材料的产品制定具体指南。然而，正如FDA纳米技术特别工作组2007年7月发布的报告中所宣布的那样，已向FDA内部的各个中心提出了为行业制定指南的建议。尽管缺乏FDA的明确指南，但目前市场上已有含纳米级材料的治疗药物，并且正在研发更多含新型纳米材料的治疗药物，有望提交监管审查和批准。虽然在很大程度上，这些含新型纳米材料的产品是按照与不含纳米材料的产品相同的监管要求进行评估的，但越来越明显的是，至少在药品中使用的纳米材料表征领域，可能存在需要特别关注的方面。具体领域包括将小分子原理和方法应用于含纳米材料产品的有效性、纳米材料对制剂其他部分的影响（反之亦然），以及生物环境如何影响其物理化学性质。同样，对于安全性评估，生物分布研究将是任何含纳米材料产品评估的核心。这些生物分布研究实际上将表明纳米颗粒的移动和可能聚集的位置，从而使这些部位产生毒理学效应的可能性增加。本章重点关注申办者在产品表征过程中可能出现的问题和考虑因素，以及体内毒理学研究的适当设计和实施的考虑因素。本章还将回顾当前FDA指南如何适用于纳米治疗药物。本章反映了作者目前的想法和经验。然而，这不是一份政策文件，不应替代法规、已发布的FDA指南或与该机构的直接讨论。
