Miesle James E, Osei-Yeboah Frederick, Pauli-Bruns Anette, Chen Bei, Manceva Slobodanka, Wade Jonathan B, Yin Shawn, Desai Divyakant, Dirat Olivier, Bhugra Chandan, Stauffer Fanny
Synthetic Molecule Design and Development, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
Pharmaceutical Development, Biogen, Cambridge, MA, USA.
Pharm Res. 2024 Sep;41(9):1775-1786. doi: 10.1007/s11095-024-03765-4. Epub 2024 Sep 4.
The concept of a Design Space (DSp) was introduced in ICH Q8 as a tool within the quality-by-design (QbD) approach to pharmaceutical development with the intent of being globally applicable. However, there appears to be variance in the regulatory agency expectations in pharmaceutical product filing and implementation of DSp. This paper presents some of the current industry perspective on design space.
The Utilization of Design Space for Filings (UDSpF) Working Group in the Innovation and Quality (IQ) Consortium conducted a survey to establish a baseline for the current understanding of DSp among IQ member companies and assess the similarities and/or differences in strategies when filing a DSp. The survey focused on how IQ member companies approach DSp development, the primary drivers for the DSp, the presentation of the DSp in the filing, DSp verification and the benefits and flexibility anticipated and/or realized.
A total of 14 responses were received and analyzed representing a small sample size but a large proportion of the innovator industry/large pharmaceutical companies. The survey results revealed that DSp is not yet a commonplace for small molecule drug products and may not even be utilized as much in large molecule drug products. The benefits of DSp, with respect to enhanced process understanding, are well understood by the sponsors; however, the benefits of filed DSp with respect to manufacturing flexibility are not fully realized in the commercial lifecycle of the product. There are also challenges in gaining consistent buy-in/value proposition for DSp among cross-functional teams within organizations.
There are still gaps in design space implementation for its full benefit in the pharmaceutical industry. The WG has presented a unified view from member companies on the approach to DSp considering when/where the DSp experiments are conducted and on the extent of the DSp development proposed in a dossier.
设计空间（DSp）的概念在国际人用药品注册技术协调会（ICH）Q8中被引入，作为药物研发的质量源于设计（QbD）方法中的一种工具，旨在全球范围内适用。然而，监管机构对药品申报和DSp实施的期望似乎存在差异。本文介绍了当前行业对设计空间的一些观点。
创新与质量（IQ）协会的设计空间申报利用（UDSpF）工作组进行了一项调查，以建立IQ成员公司对DSp当前理解的基线，并评估申报DSp时策略的异同。该调查聚焦于IQ成员公司如何进行DSp开发、DSp的主要驱动因素、申报中DSp的呈现、DSp验证以及预期和/或实现的益处与灵活性。
共收到并分析了14份回复，样本量虽小，但代表了创新药行业/大型制药公司的很大一部分。调查结果显示，DSp在小分子药物产品中尚未普遍应用，在大分子药物产品中甚至可能也未得到充分利用。申办方充分理解DSp在增强工艺理解方面的益处；然而，申报的DSp在产品商业生命周期中关于生产灵活性的益处尚未完全实现。在组织内跨职能团队中，要使DSp获得一致的认可/价值主张也存在挑战。
在制药行业充分发挥设计空间的全部益处方面，其实施仍存在差距。工作组已就DSp的方法提出了成员公司的统一观点，考虑了DSp实验的时间/地点以及申报资料中提议的DSp开发程度。
