FDA guides on Covid-19 con sid er a tions in cell and gene ther a py

FDA关于Covid-19在细胞和基因治疗中的应用指南

2021-01-22 07:00:22 ENDPOINTS NEWS

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Man­u­fac­tur­ers of cell and gene ther­a­pies have a new guid­ance from the FDA that pro­vides pan­dem­ic-re­lat­ed man­u­fac­tur­ing con­sid­er­a­tions. The guid­ance specif­i­cal­ly ad­dress­es both li­censed and in­ves­ti­ga­tion­al cell and gene ther­a­py (CGT) man­u­fac­ture, and “is in­tend­ed to sup­ple­ment the rec­om­men­da­tions to drug and bi­o­log­i­cal prod­uct man­u­fac­tur­ers pro­vid­ed in FDA’s ‘Good Man­u­fac­tur­ing Prac­tice Con­sid­er­a­tions for Re­spond­ing to COVID-19 In­fec­tion in Em­ploy­ees in Drug and Bi­o­log­i­cal Prod­ucts Man­u­fac­tur­ing; Guid­ance for In­dus­try’ is­sued in June 2020,” ac­cord­ing to the guid­ance. In­dus­try-spe­cif­ic is­sues ad­dressed in the guid­ance in­clude cells and tis­sues re­cov­ered from donors and the par­tic­u­lar meth­ods by which a CGT prod­uct will be man­u­fac­tured, such as cell ex­pan­sion, vi­ral re­duc­tion steps, and for­mu­la­tion. The guid­ance ap­plies to CGT prod­ucts reg­u­lat­ed as drugs and bi­o­log­ic prod­ucts alike, but not to de­vices or hu­man cells, tis­sues, and cel­lu­lar- or tis­sue-based prod­ucts (HCT/Ps) reg­u­lat­ed un­der sec­tion 361 of the PHS Act. There has been no known con­t­a­m­i­na­tion of HCT/Ps with SARS-CoV-2, the virus that caus­es COVID-19, not­ed the agency. Fur­ther, res­pi­ra­to­ry virus­es are not gen­er­al­ly con­sid­ered to be trans­mit­ted through use of HCT/Ps. “How­ev­er, as not­ed in FDA’s June 2020 GMP Guid­ance, (Ref. 1), SARS-CoV-2 is a nov­el coro­n­avirus and, to en­sure com­pli­ance with cur­rent good man­u­fac­tur­ing prac­tice (CGMP) re­quire­ments, CGT man­u­fac­tur­ers are ex­pect­ed to eval­u­ate whether it pos­es new risks in the con­text of their spe­cif­ic prod­ucts, fa­cil­i­ties, process­es, and man­u­fac­tur­ing con­trols.” A key con­sid­er­a­tion for risk as­sess­ment is the po­ten­tial for ac­ci­den­tal ex­pan­sion of SARS-CoV-2 virus dur­ing cell cul­ture of au­tol­o­gous or al­lo­gene­ic cells, if they were in­fect­ed with the virus. This, wrote FDA, could re­sult in “a fi­nal prod­uct with am­pli­fied SAR-CoV-2 vi­ral load.” Al­lo­gene­ic prod­ucts, es­pe­cial­ly those com­ing from cell banks, may car­ry high­er risk than au­tol­o­gous prod­ucts, for ex­am­ple. FDA ad­vis­es con­tin­u­a­tion of rou­tine screen­ing mea­sures for donor as­sess­ment. The con­sid­er­a­tions FDA puts for­ward are based on “lim­it­ed in­for­ma­tion,” but in­clude whether an al­lo­gene­ic or au­tol­o­gous donor has, in the 28 days pre­ced­ing cell or tis­sue re­cov­ery, been in close con­tact with a Covid-19-in­fect­ed in­di­vid­ual, or been di­ag­nosed with or had a pos­i­tive test for Covid-19. FDA con­tin­ues to rec­om­mend against screen­ing asymp­to­matic donors for SAR-CoV-2. How­ev­er, an au­tho­rized, cleared, or ap­proved test may be used as part of a risk mit­i­ga­tion strat­e­gy in CGT prod­uct man­u­fac­ture. “At this time, FDA rec­om­mends that es­tab­lish­ments not screen for or de­fer HCT/P donors who have been vac­ci­nat­ed against COVID-19 with non-repli­cat­ing, in­ac­ti­vat­ed, or RNA-based COVID-19 vac­cines,” added the agency in the guid­ance. In terms of cel­lu­lar and tis­sue source ma­te­r­i­al, FDA should con­sid­er what is known about coro­n­avirus­es in gen­er­al and SARS-CoV-2 in par­tic­u­lar, in­clud­ing its propen­si­ty to prop­a­gate in par­tic­u­lar tis­sues. This is an evolv­ing area, and man­u­fac­tur­ers should cite the sci­en­tif­ic lit­er­a­ture and pro­vide jus­ti­fi­ca­tion for risk as­sess­ment and mit­i­ga­tion. Man­u­fac­tur­ing con­sid­er­a­tions in­clude re­duc­ing con­t­a­m­i­na­tion risk through good em­ploy­ee san­i­ta­tion and health prac­tices. The guid­ance points out that SARS-CoV-2 “has been shown to be ca­pa­ble of in­fect­ing and repli­cat­ing in cells com­mon­ly used for vec­tor pro­duc­tion (e.g., HEK293 and Vero cells),” a fact that man­u­fac­tur­ers should weigh in risk as­sess­ment and in for­mu­lat­ing mit­i­ga­tion strate­gies. No par­tic­u­lar ma­te­r­i­al test­ing rec­om­men­da­tions are in the guid­ance, but FDA does rec­om­mend ful­ly meet­ing CGMP re­quire­ments in­clud­ing ap­proval of all eval­u­a­tions by the man­u­fac­tur­er’s qual­i­ty unit and doc­u­men­ta­tion in the qual­i­ty man­age­ment sys­tem. FDA has made the guid­ance im­me­di­ate­ly ef­fec­tive dur­ing the pub­lic health emer­gency of the Covid-19 pan­dem­ic, but the agency is still ac­cept­ing pub­lic com­ments on the guid­ance at any point. So­cial im­age cred­it: Get­ty Im­ages RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion. By RBC Capital Markets With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures Key Points Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities. Unlocking the potential of the microbiome could be the missing link to better disease diagnosis. Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies. Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom. GlaxoSmithKline’s HIV unit ViiV was dealt a stinging loss back in late 2019 when the FDA slammed the brakes on its application for a once-monthly injection based on manufacturing issues. Now, with that roadblock in the rearview, ViiV has finally made good on its promise to change the HIV game. The FDA on Thursday approved ViiV’s Cabenuva (cabotegravir and rilpivirine) as a long acting, once-monthly therapy for HIV-positive adults who are virologically suppressed and on a stable antiviral regimen. It’s official: Janet Woodcock is now the acting chief of the FDA. And — according to an Endpoints poll — most industry readers would like her to stay there, although a significant minority is strongly opposed. To recap: Joe Biden is reportedly choosing between Woodcock and former deputy FDA commissioner Joshua Sharfstein as his nominee for the permanent position. Given their respective track records, the decision is set to determine the agency’s lodestar for years to come. The firehose of biopharma news is gushing these days. That’s why broader and deeper is the theme for 2021 at Endpoints. You can expect new coverage outside our core R&D focus, with deeper reporting in some key areas. When John Carroll and I launched Endpoints nearly five years ago, we were wading in waist-high waters. Now we’re a team of 25 full-time staffers (and growing) with plans to cover the flood of biopharma news, Endpoints-style. Close to 2 years ago, GSK’s R&D team eagerly agreed to pay up to $4 billion-plus to ally itself with Merck KGaA on a mid-stage bispecific called bintrafusp alfa, which intrigued them with the combination of a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein. But today the German pharma company says that their lead study on lung cancer was a bust, as independent monitors said there was no reason to believe that the experimental drug — targeting PD-L1/TGF-Beta — could beat Keytruda. It’s time for a new FDA commissioner to come on board, a rite of passage for Joe Biden’s administration that should help seal the new president’s rep on seeking out the experts to lead the government over the next 4 years. As of now, the competition for the top job appears to have narrowed down to 2 people: The longtime CDER chief Janet Woodcock and Joshua Sharfstein, the former principal deputy at the FDA under Peggy Hamburg. Both were appointed by Barack Obama. Tony Coles’ team at Cerevel Therapeutics is adding two high-profile board members, including an ex-governor that has lots of connections to the Boston area where the biotech is based. Former Massachusetts Gov. Deval Patrick is hopping on Cerevel’s board of directors, the company announced Thursday, joining less than three months after Cerevel went public on the backs of Perceptive’s ARYA II SPAC. And in a twist, Pfizer’s new business development chief Deborah Baron is joining the board as well, about three years after the Big Pharma shuttered the neuroscience pipeline that Cerevel is seeking to revive. Eli Lilly says bamlanivimab lowered the risk of contracting symptomatic Covid-19 in a first-of-its-kind trial involving nursing home residents and staff, paving the way for a new option to protect against the virus. But how big of an impact it might have, and what role it will play, at a time vaccines are being rolled out to the exact population it is targeting still remains unclear. Among 965 participants in the study — all of whom tested negative for the coronavirus at baseline — the number of symptomatic cases reported in the bamlanivimab arm was 57% lower than that in the placebo arm (odds ratio 0.43, p=0.00021). In addition to that primary endpoint, all secondary endpoints reached statistical significance. The biopharma industry, on the whole, had a red-letter year in 2020 amid Covid-19, with fundraising at an all-time high and major players speeding vaccines ahead to approval. But for BIO, the industry’s leading trade organization, the pandemic has prompted a reconsideration of the game plan. BIO will pivot to digital as the Covid-19 pandemic continues to rage, making “some staff reductions” as it looks to bring its roughly 37,000 in-person meetings each year to the web, the organization said Thursday.
细胞和基因药物的制造商有了FDA的新指南,它提出了一个泛重复的制造概念。 本指南特别增加了细胞和基因疗法(CGT)的制造,旨在补充美国食品药品监督管理局(FDAS)《良好制造实践条件》对药品和生物制品制造商的要求,以响应COVID-19对药品和生物制品制造商的要求;《企业指南》于2020年6月根据《指南》制定。 指导书中所载的工业专用技术包括从供体中回收的细胞和组织,以及生产CGT产品的各种方法,如细胞培养,病毒还原步骤和成形等。本指南适用于类似于药物和生物产品的CGT产品,但不适用于根据PHS法案第361节重新使用的设备或人细胞,组织和基于细胞或组织的产品(HCT/PS)。 该机构称,目前尚未发现HCT/PS与新型冠状病毒病毒(导致COVID-19的病毒)发生冲突。此外,还不普遍认为通过使用HCT/PS传播病毒。然而,正如美国食品药品监督管理局2020年6月GMP指南(参考文献1)所指出的那样,新型冠状病毒病毒是一种新的冠状病毒,为了确保符合当前良好的生产实践(CGMP)的要求,CGT的生产企业需要评估它是否在其特定的产品,食品,工艺和生产控制条件下具有新的风险。 风险评估的一个关键因素是,在自体或异基因细胞培养过程中,如果感染了新型冠状病毒病毒,它们在细胞培养过程中是否有可能发生大规模的病毒扩散。FDA写道,这可能导致一种含有扩增的SAR-CoV-2病毒负载的体外生产。例如,异基因生产,尤其是来自细胞库的产品,可能比自体生产具有更高的风险。 FDA要求对供体进行常规筛选。FDA提出的结论是基于有限的信息,但包括异基因或自体供体在诱导细胞或组织再生的28天内,是否与Covid-19诱导的Ividal有密切接触,或用Covid-19进行了诊断或阳性试验。 FDA继续建议不要对SAR-CoV-2的渐近供体进行筛选。无论如何,在CGT生产过程中,一个经过验证,清除或改进的测试可以作为风险防范策略的一部分。FDA在指南中补充说,此时,FDA建议不筛查或推迟那些已用非复制,无效或基于RNACOVID-19无效的COVID-19无效的HCT/P供体。 就细胞和组织来源的母体而言,FDA应考虑已知的冠状病毒在普通和组织中的新型冠状病毒,包括冠状病毒在组织中的传播倾向。这是一个不断发展的领域,制造业者应该引用科学文献,为风险评估和风险评估提供依据。 制造风险包括通过良好的医疗卫生和保健实践来降低制造风险。该指南指出,新型冠状病毒已被证明可以在常用的向量生产细胞(如HEK293和Vero细胞)中获得和复制,这一事实是制造商在风险评估和制造策略时应加以权衡的。 指导书中没有任何有关药品检验的说明,但FDA确实说明完全满足CGMP的要求,包括对制造商质量单位的所有评价和质量管理体系中的文件的认可。 FDA已经使该指南在Covid-19的公共卫生发生过程中非常有效,但是该机构仍然在任何时候根据该指南对公共化妆品进行审查。 Social Image Credit:Getty Images RAPS:由Regulatory Affair Professionals Society在Regulatory Focus™上首次发布,Regulatory Affair Professionals Society是全球最大的医疗保健产品回收组织。点击这里获取更多信息。 加拿大皇家银行资本市场 与5AM Ventures联合创始人兼管理合伙人安迪•施瓦布合作 要点 处方数字治疗技术,细胞治疗技术和硅胶药物将是未来治疗模式的重要组成部分。 开发微生物组的潜力可能是更好地诊断疾病所缺少的一环。 学术界,工业界和风险投资之间日益紧密的联系正在催生出更多创新的生物技术公司。 生物技术现在被投资者视为一个增长空间,同时也是一个安全的避风港,推动了最近的IPO热潮。 葛兰素史克公司HIV病毒第VIV单元在2019年末遭受了惨痛的损失,当时FDA基于生产问题对其每月注射一次的申请急刹车。现在,有了这个障碍,ViiV终于兑现了改变HIV游戏的承诺。 FDA周四批准VIIVS Cabenuva(卡博特格拉韦和利匹韦林)作为长期的,每月一次的治疗方案,用于病毒学受抑制且使用稳定的抗病毒方案的HIV阳性成人。 ITS官员:珍妮特·伍德科克现在是FDA的代理局长。 根据Endpoints的一项民意调查,大多数行业读者都希望她留在那里,尽管有相当一部分人强烈反对。 重述一下:据报道,乔·拜登正在伍德科克和前FDA副专员约书亚·沙夫斯坦之间选择他的永久职位提名人。鉴于它们各自的成绩记录,这一决定将确定原子能机构今后几年的方向。 这几天生物制药新闻的火龙喷涌而出。 这就是为什么2021年的主题更广泛,更深入。你可以期待我们的核心研发重点之外的新报道,在一些关键领域有更深入的报道。大约五年前,当约翰·卡罗尔和我推出Endpoints的时候,我们正趟着一条不起眼的水路。现在我们有一个由25名全职员工组成的团队(并且还在不断增长),计划覆盖生物制药新闻的洪流,终点式的。 将近两年前,GSKS的研发团队急切地同意支付高达40多亿美元与默克集团联合研制一种名为bintrafusp alfa的中期双特异性药物,该药物将TGF?陷阱与一种融合蛋白中的抗PD-L1机制结合在一起,引起了他们的兴趣。 但今天这家德国制药公司表示,他们在肺癌方面的领先研究是失败的,因为独立的监督员说,没有理由相信靶向PD-L1/TGF-beta的试验性药物能够打败Keytruda。 现在是时候让一位新的FDA专员上任了,这是乔·比登政府的一个成人仪式,这将有助于确定新总统在未来4年中寻找专家来领导政府的代表。 到目前为止,最高职位的竞争似乎已经缩小到了两个人:长期担任CDER主席的珍妮特·伍德科克和曾在佩吉·汉堡领导下担任FDA首席副手的约书亚·夏夫斯坦(Joshua Sharfstein)。两人都是由巴拉克·奥巴马任命的。 Cerevel Therapeutics的Tony Colesteam将增加两名高知名度的董事会成员,其中包括一名前州长,他与该生物技术公司所在的波士顿地区有很多联系。 Cerevel公司周四宣布,前马萨诸塞州州长德瓦尔•帕特里克将加入该公司董事会,而在不到三个月前,Cerevel公司在艾雅二世公司的支持下上市。此外,Pfizer新的业务发展主管黛博拉·巴伦也加入了董事会,大约三年前,这家大型制药公司关闭了Cerevel正在寻求重振的神经科学项目。 礼来公司表示,在一项涉及疗养院居民和工作人员的首次同类试验中,班拉尼单抗降低了感染有症状的柯维19病毒的风险,为预防病毒的新选择铺平了道路。 但在疫苗正向其针对的确切人群推出之际,它可能会产生多大影响,以及它将发挥何种作用,目前仍不清楚。 在965名基线冠状病毒检测呈阴性的研究参与者中,班拉维单抗组报告的有症状病例数比安慰剂组低57%(优势比0.43,P=0.00021)。除主要终点外,所有次要终点均达到统计学意义。 总体而言,生物制药行业在2020年的Covid-19中迎来了喜人的一年,筹资达到了历史最高水平,各大公司加快了疫苗的审批速度。但对于该行业的主要贸易组织BIO来说,这场大流行促使他们重新考虑自己的游戏计划。 该组织周四表示,随着Covid-19疫情的持续肆虐,BIO将转向数字化,并将裁减一些员工,以实现每年约37,000次面对面会议的网络化。

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