ArchiveTo provide suggestions for the improvement of China's drug priority review and approval system.
Japan's pioneer designation system was analyzed through literature survey compared with China's drug priority review and approval situation.
The Japanese pioneer designation system has facilitated the research and development of new drugs in Japan, accelerated the speed of new drug launches, and allowed Japan to extensively participate in international multicenter clinical trials.
China should actively participate in international multicenter clinical trials, designate specialized personnel to fully manage the marketing application process and promote the synergy of multiple priority review and approval mechanisms.
The health decision will be impacted by the selection of different comparators that influence the results of the comparative effectiveness and incremental cost-effectiveness analysis. With the application of health technology assessment in assistent of health decision-making, the selection of comparators has gradually received stakeholders' attention. Focusing on the comparators selection, this study systematically reviews the health technology assessment guidelines and comparator selection guidelines published by seven countries and regions including China Taiwan, Japan, the United Kingdom, Germany, Canada, Australia, the United States and international organizations based on a literature review. Meanwhile, taking the selection of comparators as an example in the health technology evaluation report of chimeric antigen receptor T-cell (CAR-T) immunotherapy therapies when applying for medical insurance access in different countries, the international experience is summarized from the selection process, criteria, methods, usage and other dimensions. To deal with the current issues discussed in this study, the decision-making departments and stakeholders need to determine the comparators before the beginning of the evaluation, establish a two-way communication and feedback mechanism, determine the selection criteria and methods based on different decision-making purposes and uses, and select flexible response options for special circumstances, so as to provide reference for optimizing the selection of comparators in drug value evaluation.
Since the first anti-monopoly review case was completed, public authorities are starting to pay more attention to reverse payment settlement agreements. However, it is extremely problematic for any single mode of analysis to accurately identify the illegality of reverse payment settlement agreements, not excluding the rule of reason. On the contrary, the hybrid modes of analysis applied by the Supreme Court in this case is both flexible and definitive, which is expected to become a new paradigm in China. In view of this, this article analyzes the trial thinking of the Supreme Court, and summarizes the difficulties of the case in terms of the effect analysis, validity review and exemption clause. Finally, based on the characteristics of reverse payment settlement agreements and the antitrust rules in intellectual property field of China, this article makes suggestions to improve the mode of analysis.
Lazertinib is a highly effective, oral and irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI). On January 18, 2021, the Korea Ministry of Food and Drug Safety (MFDS) first approved lazertinib for the treatment of patients with EGFR T790M mutation-positive locally advanced or metastatic non-small cell lung cancer, who previously received EGFR-TKI treatment. This article introduces lazertinib's mechanism of action, pharmacokinetics, pharmacodynamics, clinical research, safety evaluation, etc.
Visible particulates in injectable products directly jeopardize patient safety, and it is a critical quality attributes of injectable products. In recent years, unqualified products and recall events related to injectable products caused by visible particulates occurred frequently. Therefore, it is necessary to conduct the risk assessment, production process control and product detection of visible particulates in injectable products. Referring to the U.S. FDA Inspection of Injectable Products for Visible Particulates Guidance for Industry (draft guidance) and relevant guidelines and manufacturing and controls (CMC) review experience, this article mainly introduces and discusses the ideas of visible particulate control in chemical injections from the aspects like concept of visible particulates, quality risk assessment, production process and sample inspection control, life cycle management, etc., hoping to provide reference for the control and evaluation of visible particulates in injections.
To compare the in vitro dissolution profiles of quetiapine fumarate tablets from different sources, in order to provide reference for the evaluation of quality consistency.
The solvents used in this study were 0.01 mol·L-1 hydrochloric acid, 0.1 mol·L-1 hydrochloric acid, pH 4.5 acetate buffer, pH 6.8 phosphate buffer and water, respectively, with the volume of 900 mL. The paddle method was applied at the rotation speed of 50 r·min-1. The content of quetiapine fumarate was determined by HPLC. The cumulative dissolution was calculated and the dissolution curves were obtained. Similarity factor (f2) method was used to evaluate the similarity of dissolution profiles.
Among the reference preparations from 5 different sources, the cumulative dissolutions in 15 min were all above 85% or the similarity factors (f2) greater than 50. The dissolution curves were similar and the dissolution behaviors were consistent. Among the domestic generic preparations from 5 different sources, product from manufacturer B in 0.1 mol·L-1 hydrochloric acid, products of 100 mg and 200 mg from manufacturer A in pH 6.8 phosphate buffer, the f2 were less than 50, which are not similar to the reference. The other batches have similar dissolution profiles to the reference preparations, thus their dissolution behavior are consistent.
The dissolution profiles of reference preparations from different sources are similar, and the dissolution behaviors are consistent. However, in a dissolution medium not specified in the pharmacopoeia of quetiapine fumarate tablets, a few domestic generic preparations from different sources have dissimilar dissolution profiles and inconsistent dissolution behaviors. In order to make a comprehensive assessment of the consistency of quetiapine fumarate tablets, the specific bioequivalence experiments and other indicators of pharmacy still needs to be integrated for the reference and domestic generic preparations from different sources.
Corydalis saxicola Bunting mainly distributes in Guangxi, Guizhou and Yunnan, etc., and it is a genuine folk medicine in Guangxi Province. The chemical composition of Corydalis saxicola Bunting mainly contains alkaloids, flavonoids, steroids and so on. It has activities of liver protection, anti-tumor, and anti-oxidation, thus often used in the treatment of sore boils, hepatitis, liver cirrhosis, and liver cancer. The chemical constituents and pharmacological effects of Corydalis saxicola Bunting are summarized in this article, and the quality markers (Q-Marker) of Corydalis saxicola Bunting were predicted and analyzed based on the concept of quality marker, providing scientific basis for the establishment of quality evaluation system of Corydalis saxicola Bunting and reference for the development of its medicinal value.
In recent years, the use of N-acetylgalactosamine (GalNAc) conjugates to target asialoglycoprotein receptors and further deliver oligonucleotides to hepatocytes has become a breakthrough approach in the field of therapeutic oligonucleotides. Compared with traditional delivery methods of nucleic acid drugs, GalNAc-nucleic acid conjugation is a simple method of liver delivery. It exhibits liver targeting specificity, high efficiency, high safety, large-scale preparation and many other advantages, thus has research value of in-depth development and broad prospects for clinical application. Givosiran, developed using GalNAc conjugation, has been approved by FDA for the treatment of acute hepatic porphyria, and there are 7 other conjugates are in registration review or phase III clinical trials, and at least 21 GalNAc nucleic acid conjugates are in the early stages of clinical development. However, the relevant research foundation of GalNAc conjugation in China is relatively weak, and no related products are on the market, making it a neck-stuck technology in China. Therefore, this review focuses on GalNAc and its derivatives as nucleic acid drug delivery vehicles and their application progress in small interfering RNA (siRNA) and antisense oligonucleotides (ASO). This review provides reference for the development of domestic GalNAc conjugates.
To introduce the history and regulatory policies of next-generation sequencing companion diagnosis and antitumor drug research and development in the United States in order to provide reference for practitioners in China.
Using literature research, case analysis, and comparative analysis, the challenges faced by China's next-generation sequencing companion diagnostics supervision and enterprise research and development were elaborated from the regulatory guidelines for next-generation sequencing companion diagnostics in the United States and the products approved by the US Food and Drug Administration.
Co-development of next-generation sequencing companion diagnosis and antitumor drugs can help explore and clarify the mechanism of drug action, accurately identify patients, and increase the success rate of antitumor drug development. With the advent of the era of precision medicine, the rapid development of next-generation sequencing technology and the policy of clinical value-oriented anti-tumor drug research and development, China's next-generation sequencing companion diagnosis and anti-tumor drug development are increasingly synchronous. It is necessary to propose corresponding regulatory policies and research and development guidelines to promote the development of next-generation sequencing companion diagnosis.
The antiepileptic drug vigabatrin (VGB) is a selective and irreversible inhibitor of γ-aminobutyric acid transaminase, which can inhibit the abnormal electrical activity in brain via increasing the concentration of inhibitory neurotransmitter γ-aminobutyric acid (GABA). The clinical indications of VGB include infantile spasms and refractory partial seizure epilepsy, acting as a single treatment or an adjuvant treatment, respectively. Visual field loss is the main adverse reaction of VGB that limits its clinical application. Increasing evidence has demonstrated that, apart from acting on the GABA ergic system, VGB exerts an antiepileptic effect via regulating the metabolic changes of tissue endogenous substances including β-alanine, aspartic acid, ornithine, as well as the function of mechanistic target of rapamycin (mTOR) signalling pathway. In this article, we mainly review the progress of the studies focusing on mechanism, metabolism, and distribution of VGB, which will be helpful to understand the pharmacodynamics and toxic and side effects of VGB in depth.
To provide reference for improving the management of innovative drug clinical trial in China.
From the perspective of the project whole life cycle, this paper analyzes the complex project system of innovative drug clinical trials, discusses the measures and regulatory experience in promoting the development of innovative drug clinical trials in the United States, hoping the suggestions were useful for China.
The process of innovative drug clinical trial projects is complex and the interests of different subjects are different, therefore certain regulatory difficulties exist. Through timely promulgation of various modern regulatory program and clinical trial guidance documents, the United States has promoted the rigor and efficiency of innovative drug clinical trials in the whole life cycle process of protocol design, review and approval, study start-up, ethical review, and data sharing. It is suggested that China should optimize the management path of innovative drug clinical trials from the following aspects, and explore the "master protocol" trial design model to provide further guarantee for clinical trials of new therapies: initiating operation procedures based on optimized trial, applying parallel mechanism of independent review and specialized ethical review, and using diversified data sharing models, in order to ensure efficient clinical trials. The review information disclosure and stakeholder communication mechanism should be constantly improved to strengthen the guidance of innovative drug clinical trial project.
To investigate the effect of agarwood line incense (ALI) burning on anxiety and depression and its mechanism.
Chronic unforeseeable mild stress (CUMS) was applied to induce depression-like model and M-chloropheniperazine (MCPP) was applied to induce anxiety model. By using open field test (OFT), light-dark transtition test (LDT), tail suspension test (TST) and forced swim test (FST), changes of activity after inhaling the incense were measured to evaluate its effects of anti-anxiety and anti-depression. To investigate the mechanism, monoamine neurotransmitters in brain, such as 5-HT, Glu, and GABAA, were observed by ELISA. The protein expression levels of GRN2B, GRM5, GluR1, VGluT1 were evaluated by Western Blot.
Compared with the anxiety model group, the total distance and average velocity significantly reduced (P<0.05), the rest time increased (P<0.05), and the distance and average velocity in the black box reduced (P<0.05) in ALI inhalation group. Compared with the depression model group, the total distance and average velocity significantly increased (P<0.05), the rest time decreased (P<0.05), and the immobile time of TST and FST decreased (P<0.05) in the ALI group. The ALI inhalation increased the levels of 5-HT and GABA (P<0.05), decreased the level of Glu (P<0.05) in the brain tissues of the anxiety model group. ALI decreased the level of GABA (P<0.05), and increased the levels of 5-HT and Glu (P<0.05). ALI increased the protein expression levels of GRN2B, GRM5, GluR1, and VGluT1 in hypothalamus of the rats in anxiety model group. ALI decreased the protein expression of GRM5 and increased the protein expressions of GRN2B, GluR1, and VGluT1 in hypothalamus of the rats in depression model group.
ALI has a significant anxiolytic and anti-depression effects, and the mechanism may be related to the regulation of the levels of 5-HT, Glu, GABAA, and the protein expression of GRN2B, GluR1, and VGluT1 in hypothalamus.
To determine the index weight coefficient, optimize the ultrasonic extraction process of flavonoids in Scutellaria baicalensis Georgi and analyze its anti-inflammatory activity in vitro.
On the basis of single factor test, ethanol concentration (A), ultrasonic time (B), ultrasonic temperature (C) and material-to-liquid ratio (D) were selected as the investigation factors. Taking baicalin, wogonin, baicalein and wogonin as the inspection indicators, the AHP-CRITIC mixed weighting method was used to determine the weight coefficients of each index, multivariate binomial was fitted combined with the response surface method, a three-dimensional graph was drawn, and the best extraction process was chosen. At the same time, the MTT method and Griess method were used to evaluate the in vitro anti-inflammatory activity of the ultrasonic extraction of Scutellaria baicalensis Georgi.
The optimal extraction conditions for flavonoids in Scutellaria baicalensis Georgi were as follows: ethanol concentration of 62.73%, ultrasonic time of 32.23 min, ultrasonic temperature of 51.15 ℃, and material-to-liquid ratio of 1∶16.12. The average AHP-CRITIC comprehensive score of three batches of verification samples was 85.28, and the RSD with the theoretical prediction value was 0.50%. The results of MTT method showed that when the concentration of Scutellaria baicalensis Georgi extraction was greater than 400 μg·mL-1, the cell viability decreased significantly (P<0.05, P<0.01). When the concentration of Scutellaria baicalensis Georgi extraction was 50~350 μg·mL-1, the release of NO in RAW264.7 inflammatory cells was significantly inhibited (P<0.05, P<0.01).
The method is stable and reliable and can be used for the extraction of flavonoids from Scutellaria baicalensis Georgi, and the ultrasonic extract has strong anti-inflammatory activity in vitro.
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