实施《医疗器械生产质量管理规范》加强对初包装材料的管理

目的 保证医疗器械包装材料的质量能够满足医疗器械的要求.方法 结合《直接接触药品的包装材料和容器管理办法》对药品包装材料产品注册、生产洁净度以及注册品种等管理要求展开讨论.结果与结论 提出加强医疗器械初包装材料选择和生产管理方面的合理化建议.     

美国药品生产科学及对我国药品生产质量管理的启示

目的:为我国药品生产质量管理的改进提供借鉴。方法:收集文献,追踪美国药品生产科学的最新知识,分析我国《药品生产质量管理规范》(GMP)存在的问题,并提出建议。结果与结论:质量的提高和改进总是伴随着生产过程的,质量改进是全面质量管理的精髓。我国须制定更合理、科学的GMP,形成更开放的质量体系并且重视药品的生产过程。     

Novel investigational agents for the treatment of scleroderma

Introduction: The purpose of this article is to highlight novel therapies that are being used in scleroderma (SSc). Therapeutic interventions in SSc generally target at least one of three ongoing biological processes characteristic of the disease: vasculopathy, autoimmunity and tissue fibrosis. Treatment decisions in SSc are determined by the level of disease activity and the degree of specific organ involvement. Traditional therapy has primarily focused on organ-specific management without clear evidence of overall disease modification.

Areas covered: The authors provide a review of a variety of agents, which are already used for other autoimmune diseases, that are now being used to treat active SSc skin or lung disease, including rituximab, tocilizumab and IVIG. Several agents studied in vitro and in animal models of fibrosis have shown promise, including bortezomib, LPA-1 antagonists, anti-CCN2 therapy, anti-IL-13 and thrombin antagonists. The authors also provide details on targeting intracellular molecular pathways and matricellular proteins, which is another novel area of investigation.

Expert opinion: Combination therapy may be necessary to control the complex biological network active in SSc. Most of the current evidence that suggest benefit of these agents is based on small population studies. Ultimately well-designed clinical trials are required to define the role of these agents in treating SSc.     

浅谈医院制剂室持续性实施GPP的方法

目的:持续性实施《医疗机构制剂配制质量管理规范》(GPP),巩固GPP认证成果。方法:介绍我院制剂室GPP认证后加强生产和质量管理的具体做法。结果与结论:通过完善GPP文件系统和促进其实施的制度,健全了生产和质量管理体系,实现了人本管理向文本管理的转变;借助内部微机联网管理加强了生产在线监控和制剂质量管理;员工们对GPP认识的提高,使GPP的各项要求有效地贯彻到制剂生产、管理、保管、发放的全过程、全方面。由此,我院制剂室实现了有效、持续的GPP管理。     

对医疗器械生产质量管理规范试点工作的思考

目的在试点基础上总结经验,推进我国全面实施《医疗器械生产质量管理规范》。方法在对《医疗器械生产质量管理规范》试点情况和结果详细分析的基础上,讨论了试点成效和对今后的启示。结果与结论通过试点,为法规的完善和今后我国全面实施《医疗器械生产质量管理规范》奠定了基础,使其更加符合我国监管实际,切实将医疗器械质量体系管理提升到新水平。     

New investigational antifungal agents for treating invasive fungal infections

Systemic fungal infections have been recognised as a major cause of morbidity and mortality during the last two decades. There are only a few therapeutic options for these infections. Severe toxicity, such as impairment of renal function, limits the use of amphotericin B. Flucytosine is associated with side effects and drug resistance. Fluconazole and itraconazole are safer, though emergence of resistance and innate resistance in some fungal pathogens is a concern in their use. Therefore, there is a need for developing novel drugs and/or treatment strategies to combat these infections. In recent years, increased efforts by the pharmaceutical industry and academia have led to the discovery of new re-engineered or reconsidered antifungal agents that are more efficacious, safer and have a broad spectrum of activity. Lipid formulations of polyene antifungal agents, amphotericin B and nystatin, have the advantage of improved therapeutic index. Activity against resistant fungi, high bioavailability, safety and longer half-life are the properties that encourage development of the newer triazoles (e.g., voriconazole, ravuconazole and posaconazole). Echinocandin-like lipopeptide antibiotics are among the antifungal agents with a novel mode of action. In addition to these lead investigational compounds, development of newer antifungal agents is underway.     

Review article: investigational agents for chronic hepatitis C

Background  The need for effective treatment for chronic hepatitis C infection has driven the development of novel antiviral agents that target specific steps in the viral replication cycle.
Aim  To evaluate the current literature concerning investigational agents for chronic hepatitis C virus infection.
Methods  Resources used included PubMed, conference proceedings from the American and European Liver Associations' meetings 2005–2008 and the National Institute of Health's clinical trials website ( http://www.clinicaltrials.gov ). The focus was restricted to investigational agents that have progressed beyond preclinical development.
Results  Over 50 investigational agents for chronic hepatitis C infection are currently in clinical development. Specifically targeted anti-viral therapy for HCV (STAT-C) shows great promise with NS3/4a protease inhibitors now entering phase 3 programmes. New interferon-α and ribavirin formulations aim to optimize anti-viral efficacy yet limit toxicity. Other candidates include novel immunomodulators and therapeutic vaccines.
Conclusions  A new era of therapy for chronic hepatitis C beckons, promising increased cure rates with shortened duration of therapy. However, the era will not be without challenges including viral resistance, drug toxicity and the need to optimize combination therapy in the face of a rapidly evolving therapeutic arsenal.     

New investigational antifungal agents for treating invasive fungal infections

Systemic fungal infections have been recognised as a major cause of morbidity and mortality during the last two decades. There are only a few therapeutic options for these infections. Severe toxicity, such as impairment of renal function, limits the use of amphotericin B. Flucytosine is associated with side effects and drug resistance. Fluconazole and itraconazole are safer, though emergence of resistance and innate resistance in some fungal pathogens is a concern in their use. Therefore, there is a need for developing novel drugs and/or treatment strategies to combat these infections. In recent years, increased efforts by the pharmaceutical industry and academia have led to the discovery of new re-engineered or reconsidered antifungal agents that are more efficacious, safer and have a broad spectrum of activity. Lipid formulations of polyene antifungal agents, amphotericin B and nystatin, have the advantage of improved therapeutic index. Activity against resistant fungi, high bioavailability, safety and longer half-life are the properties that encourage development of the newer triazoles (e.g., voriconazole, ravuconazole and posaconazole). Echinocandin-like lipopeptide antibiotics are among the antifungal agents with a novel mode of action. In addition to these lead investigational compounds, development of newer antifungal agents is underway.     

从统计数据看FDA海外cGMP检查的实施情况

美国是全球最大的药品消费市场,各国药企都争相进入.任何正式进入美国市场的药品生产企业都须经过FDA的严格检查和监督.本文就FDA对海外制药企业检查的情况进行统计分析,以期对制药企业实施cGMP及应对FDA检查的准备有所借鉴.     

对中国2010版《药品生产质量管理规范》中清洁验证的分析

按照2010版药品生产质量管理规范(GMP)第一百四十三条要求:清洁方法应当经过验证,证实其清洁的效果,以有效防止污染和交叉污染。清洁验证应当综合考虑设备使用情况、所使用的清洁剂和消毒剂、取样方法和位置以及相应的取样回收率、残留物的性质和限度、残留物检验方法的灵敏度等因素。就GMP中相应的条款进行解读分析,以便更好的理解本条款和用最恰当的实施措施满足法规要求,进一步加大降低药品交叉污染的风险。     

浅析现行《药品生产质量管理规范》中存在的问题及对策

目的:为完善我国《药品生产质量管理规范》(GMP)提供参考。方法:结合GMP标准和GMP实施过程中出现的问题,从系统、顾客、供应商、企业负责人和文件等方面进行分析。结果与结论:GMP标准本身存在的问题影响了我国GMP工作的深入实施。为改进和优化GMP标准,建议整合过程系统,使设计质量与生产质量相匹配,构建开放的质量管理体系,强调企业负责人的引领作用,建立层次清晰、通用性强的文件系统。     

Comparative efficacy of new investigational agents against Helicobacter pylori

BACKGROUND: Emergence of antibiotic resistant Helicobacter pylori has necessitated the identification of alternate therapies for the treatment of this infection. AIM: To assess the in vitro efficacy of two investigational agents: DMG-MINO CL 344 (a N,N-dimethylglycylamido derivative of minocycline), and davercin, a cyclic carbonate of erythromycin A as compared to older antibiotics (clarithromcyin, azithromycin, minocycline, tetracycline, ofloxacin, ciprofloxacin, cefixime) against clinical isolates of H. pylori. METHODS: Testing was performed using the agar dilution method approved by the NCCLS subcommittee on antimicrobial susceptibility testing, Helicobacter pylori working group. Under these guidelines, Mueller-Hinton agar containing 5% aged sheep blood was used. All incubations were done under CampyPak Plus conditions for 72 h at 37 degrees C. The drug concentrations in the agar ranged from 0.016 to 16 microg/mL. Twenty-one clarithromycin-resistant and 16 clarithromycin-susceptible clinical isolates of H. pylori obtained from patients with duodenal ulcer were used. H. pylori ATCC 43504 was used as the control in all determinations. RESULTS: Against clarithromycin susceptible isolates, all antimicrobial agents except the fluoroquinolones were highly effective. Against clarithromycin-resistant H. pylori, the MIC50/MIC90 values showed that the tetracyclines and cefixime were the most efficacious agents. The fluoroquinolones and macrolides were ineffective. Macrolide cross-resistance was detected. CONCLUSION: Macrolide cross-resistance prevents the use of this entire class of antimicrobials when clarithromycin resistance is present. Tetracyclines and cefixime are possible alternative agents for the treatment of H. pylori infection in these patients.     

药品非临床研究管理规范

本文系统、全面地介绍了药品非临床研究管理规范（GLP）的概念、历史和发展沿革、主要内容及其在发展中国家和发达国家的实施情况。     

Novel investigational drugs active as single agents in multiple myeloma

Introduction: Multiple myeloma (MM) is a hematologic malignancy characterized by proliferation of malignant plasma cells. patient outcome has improved markedly over the last decades due to the introduction of novel therapeutic agents such as bortezomib, thalidomide and lenalidomide. However, MM still remains largely incurable and patients eventually become refractory to available treatments. To address this unmet medical need, a variety of new molecules are currently being developed in preclinical models and/or are being investigated in clinical studies.

Areas covered: We summarized available data on new investigational drugs showing anti-myeloma single-agent activity and that might have a role in the future therapeutic armamentarium against MM. Besides their single-agent activity, the synergic potential of these new agents with the currently approved drugs will be pivotal in their integration into consolidated MM backbone therapies. The drugs discussed include alkylators, new proteasome inhibitors, novel anti-CD38 monoclonal antibodies, Bcl-2 inhibitors, Cyclin-Dependent-Kinase inhibitor, Kinesin-spindle protein inhibitors, MEK1/2 inhibitors, AKT inhibitors and PIM-Kinase inhibitors.

Expert opinion: Isatuximab, oprozomib, melflufen, venetoclax and filanesib seem to be the most promising agents with single agent activity. Nevertheless, lack of clinical activity as single agent does not imply clinical inefficacy in combination treatments.     

Good Manufacturing Practice (GMP) voor de synthese van het actieve bestanddeel van geneesmiddelen

Naar een voordracht, gehouden doorE. M. Fry op 9 September 1980, ter gelegenheid van de Workshop of the Bulk Chemical Committee of the Pharmaceutical Manufacturers Association, Production and Engineering Section te Newark, USA. [De Pharmaceutical Manufacturers Association (PMA) is het Amerikaanse equivalent van de Nefarma. De heerFry is hoofd van de afdeling geneesmiddelenbereiding van het Bureau of Drugs binnen de Food and Drug Administration (FDA)].