End-to-end donor screening and manufacturing controls: complementary quality-based strategies to minimize patient risk for donor-derived microbiome therapeutics.

IF 12.2 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Gut Microbes Pub Date : 2024-09-18 DOI:10.1080/19490976.2024.2402550

Jason Goldsmith,Sarah Tomkovich,John G Auniņš,Barbara H McGovern,Jennifer C Mahoney,Brooke R Hasson,Christopher W J McChalicher,David S Ege

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引用次数: 0

Abstract

Advances in microbiome therapeutics have been motivated by a deeper understanding of the role that the gastrointestinal microbiome plays in human health and disease. The FDA approval of two stool-derived live biotherapeutic products (LBPs), REBYOTA® 150 mL enema (fecal microbiota, live-jslm; formerly RBX2660) and VOWST® oral capsules (fecal microbiota spores, live-brpk; formerly SER-109), for the prevention of recurrent CDI in adults following antibiotic treatment for recurrent CDI provides promise and insights for the development of LBPs for other diseases associated with microbiome dysfunction. Donor-derived products carry risk of disease transmission that must be mitigated through a robust donor screening program and downstream manufacturing controls. Most published recommendations for donor screening practices are prescriptive and do not include a systematic, risk-based approach for donor stool-derived products. A general framework for an end-to-end donor screening program is needed using risk management strategies for donor-derived microbiome therapeutic using a matrixed approach, combining the elements of donor screening with manufacturing controls that are designed to minimize risk to patients. A donor screening paradigm that incorporates medical history, physical examination, laboratory testing, and donor sample inspection are only the first steps in reducing risk of transmission of infectious agents. Manufacturing controls are the cornerstone of risk mitigation when screening unwittingly fails. Failure Mode and Effects Analysis (FMEA) can be used as a tool to assess for residual risk that requires further donor or manufacturing controls. Together, a well-reasoned donor program and manufacturing controls are complementary strategies that must be revisited and reexamined frequently with constant vigilance to mitigate risk to patients. In the spirit of full disclosure and informed consent, physicians should discuss any limitations in the donor screening and manufacturing processes with their patients prior to treatment with microbiome-based therapeutics.

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端到端供体筛选和生产控制：基于质量的互补策略，最大限度地降低供体微生物组疗法的患者风险。

对胃肠道微生物组在人类健康和疾病中所起作用的深入了解推动了微生物组疗法的发展。美国食品及药物管理局（FDA）批准了两种粪便来源的活生物治疗产品（LBPs），即 REBYOTA® 150 mL 灌肠剂（粪便微生物群，活-jslm；前身为 RBX2660）和 VOWST® 口服胶囊（粪便微生物群孢子，活-brpk；前身为 SER-109），用于预防成人在接受抗生素治疗后复发的 CDI，这为开发治疗其他与微生物群功能障碍相关疾病的 LBPs 提供了希望和启示。供体衍生产品存在疾病传播风险，必须通过健全的供体筛选计划和下游生产控制措施来降低风险。大多数已发布的供体筛查实践建议都是指令性的，并不包括针对供体粪便衍生产品的系统性、基于风险的方法。我们需要一个端到端供体筛选计划的总体框架，采用矩阵式方法对供体衍生的微生物组疗法进行风险管理策略，将供体筛选要素与旨在最大限度降低患者风险的生产控制相结合。包括病史、体格检查、实验室检测和供体样本检查在内的供体筛选模式只是降低传染源传播风险的第一步。当筛查无意中失败时，生产控制是降低风险的基石。失效模式及影响分析 (FMEA) 可用作评估残余风险的工具，需要对供体或生产进行进一步控制。合理的供体计划和生产控制是相辅相成的策略，必须经常重新审视和检查，时刻保持警惕，以降低患者面临的风险。本着充分披露和知情同意的精神，医生应在使用基于微生物组的疗法治疗前与患者讨论供体筛选和生产过程中的任何限制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gut Microbes Medicine-Microbiology (medical)

CiteScore

18.20

自引率

3.30%

发文量

196

审稿时长

10 weeks

期刊介绍： The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more. Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.