Accelerating Drug Product Development and Approval: Early Development and Evaluation
Accelerating Drug Product Development and Approval: Early Development and Evaluation
复制标题
加速药品开发和审批：早期开发和评估
DOI：
10.1007/s11095-023-03566-1
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发表时间：
2024
影响因子：
3.7
通讯作者：
Templeton, Allen
中科院分区：
文献类型：
--
作者：
Bak, Annette;Burlage, Rubi;Greene, Nigel;Nambiar, Prabu;Lu, Xiuling;Templeton, Allen
一个重大的发现和早期开发挑战一直是并且仍然是如何尽快为患者开发最好和最有影响力的药物，这两个目标从表面上看可能是矛盾的。近年来尤其如此，治疗方式已显着扩展，不仅包括传统的小分子和蛋白质，还包括肽、抗体药物偶联物 (ADC)、各种基于核苷酸的疗法，例如反义寡核苷酸 (ASO)、小干扰核糖核酸 (siRNA)、信使 RNA (mRNA) 以及细胞和基因疗法 [1-3]，仅举几例。有关 CDER 批准的 BLA（生物制剂许可申请）和 NME（新分子实体）申请的概述，请参见图 1（源数据来自 [4]）。从图中可以看出，BLA的数量呈上升趋势，而传统NME的数量呈下降趋势。陈等人[5]我们更详细地研究了这些数据，因此可以看出，小分子申请的数量正在下降，而蛋白质治疗药物的数量正在增加。所有模式对临床前和药品开发都有自己的要求，这可能会导致复杂性和消耗[6]。2023年1月，国家制药技术与教育研究所（NIPTE）关于加速药品开发和审批的探路研讨会“早期开发和评估”会议重点关注四个方面的发展障碍：化学、制造和控制（CMC）、药物输送、使能技术和监管障碍；然后针对最关键的方面提供解决方案。表一总结了参与者确定的障碍。正如表中总结和面对面讨论中进一步概述的那样，由于新的科学、工艺和下游能力建设，药物输送和 CMC 障碍将减缓后期发现和早期开发。对于新疗法（ADC、RNA 和细胞/基因疗法）来说尤其如此，因为 CMC 周期与更成熟的疗法以及不同的分销渠道有很大不同 [7, 8]。当中枢神经系统（CNS）和细胞内靶标等难以进入的组织中的疾病需要定制的释放曲线和/或复杂的药物输送策略时，这也适用于制剂技术[9]。
A major discovery and early development challenge has been and still is how to develop the best and most impactful medicines for patients as fast as possible, two aims that can appear at face value to be contradicting. This is especially the case in recent times, where the modality landscape has expanded significantly to not only include traditional small molecules and proteins, but also peptides, antibody drug conjugates (ADC), a variety of nucleotide-based therapies such as antisense oligonucleotides (ASO), small interfering ribonucleic acids (siRNA), messenger RNAs (mRNA), and cell and gene therapies [1–3] just to name a few. See Fig. 1 (Source data from [4]) for an overview over BLA (Biologics License Application) and NME (New Molecular Entity) applications approved by CDER. From the figure it can be seen that the number of BLAs trends up, while the number of traditional NMEs trend down. Chen et al.[5] have looked at this data in further details and accordingly it can be seen that the number of small molecule filings are going down while the number of protein therapeutics are increasing. All modalities have their own requirements for preclinical and drug product development, which can lead to complexity and attrition [6].The January 2023 National Institute for Pharmaceutical Technology & Education (NIPTE) pathfinding workshop on accelerating drug product development and approval, the “Early Development and Evaluation” session was focused on development barriers within four aspects–chemistry, manufacturing and controls (CMC), drug delivery, enabling technologies and regulatory barriers; and then providing solutions to the most critical aspects. The barriers identified by participants are summarized in Table I. As summarized in the table and further outlined in the face-to-face discussions, drug delivery and CMC barriers will slow down late discovery and early development as a result of new science, processes, and downstream capability builds. This is especially true for the new modalities (ADCs, RNA and cell/gene therapies) due to CMC cycles that are very different from more established modalities along with different distribution channels [7, 8]. This also applies for formulation technologies when tailored release profiles and/or sophisticated drug delivery strategies are needed for diseases in hard to access tissues such as the Central Nervous System (CNS) and intracellular targets [9].