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确定在医院豁免情况下放行自体新鲜嵌合抗原受体T细胞产品所需的条件和最低要求:UNITC联盟WP生物生产部门的立场文件

Identification of the conditions and minimum requirements necessary for the release of autologous fresh CAR T-cell products under hospital exemption: a position paper from the WP-bioproduction of the UNITC consortium.

作者信息

Boyer Olivier, Bensoussan Daniele, Bönig Halvard, Chabannon Christian, Clémenceau Béatrice, Cuffel Alexis, Dachy Guillaume, de Vos John, Derenne Sophie, Diana Jean-Sébastien, Dougé Aurore, Deramoudt Laure, Ferrand Christophe, Forcade Edouard, Galaine Jeanne, Galy Anne, Giverne Camille, Martinet Jérémie, Marton Chrystel, Larghero Jérôme, Reppel Loïc, Viel Sébastien, Yakoub-Agha Ibrahim, Deschamps Marina

机构信息

Univ Rouen Normandie, Inserm, UMR 1234, CHU de Rouen, Department of Immunology and Biotherapy, F-76000, Rouen, France.

CHRU de Nancy, Unité de Thérapie cellulaire et Banque de Tissus (UTCT). Université de Lorraine, UMR 7365 IMoPA, Vandoeuvre-les-Nancy, France.

出版信息

Bone Marrow Transplant. 2025 Apr;60(4):431-438. doi: 10.1038/s41409-024-02504-y. Epub 2025 Jan 25.


DOI:10.1038/s41409-024-02504-y
PMID:39863732
Abstract

The accessibility of CAR-T cells in centralized production models faces significant challenges, primarily stemming from logistical complexities and prohibitive costs. However, European Regulation EC No. 1394/2007 introduced a pivotal provision known as the hospital exemption. This exemption enables academic institutions to produce ATMPs, including autologous CAR-T cells, under GMP conditions tailored to specific needs. In response to this regulatory framework, our work group has launched a guideline initiative. This endeavor aims to bolster academic CAR T-cell manufacturing by implementing strategic workshops that serve a dual purpose: standardizing production processes and ensuring both efficacy and safety standards are met. This inaugural focused on delineating criteria for the release of fresh CAR-T cell batches. Key emphases included thorough product characterization, stringent safety and potency evaluations. These criteria are essential for compliance with regulatory mandates and aligning with industry best practices. Notably, the release of initial CAR T-cell batches will be facilitated through provisional certification, with final certification contingent upon the acquisition of comprehensive analytical control results. This procedural framework adheres to methodologies endorsed by the SFGM-TC and the EBMT. Such adherence underscores a commitment to harmonizing practices across academic manufacturing facilities, thus fortifying the accessibility, efficacy, and safety of point-of-care units.

摘要

在集中生产模式下,嵌合抗原受体T细胞(CAR-T细胞)的可及性面临重大挑战,主要源于后勤复杂性和高昂成本。然而,欧盟第1394/2007号法规引入了一项关键条款,即医院豁免。这项豁免使学术机构能够在根据特定需求定制的药品生产质量管理规范(GMP)条件下生产先进治疗药品(ATMP),包括自体CAR-T细胞。针对这一监管框架,我们的工作小组发起了一项指南倡议。这项工作旨在通过开展具有双重目的的战略研讨会来加强学术性CAR-T细胞制造:使生产流程标准化,并确保满足疗效和安全标准。本次首次研讨会着重于界定新鲜CAR-T细胞批次放行的标准。重点包括全面的产品特性鉴定、严格的安全性和效力评估。这些标准对于符合监管要求以及与行业最佳实践保持一致至关重要。值得注意的是,初始CAR-T细胞批次的放行将通过临时认证来促进,最终认证取决于获得全面的分析控制结果。这一程序框架遵循了法国药品安全局治疗产品科学技术委员会(SFGM-TC)和欧洲血液与骨髓移植协会(EBMT)认可的方法。这种遵循强调了致力于协调学术制造机构之间的做法,从而增强床边医疗单元的可及性、疗效和安全性。

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引用本文的文献

[1]
Harmonisation of quality control tests for academic production of CAR-T cells: a position paper from the WP-bioproduction of the UNITC consortium.

Bone Marrow Transplant. 2025-5-29

本文引用的文献

[1]
Long-term stability of clinical-grade lentiviral vectors for cell therapy.

Mol Ther Methods Clin Dev. 2024-1-10

[2]
CAR-T cell manufacturing: Major process parameters and next-generation strategies.

J Exp Med. 2024-2-5

[3]
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Bull Cancer. 2024-1

[4]
Automated production of gene-modified chimeric antigen receptor T cells using the Cocoon Platform.

Cytotherapy. 2023-12

[5]
Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study.

Lancet Oncol. 2023-8

[6]
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Cancers (Basel). 2023-2-4

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Rapid Sterility Test Systems in the Pharmaceutical Industry: Applying a Structured Approach to Their Evaluation, Validation and Global Implementation.

PDA J Pharm Sci Technol. 2023

[8]
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Methods Cell Biol. 2023

[9]
Results of ARI-0001 CART19 cell therapy in patients with relapsed/refractory CD19-positive acute lymphoblastic leukemia with isolated extramedullary disease.

Am J Hematol. 2022-6-1

[10]
Lentiviral standards to determine the sensitivity of assays that quantify lentiviral vector copy numbers and genomic insertion sites in cells.

Gene Ther. 2022-9

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