FDA slaps Flori da's Al lay Phar ma ceu ti cals with warn ing let ter over vague re spons es to drug po ten cy is sues

FDA对Flori Da的Al lay Phar ma ceu ti cals发出警告,警告其对药品的模糊解释

2021-02-13 05:00:11 ENDPOINTS NEWS

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In­ad­e­quate re­spons­es to find­ings of po­ten­cy dis­crep­an­cies, blend­ing is­sues and out-of-spec­i­fi­ca­tion sam­ples dur­ing a May 2020 in­spec­tion re­cent­ly land­ed tablet man­u­fac­tur­er Al­lay Phar­ma­ceu­ti­cals with a scorch­ing FDA warn­ing let­ter. In a heav­i­ly-redact­ed ver­sion of the Jan 27 let­ter that was made avail­able this week, the FDA chid­ed the Hialeah, Flori­da man­u­fac­tur­er for vague and in­suf­fi­cient re­spons­es across the board to three ma­jor ob­ser­va­tions dis­cov­ered dur­ing the May 5 to 15, 2020 site in­spec­tion. Those ob­ser­va­tions were com­mu­ni­cat­ed through a Form 483 let­ter, and Al­lay’s re­spons­es to the FDA on June 6 clear­ly irked the agency. Most no­tably, the FDA took is­sue with the fact that Al­lay ei­ther doesn’t have, or didn’t pro­vide, suf­fi­cient da­ta that could ex­plain why the tablet sam­ples of an un­named drug that were tak­en dur­ing the site in­spec­tion last year were be­low nec­es­sary po­ten­cy stan­dards and var­ied in what po­ten­cy they had. “Your man­u­fac­tur­ing fail­ures in­di­cate that you do not have an ad­e­quate on­go­ing pro­gram for mon­i­tor­ing process con­trol to en­sure sta­ble man­u­fac­tur­ing op­er­a­tions and con­sis­tent drug qual­i­ty,” the FDA wrote, lat­er urg­ing the com­pa­ny to con­sult with a cGMP ex­pert to bring its stan­dards up to code. While it’s un­clear ex­act­ly how many drugs the FDA ob­ser­va­tions are re­lat­ed to, Al­lay is un­der con­tract to pro­duce at least one tablet with a com­pa­ny whose name is al­so redact­ed. Re­gard­less of what oth­er terms the two groups agreed to, the FDA made clear to Al­lay that it is re­spon­si­ble for meet­ing qual­i­ty stan­dards, which it hasn’t done or in­ves­ti­gat­ed in a thor­ough man­ner. “In the qual­i­ty agree­ment with the prod­uct own­er, you have the pri­ma­ry re­spon­si­bil­i­ty for in­ves­ti­gat­ing (out-of-spec­i­fi­ca­tion) re­sults,” the let­ter reads. “Your in­ves­ti­ga­tion in­to the OOS sam­ple re­sult was in­ad­e­quate and did not iden­ti­fy (Cor­rec­tive Ac­tion and Pre­ven­tive Ac­tion). Fur­ther­more, an in­ves­ti­ga­tion was not per­formed to en­sure that pre­vi­ous­ly re­leased lots met your re­vised as­say spec­i­fi­ca­tions. FDA in­ves­ti­ga­tors found 13 lots with­in ex­piry that ex­ceed­ed your new as­say spec­i­fi­ca­tion dur­ing re­lease or sta­bil­i­ty test­ing. These lots should have been iden­ti­fied in your in­ves­ti­ga­tion.” The FDA al­so high­light­ed test­ing er­rors and dis­crep­an­cies for ac­tive phar­ma­ceu­ti­cal in­gre­di­ents, call­ing out test­ing re­sults that didn’t match up to those quot­ed by a new API man­u­fac­tur­er used by Al­lay. In one in­stance, the com­pa­ny’s tests on an API lot dif­fered by 7.8% com­pared to the rate quot­ed by the in­gre­di­ent mak­er, but Al­lay went ahead with man­u­fac­tur­ing its drug any­way, the FDA said. Al­lay is now re­quired to pro­vide the FDA with a re­view of all oth­er prod­ucts it man­u­fac­tures, re­gard­less of whether the prod­ucts were iden­ti­fied in the Form 483 ob­ser­va­tions, as well as a “com­pre­hen­sive and in­de­pen­dent” as­sess­ment es­sen­tial­ly of its en­tire sys­tem for ad­dress­ing de­vi­a­tions from cGMP man­u­fac­tur­ing process­es. Al­lay has 15 busi­ness days (Feb. 18) to re­spond to the FDA’s warn­ing let­ter. The com­pa­ny did not im­me­di­ate­ly re­turn a re­quest from End­points News seek­ing com­ment. Avance Clinical is the leading Australian CRO for biotechs, and a Frost & Sullivan Asia-Pacific CRO Market Leadership Award winner. Avance Clinical is a full-service CRO with 24-years of experience, led by CEO Yvonne Lungershausen who is recognised as co-founder of Australia’s clinical research industry. The company has deep expertise, as well as extensive partnerships with technology leaders including Medidata, Oracle, and Medrio to deliver the region’s best clinical trial services to its biotech clients. Avance Clinical grew more than 57% in 2020 and has more than doubled staff numbers. Astellas and Seagen made a big splash with their Nectin-4 targeting therapy Padcev in late 2019, scoring a conditional FDA approval to target urothelial cancer. Now, the results are in for the confirmatory study for that indication, and it looks like a resounding win for Padcev. Astellas and Seagen’s Padcev extended patients’ lives to an average 12.9 months compared with nine months for a chemo control, according to full data from the Phase III EV-301 study presented Friday at the virtual ASCO GU meeting. Amicus stock got hammered Thursday afternoon after the biotech put out word that the crown jewel in the pipeline just failed the primary endpoint in a head-to-head study with the standard of care for Pompe disease. CEO John Crowley, though, has a long track record at spotlighting the positive, which was on full display in its statement on the failed study. Researchers for the company highlighted some marginally positive secondary data with an improvement in respiratory function from a post hoc analysis that they plan to roll ahead to the FDA. Eli Lilly let go of former CFO Josh Smiley earlier this week, and it apparently had good reason to do so after the veteran finance chief reportedly sent inappropriate messages to employees. But the firing came with a special poke in the eye for Smiley, who will be forced to forfeit $24 million in compensation as he walks out the door. According to an SEC filing, Lilly required Smiley to forgo $1 million of his 2020 cash bonus, around $3 million of his due shareholder value awards the past three years, and all other current and future equity incentive awards as part of his severance deal— which in aggregate total more than $24 million in future payouts wiped away. In a coda to a six-year legal fight on the PCSK9 terrain, the US Federal Court of Appeals has ruled that Amgen’s patent claims for PCSK9 antibodies as a class are invalid, handing a win to Sanofi and Regeneron. The implications, though, may reverberate far beyond Amgen. The Thousand Oaks, CA-based company, whose Repatha was approved a month after Praluent in 2015, may take comfort in the fact that its sales have consistently eclipsed Sanofi or Regeneron’s, although neither has climbed anywhere near the blockbuster expectations developers and analysts had. As the obesity epidemic in America worsened throughout the years, many biotechs cropped up hoping to develop weight-loss drugs that would help stem this tide. But now, Novo Nordisk’s diabetes cash cow semaglutide is showing such startlingly effective results in obesity that it may have a head start in cornering the market. In nearly a 2,000-person trial, participants injected themselves with either semaglutide or placebo for 68 weeks. Patients in the drug arm saw an average 15% weight loss, compared with just 2.4% on placebo, and almost a third lost more than 20% of their weight. Researchers published the data Wednesday in the New England Journal of Medicine, and all p-values came out to p<0.001. Gilead’s battle-scarred alliance with Galapagos just suffered another grievous wound. The biotech partners reported Wednesday morning that they are abandoning their late-stage pivotal program for ziritaxestat (GLPG1690) — along with everything else in the clinic — after the drug failed a futility analysis, the latest in a series of big setbacks to afflict these players. This drug was at the heart of Dan O’Day’s revised alliance with Galapagos back in the summer of 2019, as the then newly-named Gilead CEO looked to diversify the pipeline and satisfy analysts’ demands for a broader product portfolio with what he called a “transformative” pact. Gilead paid close to $5 billion in an upfront and equity investment for that deal, which now largely lies in ruin. Maribavir, once a trial dud and multiple-time castoff, received new life from the FDA right before Takeda picked up Shire in 2019. Now, Takeda is posting winning late-stage data from the drug that could help it succeed where so many others have failed. In a 352-person trial comparing maribavir to physician’s choice antivirals, more than twice as many patients on maribavir achieved CMV viremia clearance at eight weeks — the study’s primary endpoint, according to Takeda. Of the 235 patients who received maribavir, 131 (or 55.7%) achieved clearance versus 28 of 117 (or 23.9%) of those on conventional antiviral therapies (p<0.001). Viremia is the isolation of CMV by culture. Almost three months after leaving Vividion Therapeutics, where he recently signed a $135 million Roche deal, Diego Miralles has landed the top spot on a “dream team.” On Thursday, Flagship Pioneering officially tapped Miralles as its newest CEO-partner, where he’ll head the stealthy portfolio company Laronde. While Miralles couldn’t say much about Laronde just yet, Flagship has said it’s an early-stage biotech working on nucleic acid medicines using a “multi-modality eRNA platform.”
在2020年5月的一份符合标准的平板电脑制造商的报告中,我们需要找到一些不符合标准的产品,并将其与一份美国食品和药物管理局发出的警告信联系起来,以便找到符合标准的产品和不符合标准的产品。 在这周对1月27日的信进行的一次详细审查中,FDA对三个关于2020年5月5日至15日的网站的声明进行了详细审查。这些服务是通过483表单的一封信被查到的,艾利公司6月6日给FDA的信显然让FDA很恼火。 最不确定的是,FDA采取的是起诉的事实,即他们没有,或没有提供,可以说明为什么去年在该网站上使用的一种未命名药物的片剂样本是低的,并且在它们拥有的产品中存在差异。 FDA写道:“你的男人不合格,是因为你没有一个正确的过程控制程序来确保男人不合格和药品质量。”随后,该公司将与cGMP专家进行协商,以使其标准符合规范。 虽然目前还不清楚FDA的药品有多少种,但阿莱公司不愿提供至少一种药片,而药片的名称也是如此修改过的公司名称。(译者注:美国食品药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局的药品监督管理局。除了两个小组同意的条款外,FDA向Allay明确表示,它有责任满足质量标准,但它没有做到这一点,也没有做到这一点。 信中写道:“在与产品所有者达成质量一致的情况下,你就有了不符合标准(不符合标准)的标准。”“你对OOS SAM的反应是正确的,而不是正确的(反应和预反应)。此外,还没有形成一个标准,以确保以前租赁的地段符合你的要求。FDA的专家们发现了13个批批,这些批批将你的新产品重新租赁或测试。这些东西本应该在你的衣服上注明的。“ 美国食品和药物管理局对活性物质的高光检测结果与试验结果不一致,而试验结果与试验结果不一致,而试验结果与试验结果不一致,而试验结果与试验结果不一致,试验结果与试验结果不一致,试验结果与试验结果不一致,试验结果与试验结果不一致,试验结果与试验结果不一致。FDA说,在一个方面,该公司对一批原料药的检测结果与该公司的检测结果相差了7.8%,但该公司还是以任何方式对其药品进行了检测。 现在,艾利公司被要求向FDA提交一份关于所有其他产品的报告,不包括这些产品是否在483表单中被确认,以及一份关于其从cGMP表单中确认产品的“预确认和预确认”系统的报告。 艾利有15个营业日(2月18日)来回复FDA的警告信。该公司并没有从“终点新闻搜索”公司重新进行搜索。 Avance Clinical是澳大利亚领先的生物技术CRO公司,也是Frost&Sullivan亚太地区CRO市场领导奖获得者。Avance Clinical是一家提供全方位服务的CRO,拥有24年的经验,由首席执行官Yvonne Lungershausen领导,他是澳大利亚临床研究行业的共同创始人。该公司拥有深厚的专业知识,并与包括Medidata、Oracle和Medrio在内的技术领先者建立了广泛的合作伙伴关系,为其生物技术客户提供该地区最好的临床试验服务。Avance Clinical在2020年增长超过57%,员工人数增加了一倍多。 Astellas和Seagen在2019年末推出了Nectin-4靶向疗法Padcev,获得FDA有条件批准,用于靶向尿路上皮癌。现在,该研究的结果正在进行验证性研究,这对帕德切夫来说似乎是一个巨大的胜利。 根据Astellas和Seagen的Padcev将患者的平均寿命延长到12.9个月,而化疗控制的患者平均寿命为9个月,这是周五在虚拟ASCO GU会议上公布的第三阶段EV-301研究的完整数据。 Amicus公司周四下午遭到重创,此前该生物技术公司发布消息称,在庞贝病护理标准的一项面对面研究中,这颗正在酝酿中的皇冠上的明珠刚刚未能达到主要终点。 然而,首席执行官约翰•克劳利在强调积极方面有着悠久的历史记录,这一点在其关于失败研究的声明中得到了充分展示。该公司的研究人员从一项事后分析中强调了一些轻微积极的辅助数据,即呼吸功能的改善,他们计划将这些数据提交给FDA。 本周早些时候,礼来公司解雇了前首席财务官乔希•斯迈利,在这位资深财务主管据报道向员工发送不当信息后,礼来公司显然有充分的理由这么做。但这次解雇对斯迈利来说是一个特别的打击,他将被迫在走出房门时被没收2400万美元的赔偿金。 根据SEC的一份文件,礼来要求斯迈利放弃其2020年的100万美元现金奖金、过去三年到期的约300万美元股东价值奖励,以及作为其离职协议的一部分的所有其他当前和未来股权激励奖励--这些奖金总计超过2400万美元的未来支付被抹掉。 在PCSK9领域长达六年的法律斗争中,美国联邦上诉法院裁定安进公司将PCSK9抗体作为一类的专利主张无效,赛诺菲和再生龙赢得了胜利。 然而,其影响可能远远超出了安进的范围。 这家总部位于加利福尼亚州千橡市的公司,其Repatha在2015年比Praluent晚一个月获得批准,或许会感到欣慰的是,该公司的销售额一直超过赛诺菲或Regeneron公司,尽管这两家公司的销售额都没有达到开发商和分析师的预期。 随着肥胖症在美国的蔓延,多年来不断恶化,许多生物技术公司突然出现,希望能开发出减肥药来帮助遏制这一趋势。但现在,诺和诺德的糖尿病摇钱树semaglutide在肥胖方面显示出惊人的有效效果,它可能在市场上占了先机。 在一项近2000人的试验中,参与者给自己注射semaglutide或安慰剂,持续68周。服用药物的患者平均体重减轻了15%,而服用安慰剂的患者仅为2.4%,几乎三分之一的患者体重减轻了20%以上。研究人员在周三的《新英格兰医学杂志》上发表了这一数据,所有的P值均为P<0.001。 基列与加拉帕戈斯的战斗伤痕累累的联盟刚刚遭受了另一个严重的创伤。 这两家生物技术合作伙伴周三早间报告说,他们将放弃锆英司他酯(GLPG1690)的后期关键项目--以及诊所里的其他所有项目--因为该药物没有通过无效性分析,这是困扰这些公司的一系列重大挫折中的最新一例。 这种药物是丹·奥戴(Dan O'Day)在2019年夏天与加拉帕戈斯修订后的联盟的核心,当时这位刚上任的Gilead首席执行官希望通过一项他称之为“变革性”的协议,使管道多样化,并满足分析师对更广泛产品组合的需求。Gilead为这笔交易支付了近50亿美元的前期投资和股权投资,现在这笔交易基本上已经破产。 马里巴韦,曾经是一个试验哑弹和多次丢弃,在2019年竹田接手夏尔之前,从FDA获得了新生。现在,武田公布了从药物中获得的后期数据,这些数据可以帮助它在许多其他药物失败的地方取得成功。 根据Takeda的说法,在一项352人的试验中,比较了maribavir和医生选择的抗病毒药物,使用maribavir的患者在8周时达到CMV病毒血症清除率的两倍多,这是该研究的主要终点。在接受马里巴韦治疗的235例患者中,131例(55.7%)获得清除,而在接受常规抗病毒治疗的117例患者中,28例(23.9%)获得清除(P<0.001)。病毒血症是通过培养分离CMV。 在离开Vividion Therapeutics公司近三个月后,迭戈·米拉莱斯已经登上了“梦之队”的榜首位置。他最近在Vividion Therapeutics与罗氏公司签下了一份1.35亿美元的合同。 本周四,旗舰创业公司正式任命米拉莱斯为其最新的首席执行官合伙人,他将领导秘密投资组合公司Laronde。虽然Miralles还不能对Laronde说太多,但旗舰公司已经表示,这是一种利用“多模态eRNA平台”开发核酸药物的早期生物技术。

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