The year's new drugs & biologics, 2011

2011 was a good year in many respects for the pharmaceutical industry, especially regarding the approval and launch of several important new products. The FDA reported a record high rate of approvals during FY2011 (October 1, 2010-September 30, 2011), reflecting the agency's commitment to maintaining "a state-of-the-art drug approval process that brings important drugs to market quickly and efficiently" (1). While not all of the new drugs and biologics listed in FDA's fiscal year summary meet the criteria for inclusion in this article, most of them do, and hence are reviewed in the following pages. Also covered in this year's expanded article are new approvals and new launches in other global markets, line extensions and other developments of interest to the industry: generic drug approvals, product withdrawals and discontinuations, new developments in the area of orphan drugs and diseases, and more.     

香港澳门药品注册管理的比较研究

目的：将香港澳门的药品注册管理进行系统的比较研究,为内地药品到港澳上市提供参考。方法：运用文献研究和政策分析法,对港澳地区的药品注册管理体系、药品注册要求以及注册申报程序进行对比分析。结果：港澳的药品注册管理机制不同,香港的药品管理法律体系呈平行管理的特点,对中西药独立监管注册,中药实行中成药注册分类制度,并根据注册组别不同提交不同资料;而澳门的药品法律体系尚未统一,对药品集中注册管理,实行预先登记机制,中药实行中药预先许可制度。结论：内地药品在港澳注册上市,有利于提高内地企业的国际化和药物研发水平;内地企业在港澳申请注册时,应熟悉港澳药品注册管理政策,并与当地经销商合作,积极开展国际多中心临床试验;而提高内地企业药品研发质量,促进三地临床数据互认,有利于实现三地互利共赢的目标。     

Strategic balance of drug lifecycle management options differs between domestic and foreign companies in Japan

Introduction: Drug approvals and patent protections are critical in drug lifecycle management (LCM) in order to maximize drug discovery investment returns.

Area covered: We analyzed drug LCM activities implemented by 10 top companies in Japan, focusing on drug approvals and patent term extensions.

Expert opinion: Foreign companies acquired numerous drug approvals primarily for new molecular entities (NMEs), while Japanese companies mainly obtained approvals for improved drugs including new indications, and intensively extended patent terms. Furthermore, we discovered three factors likely responsible for differences in drug LCM strategies of Japanese and foreign companies: research and development capacities for drugs, drug lags of foreign-origin NMEs, and cooperation between Research and Development Departments and Intellectual Property Departments.     

香港特区药物采购策略与内地基本药物采购机制比较

目的:借鉴香港特区成功经验,为完善内地基本药物集中采购工作提供参考。方法:通过对香港特区医院管理局药物采购政策和策略与内地基本药物采购机制的分析比较,发掘可借鉴的经验,并提出内地需改进的建议。结果与结论:信息化建设是实现基本药物招采结合、量价挂钩采购模式的基础。建议建立全国范围的规范、统一、科学的药品分类方法和系统药物采购政策,采取多种采购方式和途径,保证基本药物供应,实现基本药物可及性要求。     

Herbal Medicines Induced Anticholinergic Poisoning in Hong Kong

In the present review, the main objective was to report the incidence and causes of herbal medicines induced anticholinergic poisoning in Hong Kong during 1989–2012 and to emphasize the importance of pharmacovigilance, investigations and preventive measures. Relevant papers, official figures and unpublished data were obtained from Medline search, the Department of Health and the Drug and Poisons Information Bureau. In the New Territories East (where ~20% of the Hong Kong population lived), the incidence of herbal medicines induced anticholinergic poisoning during 1989–1993 was 0.09 per 100,000 population. There were no confirmed cases during 1994–1996. In the whole of Hong Kong, the incidence during 2000–June 2005 was 0.03 per 100,000 population. Contamination of Rhizoma Atractylodis (50%) and erroneous substitution (42%) were the main causes. The incidence during 2008–2012 was 0.06 per 100,000 population. Contamination of non-toxic herbs (50%) and erroneous substitution (41%) were the main causes. In Hong Kong, contamination of non-toxic herbs by tropane alkaloids and substitution of Flos Campsis by toxic Flos Daturae Metelis were the predominant causes of herbal medicines induced anticholinergic poisoning. Systematic studies along the supply chain are necessary to identify the likely sources of contamination. If erroneous substitution of Flos Campsis by Flos Daturae Metelis could be prevented, 40% of herbal medicines induced anticholinergic poisoning would not have occurred. Regular inspection of the retailer, continuing education for the staff in the herbal trade and repeated publicity measures will also be required. Pharmacovigilance of herbal medicines should help determine the incidence and causes of adverse reactions and monitor the effectiveness of preventive measures.     

Erratum: Exploring the clinical and social determinants of prescribing anticholinergic medication for Chinese patients with schizophrenia

Human Psychopharmacology 2007; 22 : 173–180 DOI: 10.1002/hup.830 It has come to our attention that there was an error to one of the author names within this published article. The correct author listing and author affiliation is now published below. We apologise for this anomaly. Xiang Yu‐Tao^1,2, Weng Yong‐Zhen², Leung Chi‐Ming¹, Tang Wai‐Kwong¹, Ungvari Gabor Sandor^{1 1}Department of Psychiatry, Chinese University of Hong Kong, Hong Kong SAR, China ²Beijing Anding Hospital, Capital Medical University, Beijing, China     

Statistics on BCS Classification of Generic Drug Products Approved Between 2000 and 2011 in the USA

The Biopharmaceutics Classification system (BCS) classifies drug substances based on aqueous solubility and intestinal permeability. The objective of this study was to use the World Health Organization Model List of Essential Medicines to determine the distribution of BCS Class 1, 2, 3, and 4 drugs in Abbreviated New drug Applications (ANDA) submissions. To categorize solubility and intestinal permeability properties of generic drugs under development, we used a list of 61 drugs which were classified as BCS 1, 2, 3, and 4 drugs with certainty in the World Health Organization Model List of Essential Medicines. Applying this list to evaluation of 263 ANDA approvals of BCS drugs during the period of 2000 to 2011 indicated 110 approvals (41.8%) for Class 1 drugs (based on both biowaiver and in vivo bioequivalence studies), 55 (20.9%) approvals for Class 2 drugs, 98 (37.3%) approvals for Class 3 drugs, and no (0%) approvals for Class 4 drugs. The present data indicated a trend of more ANDA approvals of BCS Class 1 drugs than Class 3 or Class 2 drugs. Antiallergic drugs in Class 1, drugs for pain relief in Class 2 and antidiabetic drugs in Class 3 have received the largest number of approvals during this period.     

Electronic cigarette awareness and use among adults in Hong Kong

IntroductionElectronic cigarettes (e-cigarettes) have gained popularity rapidly in the Western world but data in the East are scarce. We examined the awareness and ever use of e-cigarettes, and reasons for e-cigarette use in a probability sample of adults in Hong Kong.MethodsCross-sectional data were collected in 2014 from Chinese adults aged 15–65 in Hong Kong (819 never smokers, 800 former smokers, 800 current smokers) via computer-assisted telephone interviews (response rate: 73.8%). Analysis was limited to a subset of 809 respondents (i.e., 357 never smokers, 269 former smokers, 183 current smokers) who were randomly selected to answer questions on e-cigarettes. Chi-square analyses compared e-cigarette awareness and ever use by gender, age, education, and cigarette smoking status. Multivariable logistic regression examined if e-cigarette awareness was associated with demographic variables and cigarette smoking status.Results75.4% of adults had heard of e-cigarettes, and 2.3% reported having used e-cigarettes. Greater awareness was associated with male gender and higher education. Ever use of e-cigarettes was higher among males (3.6%, p = .03), younger adults (aged 15–29, 5.2%, p = .002), and current cigarette smokers (11.8%, p < .001). Common reasons for using e-cigarettes were curiosity (47.4%), the stylish product design (25.8%), and quitting smoking (13.6%).ConclusionsAwareness of e-cigarettes was widespread in Hong Kong. Although the use of e-cigarettes was low, its relation with younger age and current smoking is of concern. Health surveillance of e-cigarette use is needed. Interventions should target young adults and cigarette smokers, and address the marketing messages, especially the effect of e-cigarettes on smoking cessation.     

Drug-related problems as a cause of hospital admissions in Hong Kong

The importance of drug-related problems as a cause of hospital admissions in Hong Kong was studied in 925 patients admitted to two general medical wards at the Prince of Wales Hospital between November 1992 and February 1993. Drug-related problems were judged to be the main reason for hospital admissions in 88 patients (9.5 per cent). These were adverse drug reactions (n = 57), drug poisoning (n = 22) and treatment failure consequent to noncompliance or inappropriate reduction in dosage (n = 9). The most important adverse drug reactions were gastrointestinal hemorrhage (36.8 per cent) and hypoglycemia (24.6 per cent), and the three drug classes that were most commonly involved were non-steroidal anti-inflammatory drugs (NSAIDs) (aspirin 12.3 per cent, non-aspirin 28.1 per cent), sulphonylureas (19.3 per cent) and diuretics (12.3 per cent). Drug-related problems are an important cause of hospital admissions, and much of the drug-induced illnesses in Hong Kong could be preventable if particular attention was given to NSAID and sulphonylurea therapy. Patients should also be educated about the importance of good drug compliance.     

我国大陆及港澳台地区医院开展用药教育现状比较

目的介绍我国澳门、台湾及香港地区医院实施用药教育的相关举措,以及大陆实施用药教育的状况。方法通过文献检索及查阅相关资料。结果与澳门、台湾及香港地区相比,我国大陆地区公众在医院领取药物时接受的指导和咨询相对欠缺,社会药房也几乎不为公众提供用药教育和咨询。结论总结澳门、香港及台湾地区医院推行用药教育模式,借以探索出一条适合大陆地区的用药教育发展模式。     

我国香港、澳门、台湾地区与大陆药学执业人员的比较

目的:供我国大陆药学执业人员的管理者及其他相关人员参考。方法:对我国香港、澳门、台湾地区与大陆药学执业人员的有关情况进行比较和分析。结果与结论:我国香港、澳门、台湾地区与大陆在药学执业人员的管理法律依据、管理机构、分类及数量、分布、准入资格、教育和继续教育等方面均存在差异,大陆可以借鉴香港、澳门、台湾地区的可取之处,进一步完善对药学执业人员的管理。     

Specialty pharmacy cost management strategies of private health care payers

BACKGROUND: The rate of increase in spending on specialty pharmaceuticals is outpacing by far the rate of increase in spending for other drugs. OBJECTIVE: To explore the strategies payers are using in response to challenges related to coverage, cost, clinical management, and access of specialty pharmaceuticals and to describe the potential implications for key stakeholders, including patients, physicians, and health care purchasers. METHODS: Sources of information were identified in the course of providing consulting services in the subject area of specialty pharmaceuticals to health plans, pharmacy benefit managers, employers, and pharmaceutical manufacturers. RESULTS: Specialty pharmaceuticals represent the fastest growing segment of drug spending due to new product approvals, high unit costs, and increasing use. Health care payers are faced with significant challenges related to coverage, cost, clinical management, and access. A variety of short- and long-term strategies have been employed to address these challenges. CONCLUSIONS: Current management techniques for specialty pharmaceuticals often represent a stop-gap approach for controlling rising drug costs. Optimum cost and care management methods will evolve as further research identifies the true clinical and economic value of various specialty pharmaceuticals.     

建立香港中药不良反应监测系统,发挥中医药在药物滥用防治中的作用

药物滥用是造成药物不良反应的重要原因之一,我国将滥用麻醉药品等称为"吸毒",是形成药物依赖性的主要原因。药物依赖性包括生理依赖和     

Book Reviews

Sucht Und Missbrauch—Edited by F. Laubenthal—Georg Thieme Verlag. Stuttgart, 1964

Utopiates—Richard Blum & Associates— Atherton Press, New York, 1965.

Under The Rug: THE DRUG PROBLEM IN HONG KONG—Michael G. Whisson—Hong Kong. The South China Morning Post. Ltd., by the Hong Kong Council of Social Service. 1965, 249 pp.

The Psychotherapy Of Alcoholism—G. V. Zenevich and S. S. Libikh—The Library of the General Physician. Publishing Institute “Medicine.” Leningrad, 1965, 146 pages (Russian).     

Epidemiology and potential risk factors of drug-related problems in Hong Kong paediatric wards

Aims

A drug-related problem (DRP) is ‘an event or circumstance involving drug therapy that actually or potentially interferes with the desired health outcome’. The extent and characteristics of DRPs in children in Hong Kong are unknown. The aim of this study was to determine the epidemiology of and identify risk factors for DRPs in hospitalized children in Hong Kong.

Methods

This was a prospective cohort study in children aged 0–18 years who were admitted to a medical ward, paediatric intensive care unit or neonatal intensive care unit of seven Hong Kong hospitals, during a 3 month period. Patients'' charts, medical records and laboratory data were reviewed daily to identify DRPs; their preventability and severity were assessed. Logistic regression was used to analyse potential risk factors associated with the incidence of DRPs.

Results

Three hundred and twenty-nine children (median age, 2 years; interquartile range, 0 months to 9 years) were included. In total, 82 DRPs were experienced by 69 patients. The overall incidence of DRPs was 21.0% (95% confidence interval, 16.7–25.8%). The incidence was higher in neonatal and paediatric intensive care units than medical wards. Dosing problems were the most frequently reported DRPs (n = 35; 42.7%), followed by drug choice problems (n = 19; 23.2%) and adverse drug reactions (n = 11; 13.4%). Sixty-seven (81.7%) DRP cases were assessed as preventable, 42 (51.2%) as minor and 40 (48.8%) as moderate. The number of prescribed drugs and ‘certain infectious and parasitic diseases’ were potential risk factors for occurrence of DRPs.

Conclusions

Drug-related problems were common in hospitalized children in this study in Hong Kong; the most frequent were dosing and drug choice problems, and the majority of them were preventable. Polypharmacy and ‘certain infectious and parasitic diseases’ were potential risk factors.     

药品连续制造全球监管发展现状与思考

目的：在连续制造技术越来越多地应用在药品领域这一背景下,综述相关法规指南从概念探索、 正式发起至发布的发展历程,介绍全球多个采用连续制造技术生产药品获批上市的概况,探讨促进我国业界和监管机构借鉴全球药品连续制造发展经验。方法：通过对比传统的批量制造技术以分析连续制造具有的优势和面临的挑战,结合对全球监管指南制定过程中各监管机构对策的梳理,研究相关共识的发展考量和意义。结果：药品连续制造监管发展已经进入了新的时代,我国相关法规指南的制定和产业技术水平提升需要借鉴全球发展的经验,特别是国际人用药品注册技术协调会及美、欧、日等国家药品监督管理机构或国际组织的现有指南在批定义、工艺验证、稳定性等方面的监管对策,为该新兴技术的监管科学研究提供理论基础。结论：通过对药品连续制造全球监管发展现状的综述和思考,为我国相关法规、技术指南和标准的制定提供参考,并希望为产业发展发挥促进作用。     

A Multidisciplinary Evaluation of Barriers to Enrolling Cancer Patients into Early Phase Clinical Trials: Challenges and Patient-centric Recommendations

Introduction: Early phase clinical trials are the first clinical research step to bringing new cancer therapeutics to patients. At this stage, a new drug’s safety, dosing, and scheduling profiles are established as the main endpoints. However, excellent responses due to biomarker-guided and immune checkpoint trials in early phase have resulted in direct approvals of new anti-cancer drugs. Despite doubling of the success rate of new drug approvals, many barriers exist to expeditiously bring active new drugs to the clinic.

Areas covered: This review covers roles of members of the early phase program and the challenges they face in enrolling advanced cancer patients to trials. Practical solutions are provided from the perspective of the investigators, regulatory, investigational pharmacy, research nurses, clinical research coordinators, budgets, contracts, and data management.

Expert opinion: We are witnessing a burgeoning era in drug development with rapid approval of efficacious drugs. This is achieved by a strong collaboration between investigators, academic institutions, pharmaceutical sponsors, scientists, Food and Drug Administration (FDA), and community practices. Herein, we discuss some of the challenges faced by early phase clinical trials programs and discuss methods of improvement.     

Is Hong Kong experiencing normalization of adolescent drug use? Some reflections on the normalization thesis

The upsurge of consumption of party drugs among adolescents in recent years in Hong Kong has been part of the global trend of adolescent recreational use of drugs at rave parties, discos and similar party settings. Scholars in Western societies have recently proposed the thesis of "normalization of adolescent drug use" to describe such a trend. The normalization thesis points at three major aspects of the normalization phenomenon, namely, a rapid increase of the prevalence of drug use in young people, the widespread popularity of recreational drug use that is closely linked with the recent arrival of dance club culture, and a receptive attitude towards drug use as a normal part of leisure. This article aims to examine whether the normalization thesis can be applied to analyze the situation of adolescent drug use in Hong Kong. Data are drawn from official statistics and a recent survey conducted in 2002-2004 of drug use of Hong Kong marginal youths (N = 504). The case of Hong Kong only partially supports the thesis. Our findings show that the normalization of drug use among young people has occurred in Hong Kong, but the extent of normalization is smaller than those in Western societies like the United Kingdom. They also suggest that a recognition of possible cultural differences may be complementary to the normalization thesis. Limitations of the study are also noted.     

Is Hong Kong Experiencing Normalization of Adolescent Drug Use? Some Reflections on the Normalization Thesis

The upsurge of consumption of party drugs among adolescents in recent years in Hong Kong has been part of the global trend of adolescent recreational use of drugs at rave parties, discos and similar party settings. Scholars in Western societies have recently proposed the thesis of “normalization of adolescent drug use” to describe such a trend. The normalization thesis points at three major aspects of the normalization phenomenon, namely, a rapid increase of the prevalence of drug use in young people, the widespread popularity of recreational drug use that is closely linked with the recent arrival of dance club culture, and a receptive attitude towards drug use as a normal part of leisure. This article aims to examine whether the normalization thesis can be applied to analyze the situation of adolescent drug use in Hong Kong. Data are drawn from official statistics and a recent survey conducted in 2002–2004 of drug use of Hong Kong marginal youths (N = 504). The case of Hong Kong only partially supports the thesis. Our findings show that the normalization of drug use among young people has occurred in Hong Kong, but the extent of normalization is smaller than those in Western societies like the United Kingdom. They also suggest that a recognition of possible cultural differences may be complementary to the normalization thesis. Limitations of the study are also noted.     

An update on the current status and prospects of nitrosation pathways and possible root causes of nitrosamine formation in various pharmaceuticals

Over the last two years, global regulatory authorities have raised safety concerns on nitrosamine contamination in several drug classes, including angiotensin II receptor antagonists, histamine-2 receptor antagonists, antimicrobial agents, and antidiabetic drugs. To avoid carcinogenic and mutagenic effects in patients relying on these medications, authorities have established specific guidelines in risk assessment scenarios and proposed control limits for nitrosamine impurities in pharmaceuticals. In this review, nitrosation pathways and possible root causes of nitrosamine formation in pharmaceuticals are discussed. The control limits of nitrosamine impurities in pharmaceuticals proposed by national regulatory authorities are presented. Additionally, a practical and science-based strategy for implementing the well-established control limits is notably reviewed in terms of an alternative approach for drug product N-nitrosamines without published AI information from animal carcinogenicity testing. Finally, a novel risk evaluation strategy for predicting and investigating the possible nitrosation of amine precursors and amine pharmaceuticals as powerful prevention of nitrosamine contamination is addressed.