Park Jin-Young K, Lee Daniel, Rui Lixin, Gao Xiaoyue, Furness M Scott, Wu Charles
Office of Pre-Market Additive Safety, Office of Food Chemical Safety, Dietary Supplements, and Innovation, Human Foods Program, Food and Drug Administration, College Park, MD, 20740, USA.
Office of Oncologic Disease, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, 20993, USA.
Ther Innov Regul Sci. 2025 Jun 4. doi: 10.1007/s43441-025-00786-y.
The United States Food and Drug Administration (FDA) has received over 700 botanical investigational new drug applications (INDs) in a broad spectrum of therapeutic areas since 1984. The greatest numbers were for cancer management. The aims of our study were to conduct a first-time, in-depth analysis of the regulatory submission profiles for botanical INDs with oncologic indications, in comparison with non-oncologic indications, and to share our regulatory review experience of oncologic botanical drug research and development.
The FDA Center for Drug Evaluation and Research (CDER) maintains an in-house database of botanical INDs that contains many data elements, including initial 30-day actions (safe-to-proceed, clinical hold, etc.), current regulatory status, primary purpose of the proposed clinical trials, and initially proposed clinical trial phase information by sponsor. The database provided internally validated regulatory submission information that FDA received between March 1984 and December 2020 for 254 botanical INDs with oncologic indications, as well as 485 non-oncologic botanical INDs.
A higher percentage of the oncologic botanical INDs (69% versus 58% for non-oncologic botanical INDs, p < 0.01) received an initial 30-day safe-to-proceed designation to initiate the clinical investigations. One hundred thirty-seven oncologic botanical INDs were submitted to conduct phase 1 trials to investigate the safety and tolerability of their products, and 46 of these INDs are currently active. An additional 117 INDs were proposed to conduct phase 2 or phase 3 trials to assess safety and efficacy of oncologic botanical products, and 36 of those INDs are currently active, including 3 INDs in phase 3 trials. Most of the oncologic botanical INDs were for the investigation of specific solid tumors (71%) with more than one third of these related to prostate and breast tumors.
Despite the scientific and regulatory challenges that FDA reviewers previously experienced, our analysis shows that there were over 80 currently active botanical oncologic INDs, including several in the late phase of drug development for cancer management. The implication of this finding is significant in that many clinical trials of botanical drug products intended to provide high-quality cancer patient care are in the regulatory pipeline.
自1984年以来，美国食品药品监督管理局（FDA）已收到700多份植物性研究性新药申请（IND），涉及广泛的治疗领域。其中数量最多的是癌症治疗领域。我们研究的目的是首次对有肿瘤适应症的植物性IND与非肿瘤适应症的植物性IND的监管申报概况进行深入分析，并分享我们对肿瘤植物药研发的监管审查经验。
FDA药品评价和研究中心（CDER）维护一个植物性IND的内部数据库，其中包含许多数据元素，包括最初的30天行动（可继续进行、临床搁置等）、当前监管状态、拟进行临床试验的主要目的以及申办方最初提议的临床试验阶段信息。该数据库提供了FDA在1984年3月至2020年12月期间收到的254份有肿瘤适应症的植物性IND以及485份非肿瘤植物性IND的内部验证监管申报信息。
有更高比例的肿瘤植物性IND（69%，而非肿瘤植物性IND为58%，p<0.01）获得了最初30天可继续进行的指定以启动临床研究。137份肿瘤植物性IND被提交以进行1期试验来研究其产品的安全性和耐受性，其中46份IND目前仍在进行中。另外117份IND被提议进行2期或3期试验以评估肿瘤植物产品的安全性和有效性，其中36份IND目前仍在进行中，包括3份处于3期试验的IND。大多数肿瘤植物性IND是用于特定实体瘤的研究（71%），其中超过三分之一与前列腺和乳腺肿瘤相关。
尽管FDA审评员此前经历了科学和监管方面的挑战，但我们的分析表明，目前有超过80份活跃的肿瘤植物性IND，包括几份处于癌症治疗药物开发后期的IND。这一发现的意义重大，因为许多旨在为癌症患者提供高质量护理的植物药产品的临床试验正在监管流程中。
