Abstract:The authenticity and validity of clinical trial data are paramount in drug development.In the past years,the international acceptance of clinical trial date from China has been limited,making it a critical yet challenging endeavor to enhance their global recognition.This paper introduces the evolution of China's clinical trial system,summarizes and analyzes the current challenges and obstacles hindering the international acceptance of its clinical trial data,and offers suggestions for future development.

Abstract:Objective:To evaluate the cost-effectiveness of Jiuwei zhike oral liquid versus jizhi syrup in the treatment of acute bronchitis with cough due to windheat syndrome.Methods:The short-term cost-effectiveness analysis was conducted from the perspective of Chinese health system based on the phase Ⅲ clinical study of jiuwei xhike oral liquid.The health outcome was evaluated by cough disappearance time.The single factor and possibility sensitivity analysis were performed for key indicators.Furthermore,the disappearance rate of throat-drying symptom was used as the efficacy indicator in the scenario analysis to verify the robustness of the base case analysis.Results:The average cough disappearance time was shortened by 0.46 days while the cost was 26.41 Yuan higher.The incremental cost-effectiveness ratio value of jiuwei zhike oral liquid compared with jizhi syrup was 57.7 Yuan per day,which was less than China's daily per capita disposable income in 2023.Possibility sensitivity analysis showed that when the willingness to pay threshold was set up as 107.4 Yuan,jiuwei zhike oral liquid had a 93.8％chance of being more cost-effective compared to jizhi syrup.Results of scenario analysis was consistent with base case analysis results.Conclusion:jiuwei zhike oral liquid is cost-effective for acute bronchitis patients with cough due to windheat syndrome.

Abstract:The Chinese government prioritizes the inheritance and innovation development of traditional Chinese medicine(TCM).It emphasizes strengthening innovation in TCM research and development(R&D),focusing on major chronic diseases,refractory disorders,emerging infectious diseases,and environmentally associated conditions,to accelerate the launch of innovative TCM drugs with outstanding clinical efficacy and distinct therapeutic advantages.This article systematically analyzed the innovative TCM drugs approved since the enactment of the Drug Registration Regulation in 2020,aiming to serve as a medication reference for clinicians and promote the clinical use of innovative TCM drugs.Our multidimensional analysis included the quantity and registration categories of approved drugs,composition of ingredients in TCM preparations,routes of administration and dosage forms,therapeutic functions and indications,evidence supporting market approval,as well as the review and approval procedures.The finding revealed that with the implementation of policies supporting the inheritance and innovation of TCM,deeper regulatory science research,continuous enhancement of evaluation standards system including efficacy assessment methods and quality control,and ongoing optimization of the review and approval mechanisms,the R&D of innovative TCM drugs is increasingly prioritizing clinical value-oriented paradigm.Greater emphasis is placed on leveraging human experience as evidence to support R&D decisions and regulatory submissions.Consequently,more high-quality innovative TCM drugs with significant clinical value are anticipated to enter the market,better meeting public medication needs.

Abstract:Objective:To explore the mechanism of action of IgD-Fc-Ig fusion protein on a human rheumatoid cell model,which involves co-culturing FcδR high/low expressing Jurkat cells(Jurkat-WT,Jurkat-FcδR+,Jurkat-FcδR+/-)with MH7A cells following immunoglobulin D(IgD)stimulation.Methods:In vitro experiments were set up with a blank control group,an IgD group,and an IgD-Fc-Ig treatment group.The effects of IgD-Fc-Ig on the proliferation of MH7A cells in the human rheumatoid cell model were observed using CCK-8 cell viability assay kit and EDU-488 cell proliferation assay kit.The impact of IgD-Fc-Ig on the invasion and migration of MH7A cells in the human rheumatoid cell model was assessed using Transwell chambers.Results:In the human rheumatoid cell model,Jurkat-FcδR+cells exhibited stronger promotion of proliferation,migration,and invasion of MH7A cells compared to Jurkat-WT and Jurkat-FcδR+/-cells.IgD-Fc-Ig was found to inhibit the proliferation,migration,and invasion effects of Jurkat-WT and Jurkat-Fc8R+cells on MH7A cells in the human rheumatoid cell model.Conclusion:IgD-Fc-Ig can target high levels of Fc8R,thereby inhibiting the abnormal activation of fibroblast-like synoviocytes and the cartilage-destructive effects induced by IgD-stimulated T cells.

Abstract:Chikungunya fever(CHIKF)is a mosquito-borne infectious disease caused by the Chikungunya virus(CHIKV).It is primarily characterized by clinical manifestations such as fever,arthralgia and rash.Although the fatality rate is relatively low,it can lead to chronic arthritis and persistent joint dysfunction,significantly impacting patients' quality of life.Currently,there are no specific antiviral drugs available,and clinical management mainly focuses on symptomatic and supportive care.In recent years,advances in virological and molecular biology research have gradually elucidated the life cycle and pathogenic mechanisms of CHIKV,providing new targets for drug development.This article systematically reviews the virological characteristics,epidemiological features,and clinical manifestations of CHIKV,with a focus on summarizing recent progress in the development of small-molecule inhibitors targeting viral entry,replication,and assembly.Additionally,the mechanisms of action and potential applications of these inhibitors are discussed.

Abstract:Modern research reports that betel nut contains a variety of chemical components,including alkaloids,polyphenols,flavonoids,terpenes,etc.,which has antioxidant,anti-inflammatory,antibacterial,anti-tumor,protection of gastrointestinal mucosa,expelling worms,anti-platelet,anti-atherosclerosis,improving osteoporosis,anti-depression and anti-fatigue,regulating endocrine function,regulating intraocular pressure,anti-viral and other effects.Some of these effects have a positive role in the prevention and treatment of related clinical diseases.However,it has certain toxicity to the reproductive system,urinary system,liver,heart,and oral mucosa.In order to fully develop and utilize betel nut,a review of its chemical components and pharmacological effects is presented,with the aim of providing references for the modernization research of betel nut and providing basis for its application in clinic.

Abstract:This paper systematically reviews 156 US FDA Complete Response Letters(CRLs)for chemical drugs,summarizing issues identified in areas such as control of drug substances and excipients,product development,and quality research.From a pharmaceutical review perspective,it elaborates and analyzes the key and commonly overlooked issues.The publicly available CRLs contain numerous reference-worthy questions and constructive recommendations related to review.The analysis reveals that the FDA's review principles and standards are highly consistent with those of China,further demonstrating that China's regulatory capacity has reached a high level since the reforming of the review and approval system.This progress provides solid backing for China's transition from a major manufacturer to an innovator in the global pharmaceutical industry.

Abstract:With the rapid development of the biologics industry,therapeutic recombinant biologics have become increasingly prominent in disease treatment.As an integral part of pharmaceuticals,packaging systems play a crucial role in ensuring the safety,efficacy,and quality stability of drugs.However,during the actual review process,it has been found that there are still many common issues in research related to packaging systems that may affect drug quality and patient medication safety.This article summarizes common issues of packaging systems of therapeutic recombinant biologics in the marketing application,including the joint review of drug-device combination products,compatibility,and sealing,based on relevant domestic and international regulatory guidelines and review practices,and provides an in-depth analysis of review concerns,with the aim of helping applicants improve the quality of application materials.

Abstract:Antibody-drug conjugate(ADC)are targeted therapeutics composed of monoclonal antibodies chemically linked to small-molecule payloads via specialized linkers.In recent years,ADC development has grown rapidly,with more than a dozen products approved globally.With advancing technologies,next-generation ADC are evolving toward increasingly complex designs,such as dual-payload ADC,which conjugate two distinct payloads to a single antibody molecule.Dual-payload ADC are expected to enhance anti-tumor efficacy by delivering two active agents simultaneously,thereby improving the killing of heterogeneous tumor cell populations and overcoming drug resistance.However,their structural complexity and increased challenges in controlling product homogeneity and impurity levels pose new difficulties for pharmaceutical development and regulatory evaluation.This article discusses the key considerations in the development and pharmaceutical review of dual-payload ADC,including raw material selection,manufacturing processes,structural characterization,impurity profiling,analytical methodology,quality control,and stability assessment.Based on issues observed in actual regulatory submissions,the paper highlights pharmaceutical development trends and review challenges specific to dual-payload ADC,aiming to provide practical references for their development and quality research.

Abstract:Elemental impurities in recombinant protein products,as significant process-related impurities,play a pivotal role in product safety and quality attributes.The 2025 edition of the Chinese Pharmacopoeia with ICH Q3D(R2):Elemental Impurities,provides crucial guidance for controlling elemental impurities in recombinant protein products.By summarizing and analyzing the relevant requirements of current regulations,combined with considerations on the specific challenges for recombinant protein products,this paper aims to establish a risk-based,comprehensive impurity control strategy throughout the entire process for drug developers'reference.

Abstract:Technical advancements have led to greater diversity in the molecular entities of innovative recombinant monoclonal antibodies,enabling them to better meet clinical needs.A growing number of innovative monoclonal antibody products are being submitted for market approval through accelerated regulatory pathways due to their remarkable clinical efficacy.To address the challenges in chemistry,manufacturing,and controls(CMC)development during rapid drug advancement,it is necessary to introduce scientific regulatory tools.This article summarizes the definitions of platform knowledge provided by various domestic and international regulatory agencies,as well as regulations regarding the use of platform knowledge to support CMC development in accelerated programs.It also analyzes the benefits and challenges of applying platform knowledge based on the actual conditions,with the aim of providing actionable recommendations for the future use of this regulatory tool in China.

Abstract:Objective:To summarize and analyze the clinical features,diagnosis,treatment and prognosis of patients with myositis,myocarditis and myasthenia gravis overlap syndrome caused by immune checkpoint inhibitors,in order to provide a reference for the diagnosis and treatment of this adverse reaction.Methods:The clinical data of four patients with overlap syndrome of myositis,myocarditis and myasthenia gravis caused by immune checkpoint inhibitors admitted to our hospital from January 2023 to June 2024 were collected,and the characteristics,clinical manifestations,auxiliary examination results,treatment methods,and outcomes were analyzed and summarized.Results:Among the four patients,three were female and one was male,and the ages at diagnosis were 56～69 years.The syndrome appeared immediately after receiving PD-1 inhibitors or PD-1/CTLA-4 bispecial antibodies for the first course,and the median time was 16.5 days.The main clinical symptoms were fatigue,myalgia,drooping eyelids,restricted mouth opening,and impaired speech.The ECG showed sinus hyperrhythmia with different degree of conduction block.All the four patients received high doses of glucocorticoids and brompyristine,and three of them were treated with gammaglobulin,one was treated with tofaciib simultaneously,the other was treated with plasma exchange and morpheolate,and one patient had a temporary pacemaker placed.All the four patients were discharged from hospital after significant improvement of symptoms,and ICls therapy was not restarted.Conclusion:Myositis,myocarditis,and myasthenia gravis overlap syndrome are serious adverse reactions of ICIs treatment.High-dose glucocorticoids are still the primary treatment,and early combination of immunoglobulin may be beneficial for symptom improvement.Early diagnosis through multidisciplinary cooperation model and necessary life support may provide a good prognosis.

Abstract:Objective:To provide suggestions and thoughts for optimizing the whole process information management of biological samples in phase I clinical trials.Methods:Based on Vue framework,ClickOnce technology,Golang programming language,My SQL database as technical support,combined with the requirements of biological sample management in phase I clinical trials,an information management system for biological samples including the functional modules of user management,configuration,equipment management,collection management,processing management,inventory management of biological samples,as well as query and export functions was established.Results:The information management system for biological samples facilitates the whole process management of samples by utilizing unique identification barcodes assigned to each sample,so that the records of sample are clear,which can enhance the efficiency of biological sample management,reduce the protocol deviation,and ensure the accuracy of the samples.Conclusion:The application of information technology in the management of biological samples in phase I clinical trials realizes the automation and real-time of data collection,ensures the integrality,authenticity,and traceability of sample data,and contributes to improve the quality of phase I clinical trials.

Abstract:Objective:To conduct a comprehensive clinical evaluation of drugs for acute ischemic stroke(AIS)such as butylphthalide,edaravone,uricilin,and edaravone borneol to clarify their clinical application values.Methods:This study evaluated the aforementioned drugs from five dimensions:efficacy,safety,cost-effectiveness,accessibility,and appropriateness,based on literature and publicly available data.Results:There were no significant differences in efficacy and safety among the evaluated drugs.However,butylphthalide showed a relatively higher probability of superiority in the surface under the cumulative ranking curve(SUCRA)ranking.Additionally,it performed better in terms of use convenience,medical insurance coverage,and patient cost burden,resulting in good comprehensive suitability.Clinicians can make selections based on patients'specific needs.Conclusion:Butylphthalide has better comprehensive clinical value in the treatment of acute ischemic stroke,especially in terms of cost-effectiveness and appropriateness.This study can provide a reference for the formulation of relevant drug policies and clinical medication decisions.

Abstract:China's innovative drug development is now in a phase of rapid ascendance.Within this dynamic ecosystem,risk-sharing agreement have emerged as a pivotal policy instrument that enables multi-stakeholder collaboration-governments,commercial payers,and biopharmaceutical companies——to jointly tackle the multifaceted challenges posed by clinical efficacy uncertainties,exorbitant R&D costs,and reimbursement pressures inherent in novel drug development.This study conducted a comprehensive analysis of South Korea's pharmaceutical risk-sharing agreement policy through five key dimensions:scope of application,typological classification,refund guarantee mechanisms,operational procedures,and implementation effectiveness.Based on the research findings,the following recommendations were proposed:exploring the scope of application starting with special drugs,developing diversified typologies of risk-sharing agreements,and implementing safeguards for the risk-sharing agreement process.These policy recommendations seek to further refine China's innovative drug policies.

Abstract:Dulaglutide,a long-acting GLP-1 receptor agonist,has become one of the hotspots in the field of biosimilar drugs.However,as a fusion protein,its inherent structural instability poses a challenge.Modifications or degradation of its GLP-1 functional domain can significantly impact biological activity,making the assessment of pharmaceutical similarity particularly difficult.This article summarizes recent advances,by integrating foreign assessment reports,scientific literature,and regulatory review experiences,outlines fundamental considerations for its pharmaceutical development and evaluation,aiming to facilitate the development of such products.

Abstract:Drug quality standards are the criteria for measuring the intrinsic quality attributes of pharma-ceuticals.They represent the final outcomes and legal embodiment of drug efficacy,safety,and quality control,spanning the entire lifecycle of drug development.The purpose of drug quality standards is to provide patients with consistent inter-batch drug quality,ensure controllable drug quality,and thereby guarantee the safety and efficacy of medications for patients.In the development of blood products derived from human blood,specific human immunoglobulin products possess unique pharmacological characteristics,and their production processes and quality control can fully leverage the mature systems established for conventional human immunoglobulins.At the current stage,specific human immunoglobulin products in China demonstrate significant market development potential.This article systematically reviewed the quality standards for specific immunoglobulin products included in the Chinese Pharmacopoeia 2025 edition,compares them with corresponding varieties in the European Pharmacopoeia and the United States Pharmacopoeia,and elaborates on the key technical requirements involved in relevant quality control items,taking into account the current state of research and development of specific human immunoglobulin in China.

Abstract:With the aging of population and increasing burden of chronic diseases,the development of regenerative medicine research has accelerated.Cell therapy medicinal products(CTMP),after a long-term development and gradual maturation process,have become an important branch of regenerative medicine research.This article mainly introduces the regulatory frameworks for regenerative medicine therapeutic drugs in major regulatory agencies around the world,as well as the pharmaceutical technical requirements for CTMP in China.It also brings thoughts and prospects on the pharmaceutical technical requirements for other cell-based regenerative medicine therapeutic drugs,with the aim of effectively promoting and accelerating the innovative and high-quality development of such drugs.

Abstract:This paper aims to introduce the requirements for the content and technical aspects of the application materials for re-registration of biological products based on the current regulations and policies.It mainly includes the production,sales and inspection qualification situations over the past five years,the remaining pharmaceutical issues in the past registration approval documents or registration approval notices,and the changes in raw materials,production processes,quality standards,etc.The approved instructions,labels,actual samples,and other information are explained and analyzed.Based on the past review results and the problems existing in the application materials,certain explanations and introductions are provided regarding the content and technical requirements for the application materials.

Abstract:Recombinant protein vaccines have become a pivotal tool in the infectious disease prevention and control system,owing to their distinct safety advantages,favorable stability,and potential for large-scale production.This article systematically reviewed the entire technological chain of recombinant protein vaccines,focusing on key advances in rational antigen design,the application of expression systems,and adjuvant development.Through analysis of vaccine cases targeting respiratory syncytial virus,SARS-CoV-2,and herpes zoster,the study elucidates how antigen structural design,adjuvant innovation,and integration of technological platforms synergistically drive the more scientific and efficient development of recombinant protein vaccines.Furthermore,the article explores cutting-edge research directions,including AI-assisted antigen screening and design,broad-spectrum vaccines,mucosal immunization vaccines,and regulatory science pathways based on platform technologies.Looking ahead,recombinant protein vaccine technology,through interdisciplinary integration,will continue to play a central role in enhancing vaccine efficacy and improving response speed to emerging and re-emerging infectious diseases.