细胞治疗产品GMP厂房、设施与设备工程设计要点

目的:细胞治疗主要的作用是用在肿瘤的治疗上,虽然作用非常大,但由于是新兴领域,在细胞治疗产品的制备上还处于商业化初期阶段,从CMC研究到产业化生产,每一步都容不得出错。方法:本文就细胞治疗产品生产的特殊性,结合其生产工艺流程和实际项目设计案例,重点分析了其GMP厂房、设施与设备工程设计要点,如GMP厂房平面布局设计、空调系统设计、公用设施系统设计、设备等。结果:搭建专属细胞治疗产品制备的GMP车间,从而提高其制备的效率和质量。结论:细胞治疗产品基于产品特性,决定了工艺流程设计的复杂性和辅助系统的特殊要求,其GMP生产车间的工艺布局和厂房设施应充分考虑场地选择、生产品种和批次、工艺、产品研发生产阶段等因素,合理合规的厂房设计才能确保产品的安全性、合法性。

“虚拟仿真-GMP实训-产教融合”三位一体协同创新育人模式探索与实践

在新工科和“双一流”建设的契机下,围绕“培养具有历史使命感和社会责任心,富有创新精神和实践能力的各类创新型、应用型、复合型优秀人才”的目标,根据工程教育认证要求,结合湘潭大学制药工程专业的实际情况,构建“虚拟仿真-GMP实训-产教融合”三位一体协同创新育人平台。以人才培养为核心,优化实践教学培养体系,建设高水平的教师队伍,加强虚实结合平台建设,注重产教融合,培养具有解决复杂工程问题的制药技术人才。

兽用中化药生产企业GMP监督检查情况分析与思考

对近年来中国兽医药品监察所组织实施的兽用中化药企业GMP监督检查发现的缺陷项目进行统计和分析,研究企业在生产质量管理中存在的主要问题并提出建议,以期帮助兽药生产企业提高自身GMP执行水平,确保产品质量,并为兽药监管部门提供参考。

安徽省实施新版兽药GMP的情况分析

阐述了安徽省实施新版兽药GMP具体情况,在三年多的实施过程中,共有45家兽药企业通过验收。整理汇总了验收前企业遇到的具体问题和主管部门采取的措施,验收过程中检查组提出的共性问题及验收后“回头看”发现的实际运行中的具体问题。安徽省实施新版兽药GMP情况只是全国新版兽药GMP实施情况的缩影,通过汇总问题,分析原因总结经验,以期为新版兽药GMP高质量运行提供参考。

高职《药品生产GMP实务》教学改革实践研究

GMP即为《药品生产质量管理规范》(Good Manufacturing Practice of Medical Products),是药品生产和质量管理的基本准则。传统《药品生产GMP实务》课程教学中存在教学内容与企业人才需求脱节、教学方法导致学生学习兴趣不高、单一评价模式无法体现学生岗位能力水平等问题。《药品生产GMP实务》课程以质控岗位职业能力培养为实施导向,以基于工作过程的项目化教学、药物制剂生产1+X证书培训和三大结构化项目互融合为实施载体,以线上教学和线下教学相互联动、思政教育与专业教学有机结合为实施手段,推行“三对接、十路径、三全赋能”模式,创设“探查引测编验评改结拓”十步路径教学法,着眼于学生的持续进步和终身成长,实施全员全程全方位精技赋能,实现“立德树人”目标。

基于质量风险管理的我国药品GMP检查研究

目的将质量风险管理的理念和方法运用到我国GMP管理非常必要,我国GMP检查将依风险发起,建立统一规范的质量风险管理模型将有助于我国GMP监管的发展和完善。方法首先,介绍了质量风险管理;然后,分析了几个典型国家和地区质量风险管理在GMP检查中的应用情况,同时分析了我国GMP的发展和现状,依据质量风险管理的原则提出了对策建议。结果与结论我国应该出台具有指南性的质量风险管理文件,从企业自身和监管部门对风险进行识别和评估,根据风险评估确定检查时间和频率。建立药品全生命周期风险管理模型,同时加强国际间的合作,签订国际GMP互认协议。

GMP在白酒自动化酿造工厂中的运用

随着我国科技发展和工业水平的不断提升,自动化设备和机械在白酒生产行业中的应用也越来越广泛,使用机器设备操作代替人工操作,对白酒生产企业来说既能够增加生产效率又能够降低生产成本,是白酒生产行业未来的必然发展趋势。白酒在中国有着悠久历史和重要地位,随着国人的生活水平不断提升,需求也不断加大,传统的白酒酿造产量低、人工生产成本高、招工难等问题出现,已经不能满足供应,白酒生产由传统手工酿造向自动化酿造转型迫在眉睫,随之而来的食品安全和质量问题是白酒生产企业亟待解决的问题。本文所列举的GMP内容是白酒酿造自动化生产企业达到安全、优质产品的基本条件,为白酒酿造自动化生产提供了借鉴和参考。

GMP课程“四位一体”教学模式新探究

“药品生产质量管理规范(GMP)”作为药学专业本科生的专业课,是一门在理论知识框架内具有高度实践性的重要课程。但由于该课程具有较大的内容量、繁杂的知识点、较高的实践性、较强的操作性要求等特点,使得其存在较多授课难题。为此,围绕这些问题,同时结合学校软硬件设施的具体情况,提出“四位一体”教学新模式。在该模式中,理论知识框架搭建、课程模拟实验、GMP仿真实习以及创新式课程考核将贯穿于整个教学过程中,从而在达到理论与实践相结合的前提下,最终实现高层次制药技术应用型人才培养的目的。

Association between Meeting 24-Hour Movement Guidelines and Psychological Features of Chinese Emerging Adults

Background:Emerging adulthood is a pivotal life stage,presenting significant psychological and social changes,such as decreased sociability,depression,and other mental health problems.Previous studies have associated these changes with an unhealthy lifestyle.The 24-h movement guidelines for healthy lifestyles have been developed to promote appropriate health behaviors and improve individual wellness.However,the relationship between adherence to the 24-h movement guidelines and different characteristics of Chinese emerging adults is yet to be explored.This cross-sectional study aimed to investigate the association between adherence to the 24-h movement guidelines and four characteristics(self-exploration,instability,possibilities,and responsibility)of Chinese emerging adults.Methods:Overall,1,510 Chinese emerging adults aged 18–29 years were included in this study.Each participant completed a self-administered questionnaire that included questions on adherence to the 24-h movement guidelines(physical activity,sedentary behavior,and sleep)and the inventory of dimensions of emerging adulthood.Multivariable logistic regression analysis was employed to investigate the associations between adherence to the 24-h movement guidelines and each of the four characteristics.Results:The proportion of participants who adhered to the 24-h movement guidelines was 31.72%.Multiple regression analysis revealed a significantly negative relationship between adhering to more guidelines and instability(β=−0.51,p<0.001).A statistically significant association was observed between instability and meeting only sedentary behavior(β=−1.27,95%confidence interval[CI]:[−2.32,−0.24],p=0.02),sedentary behavior+sleep(β=−1.30,95%CI:[−2.24,−0.35],p<0.01),and physical activity+sedentary behavior(β=−1.08,95%CI:[1.94,−0.21],p=0.02)guidelines.Further,positive and significant associations were observed between possibilities and meeting the guidelines for only physical activity(β=0.70,95%CI:[0.14,1.27),p=0.01),only sleep(β=0.61,95%CI:[0.01,1.21],p=0.04),physical activity+sedentary behavior(β=0.56,95%CI:[0.04,1.07),p=0.01),and physical activity+sleep(β=0.76,95%CI:[0.23,1.27],p=0.01).Conclusions:These findings suggest that adherence to the 24-h movement guidelines was associated with instability in Chinese emerging adults.Future studies are warranted to verify our findings to highlight the importance of maintaining a heath lifestyle to promote health in emerging adulthood.

我国中药成方制剂与加拿大天然健康产品GMP比较

目的探究我国与加拿大在生产质量管理规范体系中对中药质量的把控情况,并探索两国中药药品生产质量管理规范(GMP)的差异。方法对我国中药制剂GMP文件与加拿大天然健康产品GMP指导文件进行比较研究,主要从指导文件的框架、方向和文件细则等方面进行对比,分析我国中成药GMP质量管理体系与加拿大天然健康产品质量规范各自的特点。结果我国GMP文件和加拿大GMP文件在中药产品的管理结构、机构和人员的设置、中药原材料及产品等方面均存在区别。结论我国GMP文件与加拿大GMP文件存在差异,可为我国中药GMP管理体系的进一步合理应用提供参考。

安徽省高风险药品生产企业依职责GMP符合性检查风险分析与对策

为推动高风险药品生产企业持续符合药品生产质量管理规范(GMP),对近3年安徽省开展的高风险药品生产企业依职责GMP符合性检查的缺陷项目进行统计分析。共汇总缺陷项目1408项,包括严重缺陷7项、主要缺陷88项、一般缺陷1313项,主要分布于质量控制与质量保证、文件管理、无菌药品附录等方面。高风险药品生产企业应从落实主体责任、强化污染控制策略、建立长效培训机制、严格供应商管理、完善确认与验证、加强产品质量回顾分析等方面着手持续保障药品质量安全。

Assessment of International GNSS Service Global Ionosphere Map products over China region based on measurements from the Crustal Movement Observation Network of China

The global ionosphere maps(GIM)provided by the International GNSS Service(IGS)are extensively utilized for ionospheric morphology monitoring,scientific research,and practical application.Assessing the credibility of GIM products in data-sparse regions is of paramount importance.In this study,measurements from the Crustal Movement Observation Network of China(CMONOC)are leveraged to evaluate the suitability of IGS-GIM products over China region in 2013-2014.The indices of mean error(ME),root mean square error(RMSE),and normalized RMSE(NRMSE)are then utilized to quantify the accuracy of IGS-GIM products.Results revealed distinct local time and latitudinal dependencies in IGS-GIM errors,with substantially high errors at nighttime(NRMSE:39%)and above 40°latitude(NRMSE:49%).Seasonal differences also emerged,with larger equinoctial deviations(NRMSE:33.5%)compared with summer(20%).A preliminary analysis implied that the irregular assimilation of sparse IGS observations,compounded by China’s distinct geomagnetic topology,may manifest as error variations.These results suggest that modeling based solely on IGS-GIM observations engenders inadequate representations across China and that a thorough examination would proffer the necessary foundation for advancing regional total electron content(TEC)constructions.

Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1^(−/−)mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Olympic Games and 24-hour movement behaviors:A match worth making

1.Background The Olympic motto,"Faster,Higher,Stronger-Together",represents the pursuit of athletic excellence,united as a global community."Excellence,respect and friendship"are the Olympic values.Both the motto and values are multifaceted and holistic in nature,and all-encompassing in their reach while recognizing no single entity rises above the others.Collectively,these foundational statements anchor the Olympic movement in its quest to build a better world through sport.

The osteoclastic activity in apical distal region of molar mesial roots affects orthodontic tooth movement and root resorption in rats

The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment.However,the sensitivity of existing detection techniques is not sufficient,and the criteria for evaluating optimal force have not been yet established.Here,by employing 3D finite element analysis methodology,we found that the apical distal region(A-D region)of mesial roots is particularly sensitive to orthodontic force in rats.Tartrate-resistant acidic phosphatase(TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams(g),leading to alveolar bone resorption and tooth movement.When the force reached 80 g,TRAP-positive osteoclasts started appearing on the root surface in the A-D region.Additionally,micro-computed tomography revealed a significant root resorption at 80 g.Notably,the A-D region was identified as a major contributor to whole root resorption.It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement,inclination,and hyalinization.These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model.Collectively,our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients’orthodontic treatment.

Towards precision 24-hour movement behavior recommendations—The next new paradigm?

1.Background The importance of physical activity(PA)for health is unequivocal.^(1)Accordingly,population-based recommendations for exercise,and more recently public health guidelines for PA,have been developed and released by authoritative groups for many decades.^(2)Such guidelines emerged with leadership from the exercise physiology discipline and were rooted in,and loyal to,the importance of moderate-to-vigorous intensity PA(MVPA)or exercise.

Modifying the progression of Parkinson's disease through movement interventions:multimodal quantification of underlying mechanisms

Introduction:Parkinson’s disease(PD)is the most common neurodegenerative movement disorder.The pathological hallmark is the progressive loss of dopaminergic neurons of the substantia nigra pars compacta,which is accompanied by widespread alterations in the structu re and function of distributed brain networks.Togethe r,these processes cause a variety of motor symptoms such as bradykinesia,rigidity,tremor,gait disorders,or difficulties in fine motor control(Bange et al.,2022).

Dual roles of the amygdala-hippocampus circuit in the regulation of rapid eye movement sleep and depression symptoms by repetitive transcranial magnetic stimulation in patients with insomnia

To the editor:It is commonly reported that people with insomnia often experience comorbid emotional disorders,such as mood and anxiety disorders.12 A study found that fragmented rapid eye movement(REM)sleep in individuals with insomnia is associated with higher Beck Depression Inventory(BDI)scores.3 REM sleep architecture disruption is a typical symptom of insomnia.

关于药品GMP管理中洁净服存在主要风险点的探讨

对于药品生产来说,为了减少人员对洁净环境的污染,同时考虑到操作员工健康防护的需求,所有进入洁净区人员均需要穿戴洁净服,本文基于中国GMP、EUGMP、FDAcGMP等法规要求,同时结合多年在GMP检查过程中洁净服管理方面的经验,从洁净服全生命周期管理中的关键点和策略进行剖析,以评估洁净服使用过程中可能带来的潜在质量风险,为业界对洁净服规范化管理提供参考。

Engineering The Neck Hinge Reshapes The Processive Movement of Kinesin-3

Objective In kinesin-3,the neck coil correlates with the following segments to form an extended neck that contains a characteristic hinge diverse from a proline in KIF13B to a long flexible linker in KIF1A.The function of this neck hinge for controlling processive movement,however,remains unclear.Methods We made a series of modifications to the neck hinges of KIF13B and KIF1A and tested their movement using a single-molecule motility assay.Results In KIF13B,the insertion of flexible residues before or after the proline differentially impacts the processivity or velocity,while the removal of this proline increases the both.In KIF1A,the deletion of entire flexible neck hinge merely enhances the processivity.The engineering of these hinge-truncated necks of kinesin-3 into kinesin-1 similarly boosts the processive movement of kinesin-1.Conclusion The neck hinge in kinesin-3 controls its processive movement and proper modifications tune the motor motility,which provides a novel strategy to reshape the processive movement of kinesin motors.