The US FDA has recently issued the Platform Technology Designation Program for Drug Development Guidance for Industry, providing a new avenue for improving the efficiency of drug development, manufacturing, and review processes. The guidance elaborates on key elements such as the application conditions for platform technology designation, potential benefits, data utilization, discussions in milestone meetings, application content, and the review schedule. This guidance offers important insights for the regulation of cell and gene therapy (CGT) in China. Chinese regulatory agencies can draw on American experience to establish a similar framework for the designation of platform technology, strengthen communication between regulatory agencies and enterprises, and promote international exchange of experiences, in order to advance innovation and standardized development in the CGT industry, and enhance patient access to advanced medical products.

Based on the construction of the three-dimensional efficacy evaluation index system of “disease-syndrome-person”, following the principle of combining subjective and objective indicators, doctor and patient reported outcomes, disease of Western medicine and syndrome of traditional Chinese medicine (TCM), and qualitative and quantitative research methods, this study aimed to achieve the goal of multi-index, multi-dimensional and comprehensive evaluation of clinical efficacy of TCM. The efficacy of TCM syndrome is conspicuously characteristic and the best example of efficacy evaluation indicators of TCM. However, the uncertainty of scientific connotation, evaluation ideas and methods, and key technologies of the efficacy of TCM syndrome results in confusion and heterogeneity of evaluation indicators, thus limiting the construction of efficacy evaluation indicator system of TCM. This study elucidated the multi-level, multi-dimensional and multi-perspective scientific connotation, clarified the evaluative dimension of patient and doctor-reported outcome indicators and objective biological indicators, advised using syndrome efficacy evaluation scales to evaluate the efficacy of Chinese medicine syndrome, and established the structure of the evaluation indicator system of TCM, to achieve  scientific, objective, quantitative and standard evaluation of the efficacy of TCM syndrome and  evaluating the efficacy of TCM with a multi-index and multi-dimension system.

The new Patent Law of the People's Republic of China establishes for the first time the provisions of patent term extension for an invention patent relating to a drug. The new Detailed Rules for the Implementation of the Patent Law of the People's Republic of China and Patent Examination Guidelines revised in 2023 provided detailed provisions and explanations. This paper analyzed the applicable objects, request conditions, calculation method of patent term extension, subject and process of request stipulated in the new Detailed Rules and Guidelines and compared them with the relevant provisions in the United States and Japan. The current situation of drugs in the application stage and the situation of recently approved drugs was also analyzed. Based on the provisions of the new Detailed Rules and Guidelines, the length of time for which the recently approved drugs can be extended for the patent term was calculated, and suggestions for enterprises to request for extension for the patent term of drugs were put forward.

Objective: To sort out the key issues in the clinical data submitted by medical institutions using traditional techniques to prepare traditional Chinese medicine (TCM) preparations and provide solutions to the problems to further improve the quality of research and development of TCM preparations in medical institutions. Methods: Through a combination of literature analysis and retrospective analysis, the issues in the clinical data of TCM preparations prepared by medical institutions using traditional techniques were explored. Results: When medical institutions use traditional techniques to prepare TCM preparations for filing, they should focus on key issues such as the application of fixed prescriptions, clinical supporting evidence such as preparation functions and indications, usage and dosage, adverse reactions, and the reliability of the provided clinical data. Special attention should be paid to the clinical positioning and clinical value of TCM preparations. Conclusion: Medical institutions should pay attention to the integrity, standardization and scientificity of the clinical data in the filing of TCM preparations prepared by traditional techniques, highlight the clinical value of TCM preparations, and promote the inheritance, innovation and development of TCM.

The defense of uncertainty protects the interests of the party who performs first in a dual contract where there is an agreement on the order of performance. However, in the case of generic drug development contracts, the defense of uncertainty based on the risk of patent infringement faces a difficult determination. Theoretically, the court's determination of the defense of uncertainty mainly examines whether the party claiming the right has fulfilled the burden of proof and the duty of notification. In practice, the court mainly makes separate judgments on form and substance and identifies them according to the characteristics of the industry involved. The obstacles to establishing the defense of uncertainty include the Bolar exception exemption, failure to provide notification, and the difficulty of proving patent infringement. The successful assertion of the defense of uncertainty requires specificity and comprehensiveness in the formation of the contract and honesty and integrity in the performance of the contract. Considering the special characteristics of generic drug development, adequate prior patent infringement risk assessment, control of raw and auxiliary materials and reference preparations, as well as the early resolution of pharmaceutical patent disputes are conducive to eliminating the limitations of the defense of uncertainty.

Ribociclib is a selective, orally bioavailable small molecule inhibitor of cyclin-dependent kinases 4/6 （CDK4/6）, which was approved by the National Medical Products Administration on January 19, 2023, and officially launched in China on February 18, 2023. It is indicated for the treatment of locally advanced or metastatic breast cancer that is hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-). Ribociclib is the first and currently the only CDK4/6 inhibitor approved for initial treatment of premenopausal and perimenopausal patients with breast cancer in China. This article reviews the mechanism of action, pharmacokinetics, pharmacodynamics, clinical studies, and safety evaluation of this drug, with the aim of providing references for new drug development and clinical application of ribociclib.

In the process of drug research and development, registration, production, supervision, inspection and verification, guidance plays a dual role of regulatory basis and technical requirements. Improving the full lifecycle management of guidance helps to form a scientific, open, transparent, and socially participatory standard system. The guidance of the FDA can be traced back to 1902. FDA introduced the Good Guidance Practice (GGP) in 1997, which clarifies the nature and effectiveness of guidance principles at the regulatory level and standardizes the process of formulation and revision. FDA released reports in 2011 and 2023, summarizing the phased implementation progress of GGP by FDA and various centers/offices, and plans to further optimize and form Best Practices for Guidance. This study combines the formation and update trajectory of FDA-issued guidance to sort out the current situation of FDA's initiation, drafting, review, release, and update of guidance, providing reference ideas for the full lifecycle management of guidance in China.

Objective: To optimize the induction and culture method of umbilical cord blood CD34⁺ hematopoietic stem cell derived dendritic cell (DC) in vitro, prepare DC vaccine loaded with tumor cell lysate, and explore the anti-breast cancer activity of DC vaccine. Methods: CD34⁺ hematopoietic stem cells were obtained after umbilical blood mononuclear cells were sorted by immunomagnetic beads. The purity of CD34⁺ hematopoietic stem cells was determined by flow cytometry, and DC was obtained by amplification culture and induced differentiation culture. The influence of different factors added in different combinations and different times on the phenotype of the obtained DC was compared. Flow cytometry was used to detect the antiphagocytotic activity of DC on FITC-OVA, CCK-8 method was used to detect the ability of DC vaccine to stimulate the proliferation of heterologous umbilical blood mononuclear cells, and LDH method was used to detect the in vitro killing activity of T cells activated by DC vaccine loaded with tumor cell lysate antigen on breast cancer cells. Results: During amplification and culture, IMDM medium+GM-CSF (100 ng·mL^－1)+SCF (50 ng·mL^－1)+Flt-3L (100 ng·mL^－1)+TPO (100 ng·mL^－1)+10% FBS+1% P/S condition culture group and IMDM medium+GM-CSF (100 ng·mL^－1)+SCF (50 ng·mL^－1)+10% FBS+1% P/S, there was no significant difference in the phenotype of harvested DCs, but the former group could harvest more DCs. In the induction differentiation stage, the expression of CD80 and CD83 of the harvested DC was higher when TNF-α was added 48 hours after the addition of GM-CSF and IL-4 than at other time. Flow cytometry showed that immature DC had strong antigen-phagocytosis activity. DC vaccine showed a strong ability to stimulate the proliferation of heterologous cord blood mononuclear cells. T cells activated by DC vaccine loaded with tumor cell lysate antigen showed significant killing activity against different breast cancer cell lines in vitro. Conclusion: Cord blood hematopoietic stem cells can differentiate into a considerable number of functional DC, and DC vaccine loaded with tumor cell lysate antigen can activate T cells and have significant killing activity against breast cancer cell line.

Traditional new drug research and development (R&D) has problems such as long period, high cost, and high failure rate. In order to overcome the above problems, organ-on-a-chip technology comes into being, which plays a huge role in the R&D of new drugs as an emerging frontier technology in recent years. This article focuses on the application of organ-on-a-chip in the R&D of new drugs and its potential applications in the field of nuclear drug R&D, and discusses the opportunities and challenges faced by organ-on-chip, so as to provide references for new drug R&D practitioners.

Error correction is crucial for next-generation sequencing applications, as highly accurate sequencing readings can yield higher quality results. Error-corrected double sequencing (ecNGS) based on consensus sequencing can directly quantify low-frequency mutations and provides enormous potential for chemical mutagenicity assessment, rapidly becoming a valuable, highly sensitive, and accurate method. Recent studies on mutagenicity and carcinogenicity have used ecNGS to quantify chemically-induced mutations and mutation profiles associated with cancer risk, which plays an important role in genetic toxicity testing and carcinogenicity assessment. The three common methods of ecNGS have different application prospects in genetic toxicity and carcinogenicity detection. In addition, ecNGS has also played an important role in human-related regulation. Finally, prospects for the application of ecNGS were proposed, which could further develop ecNGS technology and include its endpoints in non-clinical safety studies to supplement or provide references for replacing current testing methods in some cases.

Objective: To evaluate the efficacy and safety of multi-trace element injection I [MTEI-(I)] for parenteral nutrition in preterm low birth weight (LBW) infants. Methods: From March 2020 to August 2020, infants with GA＜37 weeks and BW＜2 500 g admitted to NICU within 24 hours after birth were included. PN with MTEI-(I) at 1 mL·kg^－1·d ^-1 was administered to the infants. The serum trace element levels were detected by ICP-MS pre- and post-supplementation. The body weight was daily measured. The body length, head circumference, pre-albumin (pre-ALB), albumin (ALB), C-reactive protein (CRP), procalcitonin (PCT), routine blood tests, liver and kidney functions and adverse drug reactions (ADR) were monitored. Results: A total of 43 preterm infants were enrolled, including 22 male infants (51.2%) and 21 female infants (48.8%) with GA of (31.4±2.4) weeks and BW of 1430(1 200, 1 830) g. Administration of MTEI-(I) in parenteral nutrition was initiated 2(1, 2) days after birth, and continued for 11(9, 17) days. Serum Cu and Se levels were significantly higher than those pre-parenteral nutrition (P＜0.05), whereas serum Mn levels were significantly lower than those before (P＜0.05). No significant differences were observed in serum Zn levels (P＞0.05). A significant positive correlation between serum Zn levels after supplementation and weight growth velocity in hospitalized preterm LBW infants was found (P＜0.05). Serum Se levels were positively correlated with weight and weight-for-age z scores at discharge (P＜0.05). After MTEI-(I) was administered, PCT, aspartate transaminase (AST), gamma glutamyltransferase (GGT), total bilirubin (TB), and blood urea nitrogen (BUN) were significantly lower (P＜0.05), while pre-ALB, alkaline phosphatase (ALP), direct bilirubin (DB), and creatinine (Cr) were significantly higher (P＜0.05). No significant ADR were observed except for one infant with parenteral nutrition-associated cholestasis (PNAC). Conclusion: Parenteral supplementation of MTEI-(I) at 1 mL·kg^－1·d ^-1 is safe for preterm LBW infants and might increase serum Cu levels, maintain the levels of serum Zn and Se, and improve serum Mn levels.

Objective: To investigate the prevention and treatment effect of Xiang Huo Spray (XHS) on upper respiratory tract infection in mice. Methods: The anticough and expectorant effects of XHS and its effect for improvement of acute rhinitis were evaluated by using concentrated ammonia water cough model, phenol red excretion model and acute rhinitis model induced by xylene in mice. The release of pro-inflammatory mediators from mouse macrophages induced by LPS, disk diffusion and double dilution method were used to detect the anti-inflammatory and antibacterial effect of XHS on major respiratory pathogens in vitro. Results: XHS can significantly reduce the frequency of cough and increase the amount of phenol red in the trachea of mice, improve the pathological changes of acute rhinitis in mice, and reduce inflammation and bleeding. XHS can significantly inhibit the release of pro-inflammatory mediators and has obvious antibacterial activity against major respiratory pathogens in vitro, showing good anti-inflammatory and antibacterial effects in vitro. Conclusion: XHS has the pharmacological effects of relieving cough and resolving phlegm, anti-inflammation and antibacterial. It can significantly improve the pathological changes of acute rhinitis in mice, reduce inflammation and bleeding, and has a certain prevention and treatment effect on upper respiratory tract infection.

Objective: To study the preparation and quality evaluation of lansoprazole enteric orally disintegrating tablets. Methods: The formulation was optimized by orthogonal design, using the comprehensive score of friability, disintegration time, and dissolution in acid at 60 min as index. Results: The best formula was composed of microcrystalline cellulose 20%, magnesium stearate 2%, crospovidone 7%, and lansoprazole enteric pellets 15%. The friability, disintegration time, assay and content uniformity of the three batches conformed to the requirements. Samples were put at 40 ℃ condition for 6 months, and  there was no significant change in friability, disintegration time, assay, impurity, and dissolution. Conclusion: The lansoprazole enteric orally disintegrating tablets prepared by the optimized method has a flat appearance and stable quality.

Objective: To establish an HPLC method for simultaneous determination of 10 components (gallic acid, epicatechin, ellagic acid, myricetin, cinnamic acid, eugenol, hesperidin, alpha-asarol and chrysophanol) in a Mongolian medicine, Menggen Vos-18 pills, and verify the feasibility of applying this method in its quality analysis. Methods: The chromatography was performed on Agilent Eclipse Plus C₁₈ column (250 mm×4.6 mm，5 μm) with mobile phase consisting of acetonitrile (A)-0.2% phosphoric acid solution (B) and gradient elution (0~60 min, 5%A→25%A, wavelength 210 nm; 60~80 min, 25%A→36%A, wavelength 280 nm; 80~145 min, 36%A→75%A, wavelength 254 nm), and the flow rate was 1.0 mL·min^－1. The column temperature was 40 ℃. Relative correction factors (f_s/i) were established with ellagic acid as the internal reference, the mass fractions of each component were calculated by relative correction factor, and the results were determined by external standard method. The accuracy of the application of quantitative analysis of multi-components by single marker (QAMS) method in Menggen Vos-18 pills was evaluated. Results: The f_s/i reproducibility of gallic acid, epicatechin, myricetin, cinnamic acid, eugenol, hesperidin, manpinone, alpha-asarol and chrysophenol in Menggen Vos-18 pills was good. They were 0.242 2, 0.231 5, 0.319 9, 0.256 5, 1.969 9, 1.208 9, 1.260 2, 0.560 5 and 1.213 2, respectively. The results obtained by QAMS method and external standard method were close to each other. Conclusion: The method is simple, stable and reproducible, and can be used for the quality control of Mengen Vos-18 pills.

icariin; resveratrol；anti-aging；decayacceleratingfactor-16；superoxide dismutase-3

Objective: To mine and analyze the adverse events of vemurafenib after marketing to provide a reference for clinical rational medication. Methods: Adverse drug event (ADE) reports of vemurafenib since its marketing were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Combined reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) methods were used to explore and screen the ADE signals of vemurafenib, and the obtained ADE signals were compared with drug instructions. Potentially suspicious newly discovered adverse drug reactions were mined. Results: A total of 314 ADE signals of vemurafenib were mined, involving 25 system organ classes (SOCs), mainly including skin and subcutaneous tissue diseases, systemic diseases and various reactions at the drug administration site, musculoskeletal and connective tissue diseases, etc. Thirty-two adverse reactions that were not recorded in the instructions were obtained, mainly including elevated blood lactate dehydrogenase, acneiform dermatitis, sarcoid disease, and dysplastic nevus. Conclusion: The adverse effects of vemurafenib in the real world are consistent with the drug label. However, there are some potentially suspicious new adverse effects. During the treatment with vemurafenib, clinicians should pay enough attention to these adverse reactions.

Objective: Based on the literatures on pharmacoeconomic evaluation of oral and intravenous dosage forms of drugs with the same chemical name or category for the treatment of the same disease, this article analyzes and discusses how to quantify the differences caused by different dosage forms in pharmacoeconomic evaluation. Methods: The relevant literature on pharmacoeconomic evaluation of oral and intravenous dosage forms was collected from online database CNKI, Wanfang Data, Vip, PubMed, Wiley online library, etc., and the literature meeting the standard of inclusion and exclusion criteria was sorted out and summarized. Results: A total of 18 literatures were included in the study. The result suggested that compared with the intravenous dosage form, the oral dosage form not only saves the cost of consumables such as intravenous syringes and infusion tubes, reduce nursing time and save human resources, but also saves the cost of medical transportation and loss of work hour under the scenario of home treatment. In addition, some studies also considered that oral dosage forms can improve the patients' health effectiveness and medication compliance, thus their health benefits were included in the calculation of economic evaluation. Conclusion: Differences in dosage forms may lead to differences in cost, efficacy and incidence of complications, which should be reasonably quantified and reflected in pharmacoeconomic evaluation. In addition, in the case of different treatment scenarios (such as inpatient intravenous injection and home oral administration), the treatment experience of patients with different dosage forms may be remarkably different, which should be included in the calculation of drug evaluation studies.

Objective: To provide reference for clinical safe drug use by signal mining and analysis of adverse drug events （ADEs） of intravenous and oral iron preparations. Methods: Based on the reports in Chengdu database of the National Adverse Drug Reaction Monitoring System from the first quarter of 2011 to the fourth quarter of 2023, the adverse drug reaction signals produced by iron sucrose injection, iron dextran injection, polysaccharide iron complex, and ferrous succinate were mined. The reporting odds ratio (ROR) method was used to mine and analyze the related data. Results: Thirty-six ADE signals were found by ROR signal detection method, which had high correlation strength between iron sucrose injection and iron dextran injection, mainly involving injection site reaction, systemic administration reaction, disease of respiratory system and allergic reaction. However, polysaccharide iron complex and ferrous succinate-related ADEs were mainly associated with gastrointestinal damage. Conclusion: The organs/systems involved with the ADE signals of four kinds of iron preparations are different, and the analysis of the data can provide help for clinical drug selection.