FDA發出警告: Genetech臍帶血產品 (ReGen5, ReGen10 and ReGen30)

12人注射幹細胞入院 FDA介入 盛益清 編譯報道 2019年01月04日美國食品藥品監督管理局（Food and Drug Administration，FDA）近日發佈公告：12 名患者在接受含有臍帶血幹細胞注射後，病情加重住院。目前，FDA 已向生產臍帶血產品的加州公司 Genetech涉事公司發出警告。並聲明，已書面通知了20 家提供未獲批幹細胞治療的診所，警告FDA會對其產品進行監管。所謂的幹細胞治療，即利用幹細胞具有自我更新、高度增殖、多向分化潛能的特性，在一定的條件下，讓這些「幹細胞」進一步分化成各種不同的組織細胞，參與細胞替代和組織再生。技術人員可以應用人自體或異體來源的幹細胞經體外分離、純化、培養、修飾、誘導分化等過程後回輸（或植入）人體，用於疾病預防和治療。然而，目前尚缺乏充份的科學證據證明幹細胞治療的安全和有效性。美國Centers for Disease Control and Prevention（CDC）的研究人員在網上發佈一份報告指，這些患者接受了膝蓋、肩膀或脊柱的注射，以治療關節炎或損傷等疼痛症狀。他們的血液或關節感染，所有人都已入院。最短的住院4天;其餘患者則住院12天、15天或35天。一人膝蓋感染，住院30天，另一名患者因血液感染、脊髓膿腫和其它脊柱問題在醫院度過了58天。提取診所注射的未打開的小瓶裝臍帶血產品進行檢測，發現患者感染的微生物種類相同，包括大腸桿菌和其它糞便細菌。FDA專員Scott Gottlieb博士表示，今年將會深入調查更多的幹細胞營運商，主要針對那些沒有遵守法律與FDA合作，並且可能從事不安全操作的機構。FDA表示已寫信給20家提供未經批准的幹細胞治療的診所，提醒它們這類產品通常是由FDA監管，並鼓勵這些診所在2020年11月之前聯繫美國聯邦監管機構，屆時將會收緊執法。 去年5月，FDA申請對兩家幹細胞診所實施永久性禁令。一家是美國佛羅里達州L.L.C. of Sunrise幹細胞診所，3名患者在幹細胞注射入眼睛後失明。另一家California Stem Cell Treatment Center位於Rancho Mirage and Beverly Hills，一直在為癌症患者提供天花疫苗和幹細胞的聯合治療。

FDA Warns Genetech for Unapproved Stem Cell Products Dec 26, 2018 By Pharmaceutical Technology Editors Editor's note: An earlier posting of this article incorrectly identified Genetech, Inc. as a subsidiary of Roche. The companies are not affiliated. We apologize for the error.  On Dec. 20, 2018, FDA announced that it sent a warning letter to Genetech, a San Diego, CA-based biotechnology company, about umbilical cord blood-derived cellular products distributed by Liveyon, a distributer of umbilical cord-derived products to physicians for use in regenerative medicine therapies. FDA is also sending letters to other firms and providers offering stem cell treatments notifying them of agency's regenerative medicine policy framework.  The letter addresses Genetech and its president, Edwin N. Pinos, for marketing stem cell products without FDA approval and for significant deviations from current good tissue practice (CGTP) and current good manufacturing practice (CGMP) requirements, including some violations that may have led to microbial contamination, potentially causing serious blood infections in patients. Genetech processed umbilical cord blood into unapproved human cellular products, which was distributed by Liveyon. FDA inspected Genetech's facility in June 2018 and found the company was processing cellular products from human umbilical cord blood for administration by intra-articular (joint) injection, intravenous injection, or application directly to the affected tissue to treat a variety of orthopedic conditions. These products were distributed by Liveyon in Yorba Linda, CA as ReGen5, ReGen10 and ReGen30. The Genetech products are not intended for homologous use (products that are intended for the same function in the recipient as the donor), and while the products have a systemic effect, they are not intended for allogeneic (genetically similar) use in a first or second-degree blood relative. As such, the products are regulated as both drug and biological products. To lawfully market these products, an approved biologics license application is needed. While in the development stage, the products may be used in humans only if an investigational new drug application is in effect. However, no such licenses or investigational new drug applications exist for the Genetech-processed, Liveyon-distributed products. During the inspection, the agency documented evidence of significant deviations from CGTP and CGMP requirements in the manufacture of the umbilical cord blood-derived products, including deficient donor eligibility practices, unvalidated manufacturing processes, uncontrolled environment, lack of control over the components used in production, and a lack of defined areas or a control system to prevent contamination and mix-ups. FDA reports that these deviations pose a significant risk that the products may be contaminated with microorganisms or have other serious product quality defects. FDA and the Centers for Disease Control and Prevention have received numerous reports of safety issues, including those involving microbial contamination and are aware of 12 patients who received Genetech products from Liveyon and subsequently became ill due to blood and other infections caused by a number of bacteria, including Escherichia coli (E. coli), as described in a forthcoming Morbidity and Mortality Weekly Report (MMWR), titled "Notes from the Field: Bloodstream and Joint Infections in Patients After Receiving Bacterially Contaminated Umbilical Cord Blood-derived Stem Cell Products for Non-hematopoietic Conditions—United States, 2018." In September 2018, Liveyon suspended shipment of all product pending an inquiry by FDA into the source of the adverse reactions. Liveyon also voluntarily recalled all Genetech products it may have distributed. FDA requested a response from Genetech, within 15 working days of the letter's issuance, that details how the deviations noted in the warning letter will be corrected. Deviations not corrected by companies and owners could lead to enforcement action such as seizure, injunction, or prosecution. Additionally, as part of FDA's overall goal to support the responsible development of safe and effective products for patients, the agency is sending letters to reiterate FDA's compliance and enforcement policy to other manufacturers and health care providers who may be offering stem cell treatments. "We remain committed to supporting the development of safe and effective cell-based regenerative medicine and advancing our comprehensive regenerative medicine policy framework," said FDA Commissioner Scott Gottlieb, MD, in an agency press release. "These efforts include our work to encourage manufacturers to engage with the FDA early so that we can provide guidance about any applicable regulatory requirements. Even though a few sponsors have come to us, we are discouraged by the overall lack of manufacturers wanting to interact with the agency in this enforcement discretion period. The letters we're issuing today to manufacturers, health care providers and clinics around the country are a reminder that there's a clear line between appropriate development of these products and practices that sidestep important regulatory controls needed to protect patients. Time is running out for firms to come into compliance during our period of enforcement discretion. We'll be increasing our oversight related to cell-based regenerative medicine as part of our comprehensive plan to promote beneficial innovation while protecting patients." Health care professionals and consumers should report any adverse events related to treatments with the Liveyon products, Genetech products, or other stem cell treatments.  Source: FDA