By Patrick Wingrove
作者Patrick Wingrove
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.
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.
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對賽默飛世爾在五月份的格林維爾工廠進行的檢查發現了生產問題，涉及了阿斯利康的預防性抗體治療藥物Beyfortus的呼吸道合胞病毒藥物 Azn.l 和賽諾菲安萬特 Merck KGaA 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.
這些問題已得到美國食品藥品監督管理局及賽諾菲安萬特的滿意解決。沒有證據表明這些生產問題導致了對患者的傷害。
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.
這座佔170萬平方英尺的工廠生產大約40種不同的藥品，包括救生醫院用藥和藥店用藥，以及諾和諾德的 Novob.co 減肥藥物Wegovy。賽默飛世爾在2017年收購代工廠商巴泰昂時購得該工廠。
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製劑的增長推動了對像賽默飛世爾這樣的美國代工廠商的需求。但兩位製造業專家稱，該工廠10年的審計記錄讓他們對公司對質量控制的方法感到擔憂。
"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.
「該組織文化存在多個問題。他們缺乏長期眼光，採取的是事後解決方案而不是預防爲主的文化，」負責提供有關無菌製造最佳實踐培訓的美國無菌藥品協會教育副總裁大衛·塔爾馬吉說。
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.
根據《路透社》通過信息自由法（Foia）申請獲得的報告，美國食品藥品監督管理局對Beyfortus生產線的檢查發現，在確保部分設備徹底消毒等方面，所需的製造流程存在不足之處。
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.
賽諾菲在美國市場推廣Beyfortus，在去年獲得批准。一位該公司發言人表示，美國食品藥品監督管理局的發現已全部得到解決，並得到監管機構的審查。該發言人表示，FDA在售出Beyfortus藥量前已批准該藥量。
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.
賽默飛世爾首席通信官桑迪·龐德表示，公司每年參與超過1000次的監管和客戶檢查，並認真對待監管機構的觀察。她沒有對FDA審計的具體細節發表評論。
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.
FDA報告指出，在Beyfortus審計中出現了17個缺陷，包括注射藥物中漂浮的任何微粒的視覺檢查不足以及工作人員處理無菌元件的問題。
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.
賽默飛世爾未提供支持其測量和設定可發生在注射藥物中的氣泡閾值的研究，這類氣泡可能導致靜脈或動脈中致命的血栓堵塞。
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.
美國食品藥品監督管理局在一份聲明中表示，已對該工廠進行了審計，針對該地點與某些FDA批准的產品相關的原因，並未採取或建議進行監管或執法行動，稱目前沒有必要。
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.
美國食品藥品監督管理局的製造審計中提出的大多數問題，包括這個問題，在與公司達成一致後得到解決。當公司不合作或未能及時或令人滿意地進行修正時，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，製造商就多個問題提供了信息，包括控制氣泡大小的信息以及從安全角度允許的氣泡大小信息。FDA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.
當被問及是否有患者由於疏忽而受傷時，FDA未發表評論。
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.
從2014年到今年二月，另外五次FDA審計中發現存在問題的藥品，在路透社獲得的監管報告中未被確認。在過去10年中，至少已對該工廠進行了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.
FDA每年進行成千上萬次審計，但對工廠訪問之間的時間間隔有所不同。它會優先考慮具有類似這種無菌製造操作的工廠。
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.
審查FDA文件的三位專家表示，他們擔心員工未遵循防止微生物污染的程序，包括充分對密封藥物的設備進行滅菌和防止泄漏。
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.
史蒂文·林（Steven Lynn）是FDA製造和產品質量辦公室的前負責人，現在是監管合規顧問，他表示賽默飛世爾（Thermo Fisher）對氣泡大小的檢查問題是比較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.
據路透社通過Foia獲得的另一份報告顯示，FDA今年2月首次檢查了該工廠，重點針對秋季呼吸道疾病盛行時預防的新冠和流感疫苗。
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.
監管機構在五月回訪，審計了Moderna的貝福特斯（Beyfortus）產量，以及澳洲CSL製造的兩種流感疫苗。 Mrna.o 新冠病毒疫苗以及兩種由澳洲CSL製造的流感疫苗。 Csl.ax根據知情人士透露，未經授權發言。
Moderna and CSL Both Said They Were Not Manufacturing Vaccines at That Plant During Either FDA Visit.
Moderna和CSL均表示他們在FDA訪問期間未在該工廠製造疫苗。
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.
2020年Thermo Fisher的格林維爾工廠從美國國防部獲得4900萬美元，用於生產新冠疫苗，是最新發現的未達到FDA製造標準的政府資助工廠之一。 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.
Thermo Fisher的製造業務，作爲Patheon運營，在24個國家的60多家工廠中佔其428億美元年收入的約80億美元，約佔其全年營業收入的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與代工廠商龍沙競爭。 Lonn.s 和catalent 公司 Ctlt.n，該公司已同意被 Novo Nordisk 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.
「代工廠商很可能會繼續成爲 賽默飛世爾 的市場增長引擎之一，部分原因是潛在市場需求，」 德意志銀行 分析師 Justin Bowers 表示。
(Reporting by Patrick Wingrove in New York; Additional Reporting by Maggie Fick in London; Editing by Caroline Humer and Anna Driver)
（紐約 Patrick Wingrove 報道；倫敦 Maggie Fick 補充報道；Caroline Humer 和 Anna Driver 編輯）