By Patrick Wingrove
作者：帕特里克·溫格羅夫
Oct 4 (Reuters) - One of the Largest Contract Drug Manufacturing Plants in the U.S. Owned by Thermo Fisher Scientific Tmo.n Over the Past 10 Years Has Repeatedly Breached Rules Meant to Ensure Drugs Are Free of Contamination, FDA Documents Show, Including Twice This Year.
10月4日（路透社）— 賽默飛世爾科學旗下的美國最大的合同藥物製造工廠之一 TMON。 美國食品藥品管理局的文件顯示，在過去的10年中，一再違反旨在確保藥物不受污染的規定，包括今年的兩次。
The Most Recent U.S. Food and Drug Administration Inspection of Thermo Fisher's Greenville Plant in May Identified Manufacturing Issues for the Respiratory Syncytial Virus Drug Beyfortus, a Preventive Antibody Therapy From AstraZeneca Azn.l and Sanofi Sasy.pa for Infants and Toddlers.
美國食品藥品監督管理局最近於5月對賽默飛世爾格林維爾工廠進行了檢查，發現了呼吸道合胞病毒藥物Beyfortus的生產問題，該藥物是阿斯利康的預防性抗體療法 azn.l 還有賽諾菲 Sasy.pa 適用於嬰兒和幼兒。
The Issues Were Resolved to the FDA's Satisfaction, the FDA and Sanofi Said. There Is No Evidence That These Manufacturing Issues Have Resulted in Harm to Patients.
美國食品藥品管理局和賽諾菲表示，這些問題的解決令美國食品藥品管理局滿意。沒有證據表明這些製造問題對患者造成了傷害。
The 1.7 Million Square Foot Plant Makes Around 40 Different Medicines, According to the FDA's National Drugs Directory, Including Life Saving Hospital-Administered and Pharmacy Drugs and Novo Nordisk's Novob.co Weight-Loss Medicine Wegovy. Thermo Fisher Bought the Plant in 2017 With Its Acquisition of Contract Manufacturer Patheon.
根據美國食品藥品管理局的國家藥品名錄，這座佔地170萬平方英尺的工廠生產約40種不同的藥物，包括救生用醫院用藥和藥房藥物，以及諾和諾德的藥物 novob.co 減肥藥物 Wegovy。賽默費舍爾於2017年收購了合同製造商Patheon，收購了該工廠。
Growth in Obesity Medicines and Complex Biologic Therapies Is Fueling Demand for U.S. Contract Manufacturers Like Thermo Fisher. but Two Manufacturing Experts Say the Plant's 10-Year Audit Record Gives Them Reason to Be Concerned About the Company's Approach to Quality Control.
肥胖藥物和複雜生物療法的增長推動了對Thermo Fisher等美國合同製造商的需求。但兩位製造業專家表示，該工廠的10年審計記錄使他們有理由對該公司的質量控制方法感到擔憂。
"There Are Multiple Issues With the Culture of the Organization. They Are Not Looking at the Long Term and Have a Fix-When-Caught Mentality Versus a Culture of Prevention," Said David Talmage, Vice President of Education at the Parenteral Drug Association, Which Provides Training on Best Practices for Sterile Manufacturing.
「本組織的文化存在多個問題。他們不是着眼長遠，而是抱着 「一抓就解決」 的心態，而不是預防文化。」 腸外藥物協會教育副總裁戴維·塔爾米奇說，該協會提供無菌生產最佳實踐培訓。
The FDA's Inspection of the Beyfortus Production Line Found That Required Manufacturing Processes Fell Short in Areas Such as Ensuring Some Equipment Was Sufficiently Sterilized, According to a Report Obtained by Reuters Through a Freedom of Information Act (Foia) Request.
路透社通過《信息自由法》（Foia）要求獲得的一份報告顯示，美國食品和藥物管理局對Beyfortus生產線的檢查發現，在確保某些設備經過充分消毒等領域，所需的製造工藝不足。
A Spokesperson for Sanofi, Which Markets Beyfortus in the U.S. Where It Was Approved Last Year, Said the FDA's Findings Were All Addressed and Subsequently Reviewed by the Regulator. the FDA Approved the Beyfortus Doses Before They Left the Plant for Sale, the Spokesperson Said.
賽諾菲的發言人表示，美國食品藥品管理局的調查結果均已處理完畢，隨後由監管機構進行了審查。該發言人說，美國食品藥品管理局在Beyfortus的劑量離開工廠銷售之前批准了該劑量。
Sandy Pound, Chief Communications Officer at Thermo Fisher, Said the Company Participates in More Than 1,000 Regulator and Customer Inspections Every Year and Takes Regulator Observations Seriously. She Did Not Comment on the Specifics of the FDA Audit.
賽默飛世爾首席傳播官桑迪·龐德表示，該公司每年參與1,000多次監管機構和客戶檢查，並認真對待監管機構的觀察。她沒有對美國食品和藥物管理局審計的細節發表評論。
FDA Report
FDA 報告
the FDA Report Noted 17 Shortfalls During the Beyfortus Audit Including Inadequate Visual Inspections for Any Particulate Matter Floating in Injectable Drugs and Problems With How Staff Handled Sterile Components.
美國食品藥品管理局的報告指出了Beyfortus審計期間的17個缺陷，包括對可注射藥物中漂浮的任何顆粒物的目視檢查不足，以及工作人員處理無菌成分的方式存在問題。
One Issue Identified Was Thermo Fisher Had Not Provided the Studies Backing up How It Measured and Set Thresholds for Bubbles That Can Occur in Injectable Medicine. Such Bubbles Can Cause Deadly Blood Blockages in Veins or Arteries.
發現的一個問題是，Thermo Fisher沒有提供研究來支持其如何測量和設置注射藥物中可能出現的氣泡閾值。這樣的氣泡會導致靜脈或動脈中致命的血液阻塞。
The FDA Said in a Statement That It Had Audited the Plant for Cause Related to Certain FDA Approved Products at the Site and Did Not Take or Recommend Regulatory or Enforcement Action, Saying It Was Not Warranted at This Time.
美國食品藥品管理局在一份聲明中表示，它已對該工廠進行了審計，原因與該工廠的某些FDA批准的產品有關，沒有采取或建議採取監管或執法行動，稱目前沒有根據。
Most Concerns Raised in FDA Manufacturing Audits Are Solved, as This One Was, Through Agreement With the Company. the FDA Can Take Action When Companies Are Uncooperative or Do Not Make Corrections Fast Enough or to Its Satisfaction.
美國食品和藥物管理局製造業審計中提出的大多數擔憂都可以通過與該公司的協議得到解決。當公司不合作或做出更正的速度不夠快或不滿意時，FDA可以採取行動。
The Agency Said the Manufacturer Had Provided Information on Several Matters Including Control of Bubble Size and Information on Allowable Bubble Size From a Safety Standpoint. the FDA Added That the Facility Had "Adequately Addressed Its Concerns."
該機構表示，該製造商已經提供了有關多個事項的信息，包括氣泡大小的控制以及從安全角度看允許的氣泡大小的信息。美國食品和藥物管理局補充說，該設施 「已充分解決了其擔憂」。
The FDA Did Not Comment When Asked if Patients Had Been Harmed as a Result of the Lapses.
當被問及患者是否因失誤而受到傷害時，美國食品藥品管理局沒有發表評論。
the Medicines Found to Be at Issue in Five Other FDA Audits From 2014 Through February This Year, Were Not Identified in Regulatory Reports Obtained by Reuters. It Has Inspected the Plant at Least 10 Times in the Past 10 Years.
路透社獲得的監管報告未指明在2014年至今年2月的其他五項美國食品藥品管理局審計中發現的有爭議的藥物。在過去的10年中，它至少對該工廠進行了10次檢查。
The FDA Conducts Thousands of Audits per Year but Time Between Visits to a Plant Varies. It Does Prioritize Plants With Sterile Manufacturing Operations Such as This One.
美國食品和藥物管理局每年進行數千次審計，但兩次訪問工廠的時間各不相同。它確實會優先考慮像這樣的無菌製造業務的工廠。
Three Experts Who Reviewed the FDA Documents Said They Were Concerned That Staff Had Not Followed Procedures to Prevent Microbial Contamination, Including Sufficiently Sterilizing the Equipment Used to Seal Drugs and Prevent Leakage.
三位審查美國食品藥品管理局文件的專家表示，他們擔心工作人員沒有遵守防止微生物污染的程序，包括對用於密封藥品和防止泄漏的設備進行充分消毒。
Steven Lynn, a Former Head of the FDA's Office of Manufacturing and Product Quality Who Is Now a Regulatory Compliance Consultant, Said the Problems With Thermo Fisher's Checks for Bubble Size Was One of the More Troubling Findings.
美國食品藥品管理局製造和產品質量辦公室前負責人、現爲監管合規顧問的史蒂芬·林恩說，賽默飛世爾氣泡大小檢查的問題是最令人不安的發現之一。
Vaccines, Too
疫苗也是
the FDA First Inspected the Plant This Year in February, According to a Separate Report Obtained by Reuters Through Foia, Targeting Covid and Flu Vaccines, Which Are Given in the Fall When Respiratory Diseases Circulate.
根據路透社通過Foia獲得的另一份報告，美國食品藥品管理局於今年2月首次檢查了該工廠，該報告針對的是Covid和流感疫苗，這些疫苗是在呼吸系統疾病流行的秋季接種的。
the Regulator Returned in May With the Aim of Auditing Production of Beyfortus, Moderna's Mrna.o Covid-19 Vaccine, and Two Flu Vaccines Made by Australia's CSL Csl.ax, According to a Source Familiar With the Matter Who Was Not Authorized to Speak.
監管機構於5月回歸，目的是對Moderna的Beyfortus的生產進行審計 mrna.o Covid-19疫苗和澳大利亞CSL生產的兩種流感疫苗 csl.ax，一位熟悉此事但無權發言的消息人士稱。
Moderna and CSL Both Said They Were Not Manufacturing Vaccines at That Plant During Either FDA Visit.
在兩次美國食品藥品管理局訪問期間，Moderna和CSL都表示，他們沒有在該工廠生產疫苗。
Thermo Fisher's Greenville Plant Received $49 Million From the U.S. Department of Defense in 2020 to Help Make Covid Vaccines and Is One of the Latest Government-Funded Factories Found to Have Fallen Short of FDA Manufacturing Standards.
賽默飛世爾的格林維爾工廠在2020年從美國國防部獲得了4900萬美元的資金，用於幫助生產Covid疫苗，並且是最新發現的由政府資助的工廠之一 未達到 FDA 製造標準。
Thermo Fisher's Manufacturing Business, Which Operates as Patheon and Includes More Than 60 Plants in 24 Countries, Makes up Around $8 Billion, or 19%, of Its $42.8 Billion Annual Revenue.
賽默飛世爾的製造業務以萬神殿的名義運營，包括分佈在24個國家的60多家工廠，佔其年收入428億美元的約80億美元，佔19％。
Thermo Fisher Competes With Contract Manufacturing Firms Lonza Lonn.s and Catalent Ctlt.n, Which Has Agreed to Be Bought by Novo Nordisk.
Thermo Fisher 與合同製造公司 Lonza 競爭 Lonn.s 還有 Catalent ctlt.n，它已同意被諾和諾德收購。
"Contract Manufacturing Will Likely Continue to Be an Above Market Growth Driver for Thermo (Partly) Because of the Underlying Market Demand," Said Deutsche Bank Analyst Justin Bowers.
德意志銀行分析師賈斯汀·鮑爾斯表示：「合同製造可能會繼續成爲Thermo高於市場的增長驅動力（部分原因），這是由於潛在的市場需求。」
(Reporting by Patrick Wingrove in New York; Additional Reporting by Maggie Fick in London; Editing by Caroline Humer and Anna Driver)
（帕特里克·溫格羅夫在紐約的報道；瑪姬·菲克在倫敦的補充報道；卡羅琳·胡默和安娜·德勒編輯）