Product Development, Quality, and Supply (PDQS), Seres Therapeutics, Inc., Cambridge, MA, USA.
Gut Microbes. 2024 Jan-Dec;16(1):2402550. doi: 10.1080/19490976.2024.2402550. Epub 2024 Sep 18.
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.
微生物组治疗学的进展源于对胃肠道微生物组在人类健康和疾病中所起作用的更深入理解。FDA 批准了两种源自粪便的活体生物治疗产品（LBPs），REBYOTA®150mL 灌肠剂（粪便微生物组，活体-jslm；前身为 RBX2660）和 VOWST®口服胶囊（粪便微生物组孢子，活体-brpk；前身为 SER-109），用于预防成人在因复发性 CDI 而接受抗生素治疗后再次发生 CDI，这为开发与微生物组功能障碍相关的其他疾病的 LBPs 提供了希望和思路。供体来源的产品存在疾病传播的风险，必须通过严格的供体筛选计划和下游生产控制来减轻。大多数已发表的供体筛选实践建议都是规定性的，不包括针对供体粪便衍生产品的系统、基于风险的方法。需要使用基于风险管理的策略来建立一个端到端的供体筛选计划框架，该策略使用矩阵方法来对供体衍生的微生物组治疗进行分类，将供体筛选的要素与旨在最大限度降低患者风险的生产控制相结合。纳入病史、体格检查、实验室检测和供体样本检查的供体筛选模式只是降低传染性病原体传播风险的第一步。生产控制是筛选失败时减轻风险的基石。失效模式与影响分析（FMEA）可用于评估需要进一步进行供体或生产控制的剩余风险。一个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重新检查，以保持对患者风险的警惕。本着充分披露和知情同意的精神，医生在使用基于微生物组的治疗方法治疗患者之前，应与患者讨论供体筛选和生产过程中的任何限制。
