Work Hard to Ensure Food,Drugs Safety for the People——An interview with Shao Mingli,director-general of the State Food and Drug Administration(SFDA)

Following is an interview given by Shao Mingli, director-general of China＇s State Food and Drug Administration to our reporter on what is being done to ensure food and drug safety in China. As everybody knows, food and drug safety is vital to people＇s lives.

The State Food and Drug Administration:Supervisory Regulations on Cosmetics May Be Introduced This Year

On May 28, 2019 Chinese Cosmetics Development Conference was held in Beijing. At the conference, Li Nan, chief of the General Division, Supervision Department of the State Food and Drug Administration introduced China’s development concerning the cosmetics supervisory rules and regulations from the perspectives of legislation plan and thinking. He mentioned that the regulations on supervision and administration of cosmetics are expected to be released this year, and the regulations on cosmetic registration and label management.

美国食品药物管理总局(FOOD AND DRUG ADMINISTRATION,简称 FDA)情况简介

FDA是美联邦政府卫生部(DEPARTMENT OF HEALTH AND HUMAN SERVICE简称DHHS直译应为卫生及人类服务部,实即卫生部及有关福利事宜)下的直属机构。是对食品及药物等方面制定规范及进行管理的权威性机关。FDA除主要对食品、药物外还包括有生物制品,化妆品及医疗设施等的管理,与农业部(负责肉类、疏菜、水果的管理)、环境保护局(E.P.A)(负责空气、饮水、废弃物、农药、毒品等的管理)分工统管环境中的化学物。它们都是以立法为根据的代表政府的执法机关。 FDA的前身为化学部(DEPARTMENT OF CHEMLSTRY)建于1906年。现有工作人员约8。

Repurposing Loperamide as an Anti-Infection Drug for the Treatment of Intracellular Bacterial Pathogens

Infections caused by intracellular bacterial pathogens are difficult to treat since most antibiotics have low cell permeability and undergo rapid degradation within cells.The rapid development and dissemination of antimicrobial–resistant strains have exacerbated this dilemma.With the increasing knowledge of host–pathogen interactions,especially bacterial strategies for survival and proliferation within host cells,host-directed therapy(HDT)has attracted increased interest and has emerged as a promising antiinfection method for treating intracellular infection.Herein,we applied a cell-based screening approach to a US Food and Drug Administration(FDA)-approved drug library to identify compounds that can inhibit the intracellular replication of Salmonella Typhimurium(S.Typhimurium).This screening allowed us to identify the antidiarrheal agent loperamide(LPD)as a potent inhibitor of S.Typhimurium intracellular proliferation.LPD treatment of infected cells markedly promoted the host autophagic response and lysosomal activity.A mechanistic study revealed that the increase in host autophagy and elimination of intracellular bacteria were dependent on the high expression of glycoprotein nonmetastatic melanoma protein B(GPNMB)induced by LPD.In addition,LPD treatment effectively protected against S.Typhimurium infection in Galleria mellonella and mouse models.Thus,our study suggested that LPD may be useful for the treatment of diseases caused by intracellular bacterial pathogens.Moreover,LPD may serve as a promising lead compound for the development of anti-infection drugs based on the HDT strategy.

Sulfuryl Group-Involved Drugs Approved by the Food and Drug Administration(FDA)from 2021 to 2023

Organic sulfone compounds,exhibiting interesting bioactivities,were widely applied in the field of pharmaceutical and medicine.And numerous of sulfuryl group-involved drugs were approved by the Food and Drug Administration(FDA).Odevixibat,maralixibat chloride and belzutifan approved in 2021 could be applied in the treatment of progressive familial intrahepatic cholestasis(PFIC),cholestatic pruritus and clear cell renal cell carcinoma(ccRCC),respectively.In 2022,abrocitinib,pyrukynd and voquezna were approved for the treatment of atopic dermatitis,pyruvate kinase deficiency(PKD)and acid-related disorders,respectively.Defencath for preventing bloodstream infections,sparsentan for treatment of proteinuria related to IgA nephropathy,and xacduro for treatment of hospital-acquired bacterial pneumonia(HABP)were approved in 2023.In this review,the synthesis and therapies of these sulfuryl group-involved drugs approved from 2021 to 2023 are discussed in details.

Modes of failure with fractional flow reserve guidewires:Insights from the manufacturer and user facility device experience database

BACKGROUND Fractional flow reserve(FFR)measurement is commonly used in the cardiac catheterization laboratory to assess the functional significance of coronary arterial plaques.Robust real-world data on complications and modes of failure of FFR guidewires are limited.AIM To characterize these outcomes by analyzing the post-marketing surveillance data from the United States Food and Drug Administration Manufacturer and User Facility Device Experience(MAUDE)database for commonly used FFR guidewires.METHODS The MAUDE database was queried from January 2010 through April 2020 for 3 FFR guidewires[PressureWireTM X(Abbott),CometTM(Boston Scientific),and VerrataTM(Philips)]by searching for the following events:“Injury”,“malfunction”,“death”,and“other”.This yielded 544 reports.After excluding incomplete reports,486 reports were analyzed.RESULTS Guidewire tip fracture was the most commonly reported mode of failure,in 174(35.8%)cases followed by guidewire kinking(n=152,31.3%),communication failure(n=141,29.0%),and shaft fracture(n=67,13.8%).In total,133(27.4%)device failures resulted in patient adverse events.The most common adverse event was retained guidewire tip,in 71(53.4%)cases,followed by freshly deployed stent dislodgment(n=26,19.6%)and coronary artery dissection(n=23,17.3%).Seven deaths were reported.CONCLUSION FFR guidewire failures can occur because of various mechanisms and cause patient adverse events.The MAUDE database serves as an important platform for improved collaboration among clinicians,device manufacturers,and regulators to improve device performance and optimize patient outcomes.Our analysis provides mechanistic insights of FFR guidewire failure and associated adverse events but cannot verify causality or provide a comparison among different guidewires.

Anti-obesity drugs currently used and new compounds in clinical development

Obesity is a chronic disease which requires treatment. As lifestyle interventions alone hardly ever result in long-term weight loss, pharmacotherapy is an impor-tant adjunct to lifestyle measures to improve the induc-tion and maintenance of weight loss. Owing to the lim-ited options currently available for the pharmacological treatment of obesity, it is imperative to develop new safe compounds. This study aims to review the current medications approved by European Medicines Agency and United States Food and Drug Administration （FDA） for the treatment of obesity, focusing essentially on their benefits and risks, as well as on the new drugs which are presently under clinical trials. Moreover, it lists the anti-obesity agents that have been recently withdrawn from the market. A revision of the scientifc literature was carried out, through a search on Pubmedfor papers published from January 2010 to January2013. Orlistat （Xenical？） is currently the only long-termpharmacotherapy for obesity available in the Europeanmarket, as rimonabant and sibutramine were with-drawn in 2008 and 2010, respectively, due to serious psychiatric and cardiovascular adverse effects. Lorca-serin （Belviq？） and the association of phentermine and topiramate （QsymiaTM） were recently approved by FDA. Orlistat suppresses appetite inhibiting gastrointestinal lipase, being its adverse effects mostly gastrointestinal. Lorcaserin activates 5-HT2C receptors, phentermine is a norepinephrine releasing drug, and topiramate is an anticonvulsivant drug with weight loss properties.

Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injury Issued by China Food and Drug Administration

1. Introduction Drug-induced liver injury (DILI), defined as liver injury caused by a drug and/or its metabolites, is a common clinical adverse drug reaction1–4. This type of injury can cause acute liver failure and even death in severe cases5.

Status quo of resource allocation of Chinese grass-roots food and drug administrations: from 2011 to 2016

County grass-root food and drug administrations （CGFDA） undertake the front-line supervision of food and drug safety, whose resource allocation is vital to the regulation efficiency and performance. In this article, we aimed to analyze the status quo of resource allocation of CGFDA from the aspects of regulatory organization, staff, funding and equipment using official panel data from 2011 to 2016. The results illustrated that the total amount of regulatory resources of CGFDA was increased annuall y, reaching a rather large scale. However, many problems still existed in its allocation. Therefore, a series of measures should be taken to optimize the resource allocation of CGFDA, such as improving the network of institutional CGFDA, increasing the recruitment requirements on educational level and major, reallocating the structure of resources and guaranteeing the resource demand in less-developed areas.

Analysis of the adverse reactions of atezolizumab: A real-world study based on FAERS database

Objective In this study,we aimed to determine the incidence of adverse drug reactions(ADRs)of atezolizumab,identify ADR signals that are significantly related to atezolizumab,and provide a reference for the rational use of atezolizumab in the clinic through the statistical analysis of its adverse drug events(ADEs)reported in the American Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database.Methods In total,4796 cases of atezolizumab ADEs reported in the American FAERS database from 2017 to 2019 were retrospectively analyzed.Results The top three ADEs were febrile neutropenia(3.7%),anemia(2.9%),and acute renal failure(2.3%).In addition,the incidence rates of some ADEs were significantly different according to sex and age.The systematic organ classification of atezolizumab ADEs involved 32 systems,among which the top three were blood and lymphatic system disorders(585 cases,12.2%),gastrointestinal disorders(433 cases,9.0%),and infections and infestations(401 cases,8.4%).The reporting odds ratio(ROR)method was used to detect the ADR signals of atezolizumab.The ROR(95%confidence interval)of the top ADE,febrile neutropenia,was 39.236(33.757–45.604).In addition,we found 121 cases of complications associated with immune-related ADEs.Conclusion The ADRs of atezolizumab reported in the FAERS database were consistent with those mentioned in the instructions for atezolizumab use,suggesting that atezolizumab has an acceptable and controllable drug effect.

Microbiological Quality of Freshly Prepared, Packaged Fruit and Milk Juices Sold in Cafés, Shops, and Supermarkets in Hargeisa, Somaliland

Background: Due to their delicious taste, high nutritional content, and health benefits, fruit juices are well-known drinks in many countries and are now an essential component of the modern diet. Objective: Determining the microbiological quality of both packaged and freshly made fruit and milk juices. Method: The spread-plate approach was employed to isolate and count the bacteria. 90 ml of sterile peptone water were blended with 10 ml of well-mixed, packed, and freshly made fruit juices. The samples were sequentially diluted (101 - 105) in accordance with the Indian Manual of Food Microbiological Testing Methods. Results: From eight samples of imported packaged fruit and milk juice, the average of total coliform, staphylococci, and viable bacterial counts were zero, 1.39 × 102, and 2 × 102 CFU/ml, respectively. In contrast, from three samples of locally produced fruit and milk juice, the average of total coliform, staphylococci, and viable bacterial counts were zero, 5.83 × 102, and 2.73 × 103 CFU/ml, respectively. Four samples of handmade prepared fruit and milk juices had a mean of total coliform, staphylococci, and viable bacterial count of 1.441 × 104, 4.1 × 103, and 2.35 × 105 CFU/ml, respectively. Conclusion: 33.3% of the results from microbiological analysis of freshly made fruit and milk juices met the permissible range of the Revised Microbiological Standards for Fruit and Vegetables and Their Products, which were published in 2018 and as well as the Hong Kong Center for Food Safety, whereas 66.7% of the microbiological analyses of freshly prepared fruit and milk juices were above the permissible reference range of GSO standard 2000. 12.5% of the investigated imported and packed fruits and milk juices had one failed test (TSC), which was above the acceptable limit, 87.5% of the tested samples of fruit and milk juices fulfilled the necessary standards of TCC, TVBC, and TSC. 100% of the tested locally manufactured fruit and milk juices complied with TSC, TCC, and TVBC requirements. All investigations showed that freshly made fruit and milk juices were heavily contaminated (Total viable bacterial count, total coliform count, and total staphylococcus count). .

美国FDA致幻药临床研究考虑要点的行业指导原则草案介绍

目的:促进我国对致幻药精神心理疾病治疗应用的开发、研究和监管。方法:在美国食品药品管理局(FDA)网站,查寻新近发布的相关指导原则并详细而具体地介绍该指导原则。结果与结论:展示了FDA于2023年6月发布的“致幻药临床研究考虑要点的行业指导原则草案”的具体内容,为开发用于治疗精神心理疾病(例如精神障碍、物质使用障碍)的致幻药提出了一些临床研究的一般考虑因素,以确保符合伦理要求以及试验完整性和结果可靠性。指导原则按专业领域分别讨论了致幻药与临床研究相关的化学、生产和控制;非临床试验;临床药理学;滥用可能性评估和临床试验方面面临的特殊问题。该指导原则对我国开展这方面的工作具有重要参考价值。

基于FAERS数据库分析波生坦药物不良事件

目的:基于美国食品药品监督管理局不良事件报告系统(FAERS),挖掘波生坦不良事件信号,判断其安全性,以期临床安全用药提供参考。方法:选取FAERS数据库2016年1季度~2022年2季度数据信息,比照MedDRA不良事件编码处理数据,提取以波生坦为首要怀疑药品的不良事件报告,采取比例报告比值法(PRR)和报告比值法(ROR)对信号进行分析。结果:以波生坦为首要怀疑药品的不良事件报告中,女性占比(61.51%)高于男性(21.40%);通过对器官系统分类(SOC)分析发现波生坦产生不良反应主要集中在全身性疾病及给药部位各种反应、呼吸系统、胸及纵隔疾病、感染及侵染类疾病;对首选语(PT)分析发现呼吸困难、死亡、感染性肺炎的发生排在前3位;对低位语(LLT)分析发现波生坦易导致死亡、基因突变、肺水肿等不良事件的发生。结论:通过对FAERS数据库中波生坦不良反应的挖掘,从SOC、PT、LLT 3个层次分析了不良事件特点,为波生坦在临床中的安全使用提供了参考依据。

基于OpenFDA数据库的沙库巴曲缬沙坦不良事件报告信号挖掘与分析

目的促进临床安全使用沙库巴曲缬沙坦。方法检索美国食品和药物管理局公共数据开放项目(OpenFDA)2015年7月7日至2023年8月2日沙库巴曲缬沙坦药品不良事件(ADE)报告,采用报告比值比(ROR)法进行风险信号挖掘,并以监管活动医学词典的系统器官分类(SOC)法进行统计与分析。结果共检索到相关ADE报告97574例,发生群体男性较多;老年患者发生比例较高;上报国家以美国最多;一般和严重ADE分别占51.55%和48.45%;明确记录转归情况的报告中,25.68%的患者出现死亡,23.11%的患者未恢复。共挖掘出70个阳性信号,涉及15个SOC,全身性疾病及给药部位各种反应的信号数量最多(16个),精神疾病、耳及迷路疾病2个SOC及31个风险信号未被药品说明书收录。结论沙库巴曲缬沙坦常见ADE信号与药品说明书基本一致,但还应关注药品说明书中未收录的风险,如肺水肿、胸痛、胸部不适,射血分数下降等,以进一步保证患者的用药安全。

阿奇霉素注射剂中潜在N-亚硝胺的测定与风险分析

目的探讨阿奇霉素注射剂中潜在N-亚硝胺的测定与风险。方法根据枣庄市食品药品检验检测中心依据美国食品药品管理局(FDA)、欧盟简介及欧洲药物管理局(EMA)所发行的相关指南,结合降解实验分析阿奇霉素结构及特点,并识别N-亚硝胺风险,明确控制限度,构建高效液相色谱串联质谱(HPLC-MS/MS),对阿奇霉素注射剂中的潜在N-亚硝胺实施测定。结果准确度:向供试品(批号:191013)中加入适量溶液,配置成为不同浓度(50%、100%、150%)水平的定限量(LOQ)溶液,回收率为85.9%~101.8%,平均回收率(n=12)为94.2%,回收率相对标准偏差(RSD)为5.4%。结论市面上阿奇霉素注射剂中的N-亚硝基二甲胺(NDMA)风险具有可控性,通过HPLC-MS/MS法检测可满足灵敏度的限定要求,且专属性回收率具有良好的回收度,便于各级质量检测机构对阿奇霉素中的NDMA风险作出精准评估,以此来强化质量,控制风险措施,同时也为监测化学合成药物中潜在N-亚硝胺的风险评估提供有效的鉴别基础。

基于FAERS的索托拉西布不良事件信号挖掘分析

目的 研究旨在挖掘索托拉西布不良事件(AE)风险,提供临床安全参考。方法 从美国食品药品监督管理局的AE报告系统数据库中收集2021年第一季度至2023年第二季度的索托拉西布AE报告,使用报告比值比法挖掘风险信号。结果 共提取6553918例AE报告,主要怀疑药物为索托拉西布的有1599例。常见AE包括腹泻、死亡、疾病进展、疲劳、恶心、肝毒性、肝功能检测结果升高等。可能新的AE风险信号包括便秘、肺栓塞、嗜睡、脑血管意外等。结论 索托拉西布的临床使用需加强监测,确保患者用药安全,尤其要关注便秘、肺栓塞、嗜睡、脑血管意外等情况。

1984～2014年治疗性生物药物发展历程及展望

为了全面系统了解1984-2014年全球生物药物的发展历程,掌握30年来生物药物的发展脉络、上市药物特点、研发管线布局等信息,该文以Drugs＠FDA、中国食品药品监督管理总局数据库、PubMed、Embase.com、ClinicalTrail.Gov等数据库为数据来源,系统采集国内外上市和在研的生物药物信息.对已经上市和在研的生物药物从创新程度、药物适应症分布、药物化学特性、药物研发阶段等方面进行了深入分析.结果表明全球生物药物在1996年以后开始快速发展,2001～2005年是生物药物成果最为显著的阶段.肿瘤、免疫系统疾病、内分泌和代谢疾病、血液系统疾病、骨骼肌系统疾病是生物药物研究的重点领域,上市药物较多.目前抗体已经发展成为治疗性生物药物的主宰药物,在肿瘤、消化、免疫、呼吸、泌尿、骨骼肌疾病、疾病诊断等不同领域广泛应用.

我国法定中药注射剂概况

目的:了解我国现行的法定中药注射剂概况。方法:通过国家食品药品监督管理局网站、药品说明书以及相关材料统计中药注射剂的药品种类、规格、剂型、批准文号、处方组成等情况,并进行分析统计。结果:我国现行的法定中药注射剂共有130种、1290个批准文号,药品剂型以小容量注射液为主。同种药品有多个批准文号和生产厂家的现象比较普遍,单个品种最多有8个规格、182个批准文号、115个生产厂家。结论:我国现行的法定中药注射剂在注册、审批、质量标准等方面仍存在不足,开展中药注射剂的安全性再评价工作十分重要。

美国食品添加剂的安全监管及其启示

食品添加剂在食品行业中占有重要地位,它的使用直接关系着食品的性能与安全,因而食品添加剂安全监管体制在整个社会法制体系中占有重要的地位。美国联邦食品、药品和化妆品法规定,只有经过美国食品药品监督管理局评价和公布的食品添加剂才能生产和在食品中使用。本文综述了美国食品添加剂的法律法规及监管体系。美国十分重视对食品添加剂的法律法规体系建设,并形成了严格、规范、有效的监管,其中有些经验对我国完善食品添加剂管理法规和监管体系具有重要的借鉴意义。

对保健食品的现状分析及监管探讨

保健食品是我国传统食疗文化的继承和发展,目前已有了长足发展,并且已经成为具有相当规范的产业,但存在诸多问题,使保健食品处于严重的信任危机。本文通过对中国保健食品发展、存在问题、监管体制等现状分析,提出监管对策。