The Problems of the Safety Evaluation of Biotechnology Derived Drugs

Recent years have witnessed rapid advances in the toxicologic assessment of biotechproducts.Safety assessment of a biotech product is a complex and multiple process.This includes a knowledge of its pharmaco-biological characteristics,and identifyingthe target patient population and the proposed clinical application. To make a decision on the safe human application(the products are administering tohumans for therapeutic purposes),besides the identity and purity of the final product,

Drug utilization evaluation of medications used in the management of neurological disorders

Background and object:The burden of neurological disorders in India is expected to increase due to the rapid demographic and epidemiological transition,with irrational drug use,which is also a global concern.Thus,drug utilization evaluation is designed to ensure appropriate medicine use within the healthcare settings.The aim of the study was to assess the rate and pattern of drug utilization in the management of neurological disorders.Materials and methods:A hospital-based cross-sectional drug utilization evaluation study on neurological drugs was carried out at the Department of Neurology over a span of six months.All legible prescriptions consisting neurological medications irrespective of patient's gender,aged≥18 years were included for the study.The World Health Organization(WHO)core drug use indicators were used to assess the drug prescribing and utilization patterns.Results:A total of 310 prescriptions were reviewed,where male predominance was found to be 56.45%.Out of 310 prescriptions,drugs belonging to 26 neurological classes were prescribed for the management of various neurological disorders.The majority of patients were diagnosed with epilepsy and the most prescribed drugs per patient were phenytoin(14.8%)and valproic acid(6.45%).By following the WHO core drug prescribing indicators,65.47%of drugs prescribed from the India National List of Essential Medicines,2022,followed by 29.83%of drugs prescribed in generic name and 10.86%of prescriptions including injections.Conclusion:The study findings showed that the prescribing pattern in the Department of Neurology was in accordance with the WHO core prescribing indicators.But,the extent of polypharmacy prescriptions was very high.Therefore,interventions are very necessary to promote rational drug prescribing patterns and thus clinical pharmacists can contribute to assess and review the drug utilization pattern to optimize the drug therapy and improvement in patient safety.

Clinical Observation and Safety Evaluation of Zhuang Medicine Xiaoyan Zhiyang Formula for Dermatosis

[Objectives]To observe the clinical efficacy and safety of Zhuang Medicine Xiaoyan Zhiyang Formula by retrospective analysis of clinical use.[Methods]A total of 225 cases were collected,including 117 males and 108 females,115 cases of contact dermatitis and 110 cases of acute eczema.Zhuang Medicine Xiaoyan Zhiyang Formula was administered to 225 patients with contact dermatitis and acute eczema and the clinical efficacy was evaluated.[Results]After one week of treatment,among 225 patients with contact dermatitis and acute eczema,76 cases were cured(33.78%),133 cases showed marked response(59.11%),16 cases(7.11%)were improved,0 case was ineffective,and the overall response rate was 92.89%.After one week of Zhuang Medicine Xiaoyan Zhiyang Formula treatment,the symptoms of itching,pain and swelling were significantly improved in all patients,and the rash was partially crusted without new symptom,and there were no complications and adverse reactions.[Conclusions]Zhuang Medicine Xiaoyan Zhiyang Formula therapy has a remarkable effect in the treatment of contact dermatitis and acute eczema.

The Anticancer Potential of Quassinoids-A Mini-Review

The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature.Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes,several quassinoids have exhibited synergistic effects with anticancer drugs.This article provides an overview of the potential anticancer properties of quassinoids,including their cytotoxic and antitumor activities,mechanisms of action,safety evaluation,and potential benefits in combination with anticancer drugs.

Evaluation of the safety and efficiency of cytotoxic T cell therapy sensitized by tumor antigens original from T-ALL-iPSC in vivo

Background:Since RNA sequencing has shown that induced pluripotent stem cells(iPSCs)share a common antigen profile with tumor cells,cancer vaccines that focus on iPSCs have made promising progress in recent years.Previously,we showed that iPSCs derived from leukemic cells of patients with primary T cell acute lymphoblastic leukemia(T-ALL)have a gene expression profile similar to that of T-ALL cell lines.Methods:Mice with T-ALL were treated with dendritic and T(DC-T)cells loaded with intact and complete antigens from T-ALL-derived iPSCs(T-ALL-iPSCs).We evaluated the safety and antitumor efficiency of autologous tumor-derived iPSC antigens by flow cytometry,cytokine release assay,acute toxicity experiments,long-term toxicity experiments,and other methods.Results:Our results indicate that complete tumor antigens from T-ALL-iPSCs could inhibit the growth of inoculated tumors in immunocompromised mice without causing acute and long-term toxicity.Conclusion:T-ALL-iPSC-based treatment is safe and can be used as a potential strategy for leukemia immunotherapy.

Comparative Evaluation of Antitumor Chinese Patent Medicine Injections Based on Evidence-Based Medicine and Markov Model

Objective: The objective of this study was to explore the safety, efficacy, economy, and other aspects of frequently-used antitumor Chinese patent medicine injections through a comprehensive evaluation of evidence-based medical research to provide scientific information and decision-making basis for drug selection, rational drug use, public awareness of safe drug use, and medical insurance. Materials and Methods: The names of five frequently used antitumor Chinese patent medicine injections were used as search terms, including the compound Sophora flavescens injection, Kangai injection, Aidi injection, Kanglaite injection, and Brucea javanica oil emulsion injection. Relevant evidence-based medical research was extracted from the databases. A descriptive evaluation was conducted, and the Markov model was used for the cost-benefit analysis. Finally, the above injections are ranked by comprehensive scores using the multi-criteria decision analysis and Delphi method. Results: The five injections had their own advantages in enhancing the effectiveness of anti-tumor treatments, improving the quality of life for cancer patients, and reducing the incidence of adverse reactions. From the perspective of economy and other attributes, compound S. flavescens was superior to B. javanica oil, Aidi, Kangai, and Kanglaite. After a comprehensive evaluation of the above five injections, the compound S. flavescens injection received the highest score. Conclusions: Compound S. flavescens, Kangai, Aidi, B. javanica oil, and Kanglaite have their own advantages in effectiveness and no significant difference in safety. Compound S. flavescens injection has the highest comprehensive score. Clinical attention should be paid to monitoring the initial stage of medication and special groups.

Effects of two novel sugar drug candidates on CYP450 isoforms in different sexed Chinese human liver microsome in vitro

The sex-based differences between the effects of two novel sugar-based drug candidates,a sulfated polymannuroguluronate(SPMG-911)and an acidic oligosaccharide sugar chain compound(AOSC-971),on the enzymes CYP 1A2,CYP2E1 and CYP3A4 of Chinese human liver microsome were investigated.The results showed that neither SPMG-911 nor AOSC-971 have any effect on CYP3A4,AOSC-971 induced the CYP 2E1 in men but have no effect on CYP1A2,SPMG-911 inhibit the CYP1A2 also in men but have no effect on CYP2E1.The results are useful for their safety evaluation,as well as for the prediction of inter-drug interactions associated with the two drugs.

放射性药品的药物警戒

放射性药品在医疗领域发挥着重要作用,但同时也存在一定的风险和安全隐患。医疗机构实行药物警戒,保障患者用药安全,包括放射性药品的药物使用安全。美国和欧盟药物警戒体系的运行及管理等方面较为成熟,中国可以借鉴其先进理念,建立适合自己的放射性药物警戒体系。

Regulatory evaluation of efficacy and safety of new drugs in China

Accessibility, availability, and rational use of medicines are widely recognized priorities for guaranteeing equity in health care. Commercial pressure can twist health policy if pharmaceutical companies are allowed to promote and impose their products beyond clear public-health interest. National regulatory

Barnesiella intestinihominis菌的安全性评价

目的:对分离自健康成人粪便中且在代谢性疾病发生状态下生长可能受到抑制的Barnesiella(巴恩斯氏菌属)厌氧菌进行体内外生物安全性评价,为今后代谢性疾病的微生态制剂的研发与应用提供基础。方法:通过急性毒性试验,连续14 d给昆明鼠灌胃不同剂量的Barnesiella intestinihominis(B.intestinihominis)菌培养液,观察动物是否出现死亡、中毒现象以及观察体重、生化指标的变化进行体内安全性评价。通过溶血性实验,胃酸和肠液的耐受性实验,以及其对9种抗生素的敏感性实验来进行体外评价。结果:实验组均未出现B.intestinihominis菌灌胃导致的死亡,中毒现象,其体重和脏器指数同对照组相比差异无统计学意义(P>0.05),各脏器也未出现任何病理学变化。B.intestinihominis菌在哥伦比亚血琼脂平板上不产生溶血环,属于γ溶血;其胃酸耐受性不强,但肠液耐受性良好,对氯霉素、氨苄西林、万古霉素和四环素敏感,但是对链霉素、红霉素、卡那霉素、庆大霉素、克林霉素耐药。结论:口服B.intestinihominis菌株对小鼠无毒性作用,具有良好的体内安全性,其胃酸耐受性不强,对革兰阴性菌有作用的抗生素敏感,若作为微生态制剂还需要验证对不同疾病的有益效果以及需要制作保护剂。

肾脏类器官的研究进展及其在药物安全性评价中的应用

肾毒性是导致药物研发失败的原因之一,所以建立确定可靠的方法评价药物肾毒性是当前药物安全性评价急需解决的问题。最近,一种新型体外研究模型—类器官备受关注,可高度模拟体内组织、器官的功能结构,具有稳定的遗传特征。由于肾脏类器官具备真实器官结构和功能,在药物肾毒性评价的研究中极具应用价值和发展潜力。因此,本文将对肾脏类器官的构建及其在药物安全性评价中的应用进行归纳总结,以期为肾脏类器官的药物毒性评估提供相关理论依据,帮助筛选相关药物的潜在不良反应。

替雷利珠单抗免疫相关不良事件研究进展

目的为临床安全使用替雷利珠单抗提供参考。方法检索中国知网、维普、万方、中国生物医学文献数据库及PubMed,Embase,Web of Science等数据库(检索时限自建库起至2023年4月30日),对替雷利珠单抗安全性的相关临床研究、上市后不良反应的个案报道等30多篇文献进行系统整理,总结替雷利珠单抗免疫相关不良事件(irAE)的发生特点。结果不同的临床试验中,替雷利珠单抗irAE总发生率为22.2%~76.7%;其中≥3级irAE的发生率为7.0%~36.7%。替雷利珠单抗相关irAE常发生于皮肤系统、内分泌系统、消化系统、泌尿系统、呼吸系统、心血管系统,临床表现为皮疹,甲状腺功能异常、高血糖,腹泻,肾功能损伤,肺炎,心肌病等。基于目前的临床观察及相关研究,替雷利珠单抗irAE程度大多轻微,未导致治疗中断。结论irAE发生情况显示,替雷利珠单抗用于临床恶性肿瘤的抗肿瘤治疗有一定安全性,但作为新上市的药物,临床应用时间短,经验相对不足,建议临床医师严格把握适应证,做好用药监护,以确保用药安全。

吸入用乙酰半胱氨酸溶液自研药非临床安全性评价

目的为吸入用乙酰半胱氨酸溶液自研药的临床安全使用提供依据。方法取18只雄性日本大耳白兔,按体质量分层随机化分组法分为阴性对照组(等体积0.9%氯化钠注射液)、上市品对照组(原研药0.1 mg/mL)和给药组(自研药0.1 mg/mL),各6只。雾化吸入给药35 mg/kg,给药体积均为0.35 mL/kg,各组均给予相应药物,每日上午、下午各1次,连续14 d。记录呼吸道刺激性症状发生及恢复时间。分别于末次给药24 h及14 d后,各组取3只兔处死并解剖,肉眼观察刺激反应,采用苏木素-伊红染色,观察病理形态。取30只Hartley豚鼠,按体质量分层随机化分组法分为阴性对照组(0.9%氯化钠注射液0.8 mL/d)、阳性对照组(0.9%氯化钠注射液0.8 mL/d)、上市品对照组[原研药80 mg/d(0.8 mL/d)]及低剂量组[自研药40 mg/d(0.4 mL/d)]和高剂量组[自研药80 mg/d(0.8 mL/d)],各6只,各组动物隔日致敏(10%卵白蛋白溶液0.6 mL/d)1次,共3次。分别于末次致敏14 d及21 d后,各组取3只豚鼠,按2倍致敏剂量进行激发。根据过敏反应发生率和发生程度综合评价主动全身过敏反应发生情况。结果各组兔的外观、行为、粪便等均正常,给药后无咳嗽等症状;大体解剖均未见明显异常;与阴性对照组和上市品对照组比较,给药组未见药物延迟或蓄积作用。各组豚鼠未出现与给药相关的异常症状,过敏反应均为阴性。结论吸入用乙酰半胱氨酸溶液自研药对日本大耳白兔无明显呼吸道刺激作用,对豚鼠无明显的全身致敏作用。

药物临床试验中不良事件管理问题分析

目的分析药物临床试验中不良事件管理问题,提高临床试验的质量和水平。方法收集某医院临床试验机构21项临床试验项目质控报告,依据《药物临床试验数据现场核查要点》,对其中有关不良事件管理方面存在的问题进行统计分析。结果21个项目中发现不良事件管理相关问题197次,其中收集起点与试验方案是否一致方面的问题17次(占8.6%);未跟踪随访到终点方面26次(占13.2%);不良事件名称记录不规范方面58次(占29.4%);不良事件漏记方面49次(占24.9%);异常有无临床意义判定不合理方面34次(占17.3%);与试验药物相关性判定不合理方面13次(占6.6%)。结论不良事件的记录与评价方面存在问题较多,需临床试验机构及研究者在临床试验开展过程中重点关注。

集采常态化背景下仿制药质量安全应急管理能力评估指标体系构建

目的 构建我国仿制药质量安全应急管理能力评估指标体系,为评估并提高集采常态化背景下仿制药质量安全应急管理能力提供参考。方法 基于理论研究和文献分析初步拟定仿制药质量安全应急管理能力评估指标体系,采用德尔菲法和层次分析法确定评价指标体系并计算权重。结果 两轮咨询专家积极程度、权威系数与意见协调程度较好,最终构建了仿制药质量安全应急管理能力评估指标体系,包括一级指标4个(质量风险监测预警能力、应急准备能力、响应处置能力与应急恢复能力)、二级指标11个(如仿制药研发与生产过程质量风险监测预警能力、应急组织机制保障能力、应急响应处置能力等)、三级指标75个(如仿制药原料质量风险监测、仿制药质量和疗效一致性评价、仿制药利润空间风险隐患监测等)。其中,一级指标中质量风险监测预警能力的权重最大(0.392 4),二级指标中仿制药研发与生产过程质量风险监测预警能力的组合权重最大(0.146 0),三级指标中仿制药原料质量风险监测的组合权重最大(0.023 0)。结论 本研究构建的仿制药质量安全应急管理能力评估指标体系层次分明、权重合理,具有一定的可信度,可作为集采常态化背景下仿制药质量安全应急能力评估管理与决策的有效工具。

安全性视角下基本药物制度评价模型构建及效果评价

目的构建安全性视角下基本药物制度评价模型,为基本药物安全性管理提供参考。方法通过德尔菲法和层次分析法确定各级指标和权重,构建安全性评价模型。利用中国上市药品目录集、《中国药典》等收集基本药物(2018年)安全性指标数据。运用李克特量表法对实证数据进行评分,将评分值输入构建的模型中,获得安全性视角下基本药物制度的效果评价分值。结果构建模型的5个一级指标(准则层)的权重分别为0.261,0.189,0.431,0.075,0.083,10个二级指标(指标层)的权重分别为0.504,0.496,0.433,0.567,0.429,0.571,1.000,0.252,0.551,0.196。运用该模型对基本药物进行实证评估,综合评价总得分为3.684分,综合评价为73.68%。结论构建的模型稳定可靠、具有可行性,能全面反映基本药物的安全性,现行基本药物的安全管理需进一步完善。

信息化闭环管理模式对医院药品安全管理质量的提升评价

医院药品安全管理质量是保障患者用药安全的重要环节,需要医院全体员工的共同努力和高度重视,药品管理要求严格、记录烦琐,缺乏信息化手段会耗费较多时间和人力,监管困难,造成浪费和安全隐患,管理不善可能导致严重后果。因此,在医院药品安全管理中实施有效的管理干预十分重要。实施信息化闭环管理模式对医院药品安全管理质量有着积极的促进作用,有助于提升医院药品管理的水平和质量,保障患者用药安全。

我国药品和医疗器械关联审评审批制度对化妆品原料管理和产品安全评价的启示

目的:研究我国药品、医疗器械关联审评审批相关制度,为化妆品原料管理和产品安全评价提供参考。方法:对近年来国家药品监督管理部门发布的药品、医疗器械关联审评审批政策进行梳理总结,对相关监管要求和技术管理手段进行分析,并与化妆品监管要求和管理现状进行对比。结果与结论:在考虑行业差异和监管差异的基础之上,可参考借鉴我国药品和医疗器械关联审评审批相关制度和配套措施,优化我国化妆品审评审批流程、划清安全责任界限、加强原料信息管理、借助信息化支撑手段,探索“化妆品原料安全信息库”的科学应用,提高化妆品原料管理和产品安全评价的整体效率。

尿通卡克乃其片临床使用安全性评价

目的探讨尿通卡克乃其片临床使用安全性。方法检索国内外数据库自建库起至2022年9月尿通卡克乃其片相关不良反应的文献。运用医渡云系统回顾性检索新疆维吾尔自治区人民医院2018年1月至2022年9月使用尿通卡克乃其片的出院患者,对尿通卡克乃其片相关不良反应、器官损害、严重程度及患者转归进行分析。结果共检索出涉及尿通卡克乃其片药品不良事件文献11篇,大多数文献报道患者服用尿通卡克乃其片治疗前后实验室检查未见异常,无严重不良反应报道。本院发现尿通卡克乃其片相关不良反应患者81例,以男性、年龄41~79岁、汉族和维吾尔族、体重指数>18~30 kg/m^(2)、无药物过敏史患者多见。81例尿通卡克乃其片相关不良反应患者中,最常见的累及器官损害为胃肠道损害,其次为皮肤及附件损害;合并用药1、2、3、>3种患者分别为27例(33.3%)、14例(17.3%)、5例(6.2%)、21例(25.9%);用药后12、24、48、72、≥96 h发生不良反应患者分别为2例(2.5%)、39例(48.1%)、24例(29.6%)、11例(13.6%)、2例(2.5%)。81例患者不良反应严重程度均为一般,不良反应治愈51例(63.0%)、好转27例(33.3%)、不详3例(3.7%)。结论尿通卡克乃其片安全性良好,但临床用药期间仍应加强患者各项实验室指标监测,保障患者用药安全。

米非司酮超药品说明书用药循证评价

目的为米非司酮超药品说明书用药提供循证依据。方法检索PubMed、Embase、The Cochrane Library、中国知网、维普和万方数据库,检索时限为各数据库自建库起至2023年3月。筛选米非司酮治疗异位妊娠、稽留流产及围绝经期功能失调性子宫出血的系统评价/Meta分析,采用AMSTAR 2量表对纳入文献进行方法学质量评估,并依据GRADE分级对结局指标进行证据质量等级评价。结果共纳入7篇系统评价/Meta分析,其中英文文献1篇,中文文献6篇。方法学质量,低质量1篇,极低质量6篇;结局指标证据质量,中级3个,低级10个,极低级7个。7篇文献中,2篇报道了有利于异位妊娠患者治疗成功率升高,其中1篇还报道了有利于患者持续性异位妊娠发生率降低;1篇报道了有利于稽留流产患者完全流产率升高,二次清宫率降低;4篇报道了有利于围绝经期功能失调性子宫出血患者围绝经期功能性子宫出血症状和体征改善,其中1篇还报道了米非司酮高剂量(12.5 mg/d)的总有效率优于低剂量(6.5 mg/d)。结论米非司酮治疗异位妊娠、稽留流产及围绝经期功能失调性子宫出血的循证依据尚不充分,可能存在潜在的用药安全风险,仍需补充更多的高质量研究进一步考察。