《疫苗管理法》施行后疫苗生产环节法律问题探索

疫苗生产安全事故给疫苗接种带来了严重的信任危机,为此,《疫苗管理法》对疫苗生产安全作出新的规定.从疫苗生产环节入手,将《疫苗管理法》中有关生产环节的规定与《药品管理法》《药品管理法实施条例》《药品生产质量管理规范》《药品生产监督管理办法》中关于生产环节的规定予以比较,并分析新法的进步性,提出完善《疫苗管理法》关于生产环...     

《中华人民共和国疫苗管理法》的实施对预防接种工作的促进作用

作为我国第一部关于疫苗管理工作集大成的法律,《中华人民共和国疫苗管理法》具有里程碑式意义.从该法出台的背景与意义,对基层预防接种单位工作的要求等方面进行解读,分析比较该法的条款与既往法律法规的承袭与创新,强调日常接种行为需时刻遵法守法.通过关键内容解读,便于基层预防接种工作人员对该法有个初步认识.在开展免疫规划工作中尽...     

疫苗管理法中卫生相关配套规定的思考

接种疫苗是预防、控制以及消灭针对传染病的最有效手段[1]。中华人民共和国成立70年来,通过预防接种,尤其是免疫规划的实施,主要严重危害健康的疫苗针对传染病控制取得了巨大的进展,包括1994年后没有本土野病毒引起脊髓灰质炎,2016年后无白喉病例,麻疹等主要疾病与建国初期相比发病减少了98%以上[2]。     

中国首部疫苗管理法:用最严制度维护人民身体健康

作为我国第一部关于疫苗管理工作集大成的法律,《中华人民共和国疫苗管理法》具有里程碑式意义。从该法出台的背景与意义,对基层预防接种单位工作的要求等方面进行解读,分析比较该法的条款与既往法律法规的承袭与创新,强调日常接种行为需时刻遵法守法。通过关键内容解读,便于基层预防接种工作人员对该法有个初步认识。在开展免疫规划工作中尽量避免违法行为的发生,最终确保预防接种服务的安全、规范、科学,从而保障和促进公众健康。     

新修订《药品管理法》的六个特点

对新修订的《药品管理法》与原法进行了对比，分析了新法的6个显著特点。     

卫生部门在疫苗流通和预防接种中的职责与法律责任

2005年6月1日起施行的《疫苗流通和预防接种管理条例》（以下简称《条例》），是国务院依据《中华人民共和国药品管理法》和《中华人民共和国传染病防治法》授权制定的一一部行政法规，标志着我国疫苗流通和预防接种工作从过去的行政管理进入到法制管理的轨道，为预防、控制传染病的发生、流行，     

新的《中华人民共和国药品管理法》即将实施

一部全新的《中华人民共和国药品管理法》将在今年12月1日全部替代已经实施15年之久的现行药品管理法。国家药品监督管理局局长郑筱萸说,制定新法的出发点是适应我国市场经济发展的需要、解决当前药品生产经营领域出现的新问题和新情况。新法比现行法增加了46条条款,在严格药品质量管理、加大执法力度和药品价格、药品广告等群众关心的热点     

Monitoring the safety of quadrivalent human papillomavirus vaccine: findings from the Vaccine Safety Datalink

Background

In 7 large managed care organizations (MCOs), we performed a post-licensure safety assessment of quadrivalent human papillomavirus vaccine (HPV4) among 9-26 year-old female vaccine recipients between August 2006 and October 2009.

Methods

Sequential analyses were conducted weekly to detect associations between HPV4 exposure and pre-specified outcomes. The pre-specified outcomes identified by ICD-9 codes using computerized data at the participating MCOs included: Guillan-Barré Syndrome (GBS), stroke, venous thromboembolism (VTE), appendicitis, seizures, syncope, allergic reactions, and anaphylaxis. For rare outcomes, historical background rates were used as the comparison group. For more common outcomes, a concurrent unexposed comparison group was utilized. A standardized review of medical records was conducted for all cases of GBS, VTE, and anaphylaxis.

Results

A total of 600,558 HPV4 doses were administered during the study period. We found no statistically significant increased risk for the outcomes studied. However, a non-statistically significant relative risk (RR) for VTE ICD-9 codes following HPV4 vaccination of 1.98 was detected among females age 9-17 years. Medical record review of all 8 vaccinated potential VTE cases in this age group revealed that 5 met the standard case definition for VTE. All 5 confirmed cases had known risk factors for VTE (oral contraceptive use, coagulation disorders, smoking, obesity or prolonged hospitalization).

Conclusions

In a study of over 600,000 HPV4 vaccine doses administered, no statistically significant increased risk for any of the pre-specified adverse events after vaccination was detected. Further study of a possible association with VTE following HPV4 vaccination is warranted.     

Risk of medically attended local reactions following diphtheria toxoid containing vaccines in adolescents and young adults: A Vaccine Safety Datalink study

Three vaccines currently recommended for adolescents (Tdap, Td, and MCV4 meningococcal conjugate vaccine) contain diphtheria toxoid. While the safety of individual diphtheria toxoid containing vaccines has been evaluated, less is known regarding the safety of administration of two or more of these vaccines, either concomitantly or sequentially. This study evaluated the risk of medically attended local reactions in adolescents and young adults with varying patterns of receipt of diphtheria toxoid containing vaccines. In general the risk of medically attended local reactions was low and did not differ with concomitant or sequential administration of diphtheria toxoid containing vaccines.     

Uptake and safety of Hepatitis B vaccination during pregnancy: A Vaccine Safety Datalink study

IntroductionHepatitis B virus (HBV) infection acquired during pregnancy can pose a risk to the infant at birth that can lead to significant and lifelong morbidity. Hepatitis B vaccine (HepB) is recommended for anyone at increased risk for contracting HBV infection, including pregnant women. Limited data are available on the safety of HepB administration during pregnancy.ObjectivesTo assess the frequency of maternal HepB receipt among pregnant women and evaluate the potential association between maternal vaccination and pre-specified maternal and infant safety outcomes.MethodsWe examined a retrospective cohort of pregnancies in the Vaccine Safety Datalink (VSD) resulting in live birth outcomes from 2004 through 2015. Eligible pregnancies in women aged 12–55 years who were continuously enrolled from 6 months pre-pregnancy to 6 weeks postpartum in VSD integrated health systems were included. We compared pregnancies with HepB exposure to those with other vaccine exposures, and to those with no vaccine exposures. High-risk conditions for contracting HBV infection were identified up to one-year prior to or during the pregnancy using ICD-9 codes. Maternal and fetal adverse events were also evaluated according to maternal HepB exposure status.ResultsAmong over 650,000 pregnancies in the study period, HepB was administered at a rate of 2.1 per 1000 pregnancies (n = 1399), commonly within the first 5 weeks of pregnancy. Less than 3% of the HepB-exposed group had a high-risk ICD-9 code indicating need for HepB; this was similar to the rate among HepB unvaccinated groups. There were no significant associations between HepB exposure during pregnancy and gestational hypertension, gestational diabetes, pre-eclampsia/eclampsia, cesarean delivery, pre-term delivery, low birthweight or small for gestational age infants.ConclusionsMost women who received maternal HepB did not have high-risk indications for vaccination. No increased risk for the adverse events that were examined were observed among women who received maternal HepB or their offspring.     

Travelers and travel vaccines at six health care systems in the Vaccine Safety Datalink

BackgroundStudying the safety of travel vaccines poses challenges since recipients may be traveling during the risk window for adverse events and the identification of a suitable comparison group can also be difficult. The examination of traveler characteristics, travel vaccination patterns, and health care utilization using electronic health record (EHR) data can inform the feasibility of future travel vaccine safety studies.MethodsA retrospective cohort study of health plan members in the Vaccine Safety Datalink Project aged 9 months and older who had a travel-related encounter or received a travel vaccine from 2009 to 2018 was performed. Travel regions visited, travel duration, type of travel vaccine received (typhoid, yellow fever, Japanese encephalitis, rabies, and cholera), and timing of vaccination date before departure date were described. Sociodemographic information, clinical characteristics, and health care utilization were compared between travelers who received travel vaccines and travelers who did not.ResultsA total of 1,026,822 unique travelers departing from the United States were identified; 612,795 travelers received 898,196 doses of travel vaccines. The most commonly administered travel vaccine was typhoid vaccine and 77% of all travel vaccines were given more than one week prior to departure. Compared with travelers without travel vaccines, travelers with travel vaccines were overall similar but as a group were slightly younger, healthier, and had lower Hispanic representation. Health care utilization dramatically decreased during travel. Outpatient visits decreased from 294.8 visits per 10,000 person-days before travel to 24.2 visits per 10,000 person-days during reported travel dates.ConclusionsThrough the EHR information from almost a million travelers, a departure date and duration of travel were successfully captured for the majority of travelers with corresponding health care utilization data. Time after vaccination and prior to departure can potentially be used in the future to compare travelers who receive travel vaccines with travelers who do not receive travel vaccines when looking at adverse events of interest after vaccination.     

论我国新《药品管理法》中“假(劣)药”的认定与法律适用

通过比较分析2019年新修订的《药品管理法》中假药和劣药相关条款的主要变化,探讨新法中假(劣)药的内涵与界定,结合《疫苗管理法》《刑法修正案(十一)》和《民法典》中侵权责任等相关法律条款,研究生产、销售假(劣)药行为的法律适用。经比较发现,新修订的《药品管理法》重新定义了假(劣)药,取消按假(劣)药论处的概念,新增了两条禁止性规定,并调整了罚则。关于生产、销售假(劣)药行为的法律适用,首先,针对生产、销售假劣疫苗的违法行为,适用《疫苗管理法》,其设置了比生产、销售假(劣)药更严厉的处罚;其次,《刑法》中明确规定了生产、销售假药和劣药罪,最新修正案与《药品管理法》顺应衔接,新增了对违反药品管理秩序和药品使用单位工作人员提供行为的规制;再次,药物侵权是指缺陷药物造成生命健康损害而引发的侵权责任,在《民法典》中体现在产品责任和医疗损害责任。     

Severe combined immunodeficiency (SCID) and rotavirus vaccination: Reports to the Vaccine Adverse Events Reporting System (VAERS)

Background

Rotavirus vaccines are the only live vaccines recommended for infants in the US. Postmarketing reports have described severe gastroenteritis with vaccine viral shedding in infants who received rotavirus vaccine and were later diagnosed with SCID. The US Food and Drug Administration recently approved labeling changes for RotaTeq and Rotarix contraindicating administration to individuals with a history of SCID. We queried VAERS to characterize reports of SCID after rotavirus vaccination.

Methods

VAERS inclusion criteria included current US-licensed rotavirus vaccines, report dates from February 3, 2006 to January 15, 2010, and queries for the MedDRA preferred term “combined immunodeficiency” as well as any text containing the terms, “SCID” or “combined immunodeficiency.”

Results

We identified nine reports of SCID and rotavirus vaccination in infants between 3 and 9 months of age. All but one case presented with diarrhea among other symptoms. All infants were hospitalized and had workups leading to the SCID diagnosis. Stool rotavirus testing was positive in all cases and the virus was identified as the vaccine strain in six cases. Prolonged viral shedding was documented in five cases. No deaths were reported.

Conclusion

The aforementioned labeling changes were warranted given the risk posed by live rotavirus vaccine to individuals with SCID, as illustrated by these VAERS cases. Although congenital, SCID was not diagnosed in these infants until after rotavirus vaccination. Earlier identification of SCID (e.g., from expanded newborn screening or heightened clinical vigilance) could prevent inadvertent live rotavirus vaccine administration and also potentially result in earlier life-saving stem cell transplants.     

Value of an in-depth analysis of unpublished data on the safety of influenza vaccines in pregnant women

BackgroundUnpublished data can sometimes provide valuable information on the safety of biologic products.MethodsWe assessed information potentially available from regulatory authorities, manufacturers, and public health agencies. We explored 4 recently established vaccine registries, reviewed package inserts from 99 influenza vaccines, and contacted vaccine manufacturers and regulatory agencies for data on influenza vaccine safety in pregnant women.ResultsThe vaccine registries did not have sufficient data to analyze and there are problems with the quality of the information. The majority of package inserts provided no product-specific safety information for pregnant women, especially in less developed countries. The majority of available data come from reports gathered from passive adverse event reporting systems in the general population and reports of women enrolled in clinical trials of influenza vaccines who became pregnant at various times before or after receiving influenza vaccine. The information was not collected in a systematic manner, there are inconsistencies in the follow up of pregnant women and the available information about pregnancy outcomes. Considerable resources would be needed to systematically identify all of the information, try to obtain missing follow up information, and conduct analyses. There would be substantial limitations to any attempt to conduct a systematic analysis.ConclusionsThe value of trying to analyze unpublished data on the safety of influenza vaccine in pregnancy is limited and would require considerable resources to thoroughly investigate. Expanding efforts to identify and review unpublished data regarding the safety of influenza vaccines in pregnancy is not likely to produce information of high scientific value or information that could not be identified from publications and other publically available data.     

流行性感冒疫苗的免疫效果观察

目的 为了解流行性感冒(流感)疫苗免疫效果及安全性.方法 1999年1～2月在杭州市192名7～9岁儿童进行了疫苗接种前后免疫水平观察.结果 甲1型(H₂N₂)、甲3型(H₃N₂)和乙型流感HI抗体阳性保护率分别由1.56%、53.13%、52.60%上升到82.81%,87.50%和97.92%;平均抗体增长幅度分别是免疫前的18.9,2.9和5.69倍.副反应发生率为1.6%.结论 证实流感疫苗具有良好的免疫效果和安全性,值得进一步推广应用.     

重组(CHO细胞)乙型肝炎疫苗稳定性的研究

为了观察 10 μg/ml、2 0 μg/ml的重组中国仓鼠卵巢细胞 (CHO细胞 )乙型肝炎 (乙肝 )疫苗的稳定性 ,将 10 μg/ml、2 0 μg/ml疫苗放置 4℃ 2、3、4年后 ,分别接种NIH(美国国立卫生研究院 )小鼠 ,采用放射免疫试验 (RIA)检测血清中乙肝病毒表面抗体 (抗 HBs)。根据疫苗的ED50 算出相对效力。 10 μg/ml剂量疫苗相对效力平均值分别为 2年 1 83,3年 1 36 ,4年 0 83;2 0 μg/ml剂量疫苗相对效力平均值分别为 2年 1 91,3年 1 75 ,4年 1 75。结果表明 ,2 0 μg/ml疫苗的稳定性相对优于 10 μg/ml疫苗。