Division of Pharmacoepidemiology and Clinical Pharmacology of the Utrecht Institute for Pharmaceutical Sciences (UIPS); Dutch Medicines Evaluation Board, Utrecht, The Netherlands.
Division of Pharmacoepidemiology and Clinical Pharmacology of the Utrecht Institute for Pharmaceutical Sciences (UIPS).
Cytotherapy. 2020 Jul;22(7):388-397. doi: 10.1016/j.jcyt.2020.03.432. Epub 2020 May 12.
Recent technical and clinical advances with cell-based therapies (CBTs) hold great promise in the treatment of patients with rare diseases and those with high unmet medical need. Currently the majority of CBTs are developed and manufactured in specialized academic facilities. Due to small scale, unique characteristics and specific supply chain, CBT manufacturing is considered costly compared to more conventional medicinal products. As a result, biomedical researchers and clinicians are increasingly faced with cost considerations in CBT development. The objective of this research was to develop a costing framework and methodology for academic and other small-scale facilities that manufacture cell-based therapies.
We conducted an international multi-center costing study in four facilities in Europe using eight CBTs as case studies. This study includes costs from cell or tissue procurement to release of final product for clinical use. First, via interviews with research scientists, clinicians, biomedical scientists, pharmacists and technicians, we designed a high-level costing framework. Next, we developed a more detailed uniform methodology to allocate cost items. Costs were divided into steps (tissue procurement, manufacturing and fill-finish). The steps were each subdivided into cost categories (materials, equipment, personnel and facility), and each category was broken down into facility running (fixed) costs and operational (variable) costs. The methodology was tested via the case studies and validated in developer interviews. Costs are expressed in 2018 euros (€).
The framework and methodology were applicable across facilities and proved sensitive to differences in product and facility characteristics. Case study cost estimates ranged between €23 033 and €190 799 Euros per batch, with batch yield varying between 1 and 88 doses. The cost estimations revealed hidden costs to developers and provided insights into cost drivers to help design manufacturing best practices.
This framework and methodology provide step-by-step guidance to estimate manufacturing costs specifically for cell-based therapies manufactured in academic and other small-scale enterprises. The framework and methodology can be used to inform and plan cost-conscious strategies for CBTs.
细胞疗法（CBT）的最新技术和临床进展为治疗罕见病患者和高未满足医疗需求的患者带来了巨大希望。目前，大多数 CBT 都是在专门的学术机构中开发和制造的。由于规模较小、独特的特点和特定的供应链，与更传统的药物产品相比，CBT 制造被认为成本更高。因此，生物医学研究人员和临床医生在 CBT 开发中越来越面临成本考虑。本研究的目的是为制造细胞疗法的学术和其他小型设施开发成本核算框架和方法。
我们在欧洲的四个设施中进行了一项国际多中心成本研究，使用 8 种 CBT 作为案例研究。本研究包括从细胞或组织采购到最终产品放行用于临床使用的成本。首先，通过对研究科学家、临床医生、生物医学科学家、药剂师和技术人员进行访谈，我们设计了一个高级别的成本核算框架。接下来，我们开发了一种更详细的统一方法来分配成本项目。成本分为步骤（组织采购、制造和灌装完成）。每个步骤进一步细分为成本类别（材料、设备、人员和设施），每个类别进一步细分为设施运行（固定）成本和运营（可变）成本。该方法通过案例研究进行了测试，并通过开发者访谈进行了验证。成本以 2018 年欧元（€）表示。
该框架和方法适用于不同的设施，并证明对产品和设施特点的差异具有敏感性。案例研究的成本估算范围为每个批次 23,033 至 190,799 欧元，每个批次的产量在 1 至 88 剂之间。成本估算揭示了开发者的隐藏成本，并深入了解了成本驱动因素，以帮助设计制造最佳实践。
该框架和方法为在学术和其他小型企业中制造的细胞疗法的制造成本提供了逐步指导。该框架和方法可用于为 CBT 提供成本意识策略的信息和规划。
