国外仿制药参比制剂选择简介及对我国的启示

目的：为完善我国仿制药一致性评价中参比制剂选择机制和程序提供参考,为仿制药企业在应用选择参比制剂时提供思路。方法：详细介绍了美国FDA有关参比制剂选择指南草案的最新描述,以及欧盟、日本和WHO对于参比制剂的相关要求。结合我国现阶段仿制药一致性评价工作实际,为完善参比制剂选择程序提出建议。结果与结论：美国详细规定了仿制药参比制剂的选择思路和实际操作程序,为我国仿制药参比制剂的选择提供了新的思路。我国正处于仿制药一致性评价参比制剂遴选的关键时期,制定全面、完善的参比制剂遴选体系和机制,有助于规范参比制剂的选择程序,加快一致性评价工作进程,提升我国仿制药一致性评价参比制剂选择的科学性和完整性。     

Information from US FDA

Vaccines have contributed to a significant reduction in many childhood infectious diseases, such as diphtheria, measles, andHaemophilus influenzaetype b (Hib). Some infectious diseases, such as polio and smallpox, have been eliminated in the United States due to effective vaccines. It is now rare for children in the United States to experience the devastating and often deadly effects of these diseases that were once common in the United States and other countries with high vaccination coverage.     

A comprehensive review on Brigatinib – A wonder drug for targeted cancer therapy in non-small cell lung cancer

The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90?mg of brigatinib for 7?days and then 180?mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.     

Expanded access to investigational drugs: balancing patient safety with potential therapeutic benefits

Introduction: Expanded access is the use of an investigational product by patients with serious medical conditions without participation in a clinical trial. It is a complicated process involving the collaboration of many parties and pharmaceutical companies. Ongoing efforts focus on accelerating expanded access procedures in the best interest of patients with cancer.

Areas covered: We review the regulatory and ethical challenges encountered in efforts to optimize expanded access.

Expert opinion: In the era of personalized medicine, patients may benefit from novel therapeutic agents that demonstrate encouraging results in early studies. However, drug approval is a lengthy and cumbersome procedure that might exceed the time frame of a life-threatening disease. Expanded access provides options to patients with unmet needs. It may provide informative safety and efficacy data to the manufacturers and the scientific and regulatory organizations.

Ongoing efforts are being made by global governmental and scientific committees, regulatory agencies, and patient organizations to address the ethical and regulatory issues and to optimize the expanded access process. Their goal is to expand access to promising novel drugs for individual patients and to accelerate the necessary procedures while preserving patient safety.     

Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination

New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5–9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2–27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7–157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4–90.3), and Enders’Edmonston (IRR: 8.5; 95% CI: 1.9–38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3–87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the rapid post-marketing evaluation of safety signals for serious and rare adverse events for new and existing vaccines in all settings, including LMICs.     

FDA对复方激素类避孕药说明书的要求

美国食品药品管理局（FDA）于2017年12月发布了"复方激素类避孕药说明书指导原则"。该指导原则对这类药物说明书各个项目提出了详细而具体的要求。介绍该指导原则的主要内容,期待对我国这类药物说明书充实内容、补充重要信息和准确反映目前的科学认识水平有所帮助。     

FDA对皮肤外用药活性成分人体最大用量试验的要求

美国食品药品管理局（FDA）于2018年5月发布了“考虑列入OTC专论的外用药活性成分的最大用量试验：研究要点和考虑的因素供企业用的指导原则”。最大用量试验（MUsT）是评估外用药体内生物利用度的标准方法,该指导原则对MUsT许多研究要点提出了具体的建议。详细介绍该指导原则的主要内容,期待对我国这方面的研究和监管有益。     

FDA对全身用抗菌药说明书敏感性试验解释标准管理的新举措——互联网+STIC

最近美国食品药品管理局（FDA）建立了抗菌药敏感性试验解释标准（STIC）网页,同时规定药品说明书不再列出STIC相关资料,而改为告知查询该网页,从而加速STIC信息传递,促进临床合理选用抗菌药。为此,FDA于2017年12月发布了《全身用抗菌和抗真菌药物：NDAs和ANDAs说明书敏感性试验解释标准指导原则》,详细介绍该指导原则的主要内容,以期我国早日实施这种高效的互联网+STIC管理模式。     

Metabolic syndrome: pathogenesis, medical care and dental implications

BACKGROUND: The dental literature contains little information about metabolic syndrome (MetS) and its dental implications. TYPES OF STUDIES REVIEWED: The authors conducted a MEDLINE search for the period 2000 through 2005, using the term "metabolic syndrome" to define its pathophysiology, medical treatment and dental implications. RESULTS: MetS is the co-occurrence of abdominal obesity, hyper-triglyceridemia, reduced high-density lipoprotein cholesterol levels, hypertension and impaired fasting glucose, which results from consumption of a high-calorie diet and decreased levels of physical activity superimposed on the appropriate genetic setting. Components of MetS synergistically promote the development of atherosclerosis, resulting in myocardial infarction and stroke. CLINICAL IMPLICATIONS: Deteriorating oral health status is associated with worsening of the atherogenic profile. Tooth loss often results in chewing difficulties because of inadequate occlusive surfaces and may lead to alterations in food selection and dietary quality. This, in turn, adversely affects body composition and nutritional status, both of which are related to vascular health. Dentists should develop treatment plans that preserve and restore the dentition, thus ensuring maximum masticatory efficiency and affording patients the optimum opportunity to consume food that will not foster atherogenesis.     

FDA医疗器械设备问题术语集的应用研究

美国食品药品监督管理局（FDA）于2009年7月开始实施新的设备问题术语集。通过阐述FDA设备问题术语集的实施概况及其术语集结构,基于美国MAUDE数据库论证了该设备问题术语集对医疗器械风险评价的实际意义,分析了FDA设备问题术语集对于我国监测实情的应用难度,并结合监测现状提出了借鉴FDA设备问题术语集的实施建议,以期对我国设备故障术语集的建立提供有益思路。