Nanoparticle Therapeutics: FDA Approval, Clinical Trials, Regulatory Pathways, and Case Study
Nanoparticle Therapeutics: FDA Approval, Clinical Trials, Regulatory Pathways, and Case Study
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DOI：
10.1007/978-1-61779-052-2_21
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发表时间：
2011-01-01
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影响因子：
--
通讯作者：
Thaxton, C. Shad
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文献类型：
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作者：
Eifler, Aaron C.;Thaxton, C. Shad
美国食品和药物管理局（FDA）通过药物评价和研究中心（CDER）批准人用药物是一个耗时且昂贵的过程，批准率较低（DiMasi et al.，J Health Econ 22：151-185，2003; Marchetti和Schellens，Br J Cancer 97：577-581，2007）。一般来说，FDA的药物批准过程可以分为临床前、临床和上市后阶段。在从发现到证明人体安全性和有效性的每一步中，候选药物都受到严格审查。纳米技术的进展正应用于新型治疗剂的开发，其可以解决常规小分子药物的许多缺点并且可以促进个性化药物的实现（Ferrari，Curr Opin Chem Biol 9：343-346，2005; Ferrari，Nat Rev Cancer 5：161-171，2005; Ferrari和Downing，BioDrugs 19：203-210，2005）。吸引人的是，纳米颗粒候选药物通常代表多重制剂（例如，药物、靶向部分和纳米颗粒支架材料）。通过定制可变纳米颗粒成分的化学和特性，可以实现靶向递送，减少副作用，并制备不稳定的（例如，siRNA）和/或高毒性药物（Ferrari，Curr Opin Chem Biol 9：343-346，2005; Ferrari，Nat Rev Cancer 5：161-171，2005; Ferrari和Downing，BioDrugs 19：203-210，2005）。随着这些好处出现在监管药物开发和测试的各个方面的新挑战。本章提炼了药物开发和批准过程，重点是纳米治疗的特殊考虑。本章以一个案例研究结束，该案例研究集中在纳米颗粒治疗剂CALAA-01上，该纳米颗粒治疗剂目前处于人体临床试验中，体现了纳米颗粒治疗剂的许多潜在益处（Davis，Mol Pharm 6：659-668，2009）。通过选择CALAA-01，参考了治疗性纳米颗粒领域的婴儿期; 2008年，CALAA-01是第一个给予人类的靶向siRNA纳米颗粒治疗剂。当然，还会有更多的药物遵循CALAA-01的领导，每种药物都有自己独特的挑战;但是，在纳米治疗的背景下，可以从这种药物中学到很多东西，以及适用于它们的不断发展的开发和批准过程。
The approval of drugs for human use by the US Food and Drug Administration (FDA) through the Center for Drug Evaluation and Research (CDER) is a time-consuming and expensive process, and approval rates are low (DiMasi et al., J Health Econ 22:151-185, 2003; Marchetti and Schellens, Br J Cancer 97:577-581, 2007). In general, the FDA drug approval process can be separated into preclinical, clinical, and postmarketing phases. At each step from the point of discovery through demonstration of safety and efficacy in humans, drug candidates arc closely scrutinized. Advances in nanotechnology are being applied in the development of novel therapeutics that may address a number of shortcomings of conventional small molecule drugs and may facilitate the realization of personalized medicine (Ferrari, Curr Opin Chem Biol 9:343-346, 2005; Ferrari, Nat Rev Cancer 5:161-171, 2005; Ferrari and Downing, BioDrugs 19:203-210, 2005). Appealingly, nanoparticle drug candidates often represent multiplexed formulations (e.g., drug, targeting moiety, and nanoparticle scaffold material). By tailoring the chemistry and identity of variable nanoparticle constituents, it is possible to achieve targeted delivery, reduce side effects, and prepare formulations of unstable (e.g., siRNA) and/or highly toxic drugs (Ferrari, Curr Opin Chem Biol 9:343-346, 2005; Ferrari, Nat Rev Cancer 5:161-171, 2005; Ferrari and Downing, BioDrugs 19:203-210, 2005). With these benefits arise new challenges in all aspects of regulated drug development and testing.This chapter distils the drug development and approval process with an emphasis on special considerations for nanotherapeutics. The chapter concludes with a case study focused on a nanoparticle therapeutic, CALAA-01, currently in human clinical trials, that embodies many of the potential benefits of nanoparticle therapeutics (Davis, Mol Pharm 6:659-668, 2009). By choosing CALAA-01, reference is made to the infancy of the therapeutic nanoparticle field; in 2008, CALAA-01 was the first targeted siRNA nanoparticle therapeutic administered to humans. Certainly, there will be many more that will follow the lead of CALAA-01 and each will have its own unique challenges; however, much can be learned from this drug in the context of nanotherapeutics and the evolving development and approval process as it applies to them.