Analysis on approval and declaration of new Chinese medicines from 2016 to 2022 / 国际中医中药杂志

Objective:To discuss and analyze the current situation of the application and approval of new Chinese medicine in China; To provide a reference for the research and development of new Chinese medicines in the future.Methods:The drug registration data were retrieved from Xanda database from January 1, 2016 to December 31, 2022, and the information of new approval and application of new Chinese medicines during this periods was systematically organized from the aspects of the number of registered varieties, registration categories, therapeutic areas, prescription sources, dosage form distribution, development cycle, clinical research and control drugs.Results:From 2016 to 2022, the total number of application for new Chinese medicines was 265. The number of registration classification 1.1 of new compound drugs was the largest. The dosage forms of new drugs were mainly granules, capsules, and tablets. Indications mainly focused on respiratory, neuropsychiatric, digestion and cardio-cerebrovascular diseases, etc. From 2016 to 2022, the total number of approval for new Chinese medicines was 29, of these, 19 from 2021 to 2022. The number of registration classification 1.1 of new Chinese medicines was the largest. The treatment fields are mainly respiratory system, gynecology and neuropsychiatric diseases, etc. The dosage forms of new drugs were mainly granules, capsules, and tablets. The number of drugs in prescriptions was 6-15. High-frequency drugs included Glycyrrhizae Radix et Rhizoma, Ephedrae Herba, Scutellariae Radix, Pinelliae Rhizoma, Poria and Gypsum Fibrosum. Phase Ⅱ and phase Ⅲ of the clinical trials had the largest number. The development period was approximately between 10-20 years. The most prescription source of new drugs was clinical experienced prescriptions and hospital pharmaceutics.Conclusion:The results show that China has been gradually building-up a relatively complete ecosystem for research and development of new Chinese medicines, helping to develop more high-quality Chinese medicines.

Current registration status and pharmaceutical review considerations of bispecific antibody drug in China / 中国生物制品学杂志

@#In recent years,domestic and foreign bispecific antibody(BsAb,referred to as bis-antibody)has been developing rapidly,and as of December 2023,nearly 200 bis-antibodies have been in clinical research,and more than a dozen bisantibody drugs have been approved for marketing. This paper reviews the domestic and foreign registration status of bis-antibody,and discusses the common technical problems in the pharmaceutical development of such products in combination with the experience of pharmaceutical review and related literature,in order to provide a basis for the pharmaceutical development and evaluation of bis-antibody drugs.

Effectiveness of Different Concentrations of Chlorhexidine and Metronidazole Gels in the Management of Gingivitis: A Randomized Clinical Trial

Background: Management of gingivitis is commonly done by the removal of etiological agents by Periodontist. However, use of topical applications of antibiotic combinations has been shown to improve the treatment outcome. Various drugs alone or in combination have been used. So this study was conducted to determine the effect of different concentrations of combination drugs on gingivitis.Material & Methods:100 patients of gingivitis were divided into two groups of 50 each – Group-A and Group-B. After scaling and root planing, Group-A patients were made to apply Metronidazole 1% and Chlorhexidine 0.25% for period of 12 weeks while as Group-B patients applied Metronidazole 1.5% and Chlorhexidine 0.50% for 12 weeks. Baseline scores of gingival index and bleeding index were recorded followed by readings at 4 and 12 weeks.Results:Results showed that there was a significant improvement in gingivitis and bleeding on probing at 4 and 12 weeks after local application of Metronidazole and Chlorhexidine gel in both the groups. However there were no statistically significant differences between two groups.Conclusions:Topical application of Metronidazole and Chlorhexidine gel as an adjunct to scaling and root planing is an effective treatment modality for the management of gingivitis and the concentrations of the combination do not have any significant effect on the treatment.

Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported / 中华肿瘤杂志

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

Guidelines investigation and technical considerations of virus safety during investigational new drug application of innovative monoclonal antibody products / 药学学报

With the development of antibody manufacturing technology and improvement of new drug research in domestic industry, more innovative monoclonal antibody products submitted investigational new drug (IND) application. At the same time, monoclonal antibody products from abroad which have been approved marketing authorization and/or conducted clinical trials submitted IND applications in China. The National Medical Products Administration (NMPA) issued the "Guideline of Investigational New Drug Application" (No. 16, 2018) which emphasized the chemical, manufacturing, and control (CMC) regulatory, and dossier requirements in IND application, greatly promoted the application quality of innovative biological products. However, compared to the Food and Drug Administration (FDA) and European Medicines Agency (EMA), our particular guidelines are insufficient, such as guideline on virus safety evaluation of biotechnological investigational medicinal products. This review investigated the questions raised by sponsors from 2018 to 2020, including the end of production cell (EOPC) and/or unprocessed bulk (UPB) testing and virus removal or inactivation validation. Meanwhile, sponsors submitted different dossiers due to differences in understanding of stage requirements of guidelines from domestic and abroad. Based on the guidelines of virus safety from NMPA, FDA, and EMA, and the technical considerations, this review puts forward personal suggestions on the adventitious agents testing and virus removal or inactivation validation in manufacturing process, aim to ensure virus safety of innovative monoclonal antibody products in clinical trials.

Basic research of fibrosis on atherosclerotic plaque stability and related drug application / 中国中药杂志

In the background of the high incidence and high mortality of cardiovascular diseases,atherosclerosis is the main pathological feature of cardiovascular diseases and the core pathological basis for disease progression. In the evolution of atherosclerotic plaques,the rupture of unstable plaques,plaque shedding and formation of thrombosis are the most dangerous parts. In this process,the formation of plaque fibrosis is the core mechanism regulating plaque stability. Additionally,fibrosis reflects dynamic changes in the inflammatory processes and pathological changes. In view of the inflammation regulation and fibrosis regulation,this paper clarified the process of atherosclerotic plaque,explained the roles of relevant inflammatory cells and cytokines in plaque stability,and summed up drug researches related with stable plaque in recent years. In the future,improving the fibrosis will be a new idea for stabilizing plaque in atherosclerosis drug development.

Considerations for anti-cancer drug application by single arm trials / 中华肿瘤杂志

Single arm trial (SAT) was widely used for new drug application (NDA) of novel anti-cancer drugs in recent years. The listing time was greatly shortened by SAT while comparing with randomized controlled trials (RCT). Thus, the companies intended to get NDA through SAT. To encourage innovation and accelerate the developments of anti-cancer agents, we summarize the background and key issues of SAT, discuss the conditions of accepting SAT for NDA, and systematically elaborate the design and principles of SAT in this review.

Regulation and new drug application of botanical drugs in the world / 中国药理学与毒理学杂志

This review summarizes the developmental history of natural products and research status of botanical products in different oversea countries. This paper outlines the regulation for new drug application of botanical drugs from the USA, European Union, and Japan. It also uses the Vergen (the first botanical drug approved by US FDA) as an example to discuss how to meet regulatory require-ments for new drug applications.

Research on Mechanism of Drug Clinical Hold in USA / 中国药学杂志

OBJECTIVE: To analyze the mechanism of clinical hold in USA and to provide reference and enlightenment for clinical trial review process reform in China. METHODS: Analyzed the regulation, review process, reasons and impacts of drug clinical hold in USA and compared with clinical trial system in China, then provided advice for our country. RESULTS AND CONCLUSION: FDA review IND by implied license process within only 30 d, and may permit the clinical trials begin as early as possible, the clinical trial could be imposed on hold, and the hold could also be lifted or transfer into inactive status, thus protect the health and rights of subjects to the largest extent, and in the same time improved the review efficiency. It is necessary and feasible that clinical hold is introduced into clinical trial system in our country.

Research progress of drugs that can control and prevent age-related cataract / 国际眼科杂志(Guoji Yanke Zazhi)

@#The lens is a transparent tissue without vessel, which is mainly composed of a layer of epithelium cells and differentiating fiber cells. With aging, lens opacity can deteriorate vision significantly and even result in blindness, which is termed as age-related cataract(ARC). A fully developed treatment method of ARC is surgery, while a few cataracts in the initial stage can be suppressed via drugs efficiently.This paper introduced relevant drugs and important ingredients that can suppress and prevent ARC, and then summarizes clinical applications and existing researches with respect to drug treatments in the process of cataract suppression and treatment.

Pharmaceutical Care for One Child with Kawasaki Disease Suspected of Bacterial Meningitis / 中国药师

Objective: To discuss the rational drug application of Kawasaki disease in children with upper respiratory tract infection in order to provide reference for the therapy of Kawasaki disease suspected of bacterial meningitis.Methods: The medical record of a 2-year-old boy with Kawasaki disease was retrospectively analyzed, and the anti-infection treatment was analyzed and evaluated.Meanwhile, the mechanism of elevated leukocyte count in cerebrospinal fluid (CSF)of children with incomplete Kawasaki disease was discussed.The pharmaceutical care and treatment results in the diagnosis and treatment process were analyzed as well.Results: The anti-infective therapy in early stage was reasonable as the early symptoms of respiratory tract infection in the child were obvious, however, the choice of aztreonam was defective.On the premise of the clinical diagnosis of Kawasaki disease and excluding bacterial meningitis, the medication was timely adjusted.Finally, the symptoms of the child were improved.Conclusion: The application of anti-infection drugs should be reasonable in clinics, and the abnormality in cerebrospinal fluid should be paid more attention in children with Kawasaki disease.It is necessary to strengthen clinical observation and pharmaceutical care in order to guarantee the safety of medication for patients.

Botanical Drug Development-Guidance for Industry and Expert Views on Botanical Drug Development in the US / 世界科学技术-中医药现代化

The definition of new drugs in China and the US has no major differences on chemical drugs and biologics.However,Chinese medicines,which are regulated as over-the-counter (OTC) or prescription drugs in China,are mostly regulated as food and/or dietary supplements without FDA approved medicinal use for marketing.The FDA Guidance for Industry-Botanical Drug Products (2004) and the recently revised Guidance for Botanical Drug Development (2016) paved the way for Chinese herbal medicine and other botanical mixtures to be further developed as new drugs through clinical trials and other nonclinical studies.FDA recognizes the value of traditional medicines as part of the previous human experiences to support the safety and speed up early phase clinical trials of botanical products under investigational new drug (INDs) applications.The revised Guidance included addition recommendations for late phase development,like phase 2 trials and new drug applications (NDA),to resolve some of the unique challenges on batch-tobatch consistency (e.g.,a totality of evidence approach,including raw material control,bioassays,multiple-batch and multiple-dose clinical trials,and etc.).The approval of Veregen and Fulyzaq (now Mytesi) are new molecular entity / new chemical entity type of new drugs,treasured fruits from several hundred INDs studying botanicals.With those NDA examples,it is expected that further study of Chinese herbal medicines as new botanical drugs through further clinical and nonclinical development will be fruitful.On the other hand,long-term commitments are universal for new drug development.And it will also be true for bringing Chinese herbal medicines as botanical new drugs to international markets.It still takes time to see whether artesunate tablets can be verified through further clinical trials and achieve the same level of Coartem.

Analysis of FDA's Review for NDA208542-Rociletinib / 世界科学技术-中医药现代化

Lung cancer is the highest mortality rate of malignancies in the world.Among them,non-small cell lung cancer (NSCLC) accounts for 85％.Epidermal growth factor receptor (EGFR) gene is one of the most common driving genes in NSCLC.The EGFR tyrosine kinase inhibitors (EGFR-TKIs) bring a breakthrough in the treatment for patients with EGFR gene-sensitive mutations.However,the drug resistance problem of EGFR-TKIs has been increasingly highlighted.So a drug for the patients accompanied by EGFR T790M positive mutation and along with progression in or after treatment with EGFR-TKI NSCLC is clinically urgent needed.Rociletinib is designed to address this unmet clinical need.While considering the non-superior effectiveness to the similar drugs in the market and the high risk of safety (hyperglycemia,QT prolongation and sudden death) of Rociletinib,the dosage was not accepted by the Food and Drug Administration (FDA).And Rociletinib did not make it to the market eventually.This paper discussed lessons learned from this case under review perspective for reference and inspiration.

Chronic lymphocytic leukemia: a clinical review including Korean cohorts

Only 5th decade ago, chronic lymphocytic leukemia (CLL) was only recognized as disease group of presenting features like peripheral lymphocytosis, organomegaly including of splenomegaly. As understanding of disease biology and molecular diagnostic tools are getting improved gradually, characterization of variation in CLL's clinical courses was facilitated, resulting in better risk stratification and targeted treatments. Consequently multiple new targeted agents have been used in treatment of CLL, it makes improved clinical outcome. Rituximab containing chemoimmunotherapy (combination of rituximab, fludarabine, and cyclophosphamide) have shown better overall response rate and progression-free survival on fit patients' group in front-line setting, result in standard first-line therapeutic option for CLL. Furthermore, after introducing that the B-cell receptor is crucial for the evolution and progression of CLL, emerging treatments targeting highly activated surface antigens and oncogenic signaling pathways have been associated with several successes in recent decades. These include new anti-CD 20 monoclonal antibody (obinutuzumab), the bruton tyrosine kinase inhibitor (ibrutinib), the phosphatidylinositol 3-kinase inhibitor (idelalisib), and B-cell CLL/lymphoma 2 inhibitor (ABT-199 and ABT-263). So, we discuss not only general pathophysiology of CLL, but also rapidly advancing treatment strategies that are being studied or approved for treatment of CLL.

Analysis of Pathogens Distribution and Antibiotics Use in 93 Cases of Bronchiolitis Child / 中国药房

OBJECTIVE:To provide reference for antibiotics use. METHODS:A retrospective study was conducted to analyze the detection of pathogens and antibiotics use in 93 children with bronchiolitis in our hospital between Jan. 2013 to Dec. 2014. Pathogens detection mainly included respiratory virus,pneumonia mycoplasma IgM antibody and pneumonia chlamydia IgM anti-body and sputum culture. RESULTS:Among 93 cases,22 cases (23.66%) were positive in respiratory virus IgM antibody test, mainly for respiratory syncytial virus;17 cases(18.28%)were positive in sputum culture test,mainly for the Moraxella catarrha-lis,Haemophilus influenza and Streptococcus pneumonia;10 cases(10.75%)were positive in Atypical pathogens test,mainly for mycoplasma pneumonia. There were 47 cases(50.54%)of antibiotics;Among them,only 12.77%(6/47)had clear indications for using antibiotics;the children who were 1-3 months old had the highest percentage of antibiotics,accounting for 81.82% at the same age;the duration of disease was significantly prolonged in the cases who used antibiotics,with average duration of(8.27± 3.32) d. CONCLUSIONS:Bronchiolitis is still usually caused by virus infection in our hospital,the ratio of antibiotics use are high and most of them don't have bacterial infection indications.

Analysis of Rationality of Solvents and Indications for Using TCM Injections in Our Hospital / 中国药房

OBJECTIVE:To provide reference for the rational use of TCM injections. METHODS:The related data of using TCM injections was drawn from May 2009 to May 2014. And the data of 5 TCM injections,including Shengmai and Shenmai in-jection,were statistically analyzed,the indications of 8 TCM injections,including Shengmai and Shenmai injection,were also sta-tistically analyzed. RESULTS:In solvents evaluation,the 5 TCM injections were used 501 times,in which 391 times(78.04%)of the solvents used were rational,381 times(76.05%)of the solvent doses used were rational;in clinical indications evaluation,the 8 TCM injections were used for 2 579 patients,in which 1 120 cases were in accordance with the instructions while the other 1 459 cases were not,the qualification ratio was 43.43%. CONCLUSIONS:There were still some problems in using TCM injection in our hospital in the aspects of solvent as well as indications.

Analysis of Clinical Application of Vancomycin in Our Hospital from 2013 to 2014 / 中国药房

OBJECTIVE:To provide reference for further formulation of the rational use of vancomycin. METHODS:Retro-spective analysis was conducted on the related information of discharged patients who intravenously used vancomycin from Jun. 2013 to Dec. 2014. RESULTS:178 patients were enrolled,with average age of 59.6 and 73.60% male,who were mainly with lung infectious(74.72%). Support examinations were sufficient before using of vancomycin. 66.29% patients were empirically giv-en vancomycin with pathogenic detection rate of 85.39%. 71.91% patients were conducted therapeutic drug monitoring with only 47.54% of first blood samples achieved the target range. CONCLUSIONS:Vancomycin application is generally rational in our hos-pital. However,issues like duration of empirical therapy,rational therapeutic monitoring,and individualized start dosing still need to be noticed.

Analysis of Antidepressants Consumption in 34 Hospitals of Wuhan During 2011-2013 / 医药导报

Objective To provide basis for rational drug use of clinical practice by analysis of antidepressants application in Wuhan. Methods Antidepressants were classified according to the structure and mechanism. By using the analytical method of the defined daily dose (DDD) recommended by WHO,authors statistically analyzed the relative data of antidepressants used in 34 hospitals of Wuhan from 2011 to 2013. Results The consumption of the antidepressants had been increased year by year,selective serotonin reuptake inhibitor (SSRIs) and serotonin noradrenergic reuptake inhibitors (SNaRIs) were widely used and presented higher proportion than others in the consumption of antidepressants,the average amount of the sales was 50.49% and 21.81%,respectively.The application of tricyclic antidepressant (TCAs) decreased in Wuhan,the amount of sales for 3 years accounted for 0.56%,0.37% and 0.15%. Conclusion SSRIs and SNaRIs have already become the first-choice drugs in clinic practice because of good efficacy and high safety,other new types of antidepressants have a great potential for development,TCAs are fewly used now.

Utilization of Kanglaite Injections in Lung Cancer Patients in 11 Hospitals of Zhejiang from 2009 to 2013 / 中国药师

Objective:To evaluate the utilization of Kanglaite injections in lung cancer patients in 11 hospitals of Zhejiang and analyze the prescription data. Methods: Totally 40-day prescription data of the patients with lung cancer in 11 hospitals of Zhejiang were withdrawn every year from 2009 to 2013. The data in respect of the consumption sum, DDDs, department distribution and medical insurance category of Kanglaite injections were analyzed. Results: The consumption sum of Kanglaite injections used in the patients with lung cancer in 11 hospitals of Zhejiang showed an upward trend year by year, the growth in 2011 and 2012 was the fastest, and the sum in 2012 was 1. 77-fold of that in 2009. The consumption sum proportion of Kanglaite injections in total amount of drug consumption rose after the first drop. The top 3 departments were oncology, radiotherapy and thoracic surgery in the five years. The dosage and DDDs of Kanglaite injections were also in an increase trend year by year, and the growth in 2011 and 2012 was the fastest. Conclusion:The utilization of Kanglaite injections in the patients with lung cancer in Zhejiang area shows a continuous rapid growth momentum, therefore, it is still essential to strengthen the reasonable application in clinics.