Objective: To clarify the remodeling effect, technical paths, and key challenges of the integration of artificial intelligence (AI) and genomic sequencing on the clinical diagnosis paradigm, and to provide a systematic reference for researchers, clinicians, and regulatory authorities in the medical and health field for the coordinated development of technology and regulation, thereby facilitating the standardized application and clinical translation of the integration. Methods: This study systematically reviewed the evolutionary trajectory of genomic sequencing technology and the current application status of AI in the medical field. It conducted an in-depth analysis of two types of technical pathways for their integration, namely, “direct integration”, focusing on the analysis of genomic data and the exploration of molecular mechanisms, and the “extended integration” integrating multimodal data such as medical images and electronic medical records to achieve clinical phenotype association. Additionally, it comprehensively assessed the key challenges in the integration process from the dimensions of technology, data, ethics and law, and clinical translation. Results and Conclusion: AI and genomic sequencing form an efficient synergy through the collaborative architecture of “data layer-algorithm layer-application layer-decision-making layer”, which can break through the limitations of traditional clinical diagnosis. Specifically, it enables early screening and precise subtyping of cancer, shortens the diagnostic cycle of genetic diseases, and accelerates pathogen identification and drug resistance prediction of infectious diseases. As a core driving force for the development of clinical diagnosis toward precision and intelligence, it provides critical technical support for the practice of precision medicine. However, their integration faces prominent challenges, including the mismatch between algorithm complexity and computing power, the “black-box” nature of AI models, the data platform heterogeneity and “data silos”, the ambiguous boundaries of genetic privacy, and the insufficient adaptability to clinical real scenarios. To solve these multi-dimensional bottlenecks and ultimately promote the standardized application and efficient clinical translation of their integration, future efforts should focus on: technological integration and innovation by advancing explainable AI (XAI) and multimodal data fusion to enhance model transparency and multi-dimensional data association; interdisciplinary collaboration by establishing research teams with experts from multiple fields such as medicine, computer science, biology, and ethics, to provide comprehensive support for technological research and development, clinical needs, and ethical oversight; and policy and regulatory improvement by clarifying the boundaries for the collection, storage, and use of genetic information and establishing a multi-subject collaborative responsibility identification mechanism for AI diagnostic decisions.

Objective: To explore the potential application of DNA methylation detection based on next-generation sequencing (NGS) for early screening of solid tumors, and to analyze the standardization issues in assay development, quality control, and performance evaluation, thereby providing references for future clinical translation. Methods: Key steps of methylation sequencing in tumor early screening were systematically reviewed, including cancer type selection and biomarker discovery, methylation conversion approaches (chemical and enzymatic methods), library preparation strategies (single-strand and double-strand), sequencing platform differences (Illumina vs. BGI DNBSEQ), and calculation approaches for methylation signals. The application and performance of various modeling methods (logistic regression, decision tree, random forest, gradient boosting tree, etc.) were compared, and the current practices and challenges in quality control and clinical validation were summarized, focusing on reference material preparation, plasma matrix evaluation, and performance metrics. Results: In library preparation, chemical conversion offers lower cost but causes severe DNA degradation, whereas enzymatic conversion is milder but technically more complex. Single-strand libraries provide higher fidelity, while double-strand libraries are more established and scalable. Different sequencing platforms exhibit systematic differences in GC-region coverage and methylation signal measurement. The computational strategies and algorithms used for biomarker modeling significantly affect model performance, with ensemble learning methods (random forest, gradient boosting tree, etc.) generally achieving higher sensitivity and specificity than traditional models (logistic regression, decision tree, etc.). Consequently, ensemble models are often applied in large-scale clinical cohorts and product development, while traditional models remain valuable for mechanism exploration and biomarker selection due to their interpretability. Reference materials prepared from cell line DNA provide consistency and scalability but require fragmentation and gradient design to mimic plasma cfDNA. Plasma matrix interference from residual human DNA may bias methylation signals and represents a critical issue for quality control. Moreover, the limited accuracy of early cancer detection reduces the reliability of positive results, potentially leading to unnecessary medical interventions and underscoring the necessity of clinical validation. Conclusion: NGS-based methylation detection offers a promising approach for early cancer screening, with advantages in multi-target detection and tissue-of-origin analysis. However, its clinical implementation relies on the establishment of standardized workflows, robust quality control systems, and comprehensive performance evaluation frameworks. Future efforts should focus on developing reference standards, optimizing quality control checkpoints, and advancing clinical validation studies. These steps are crucial to assessing the feasibility and standardization of multi-cancer early detection in clinical practice.

Objective: To study the standardized system for next-generation sequencing databases, explore the role of standardized gene databases in ensuring the scientificity, accuracy, and traceability of regulation, and promote the construction of an interactive “database-standard-application” system connecting the industry, clinical practice, and regulation. Methods: The roles, functions, and application scenarios of databases centered on supporting clinical research and/or product evaluation were reviewed. The composition, product quality evaluation functions, and regulatory support roles of the five databases developed by the National Institutes for Food and Drug Control (NIFDC) were analyzed. Results and Conclusion: The five databases developed by the NIFDC include the next generation sequencing performance evaluation database, the mutation interpretation evaluation database for breast cancer susceptibility genes BRCA1/2, the standardized evaluation database for tumor mutational burden (TMB), the standardized evaluation database for homologous recombination deficiency (HRD), and the pathogenic microbial genome reference database. Characterized by clear application scenarios, controllable quality, and direct practicality, these databases provide technical requirements and operational specifications for the quality evaluation of domestic marketed sequencing products and innovative medical devices. Through the systematic management of genetic data regarding specifications, standards, and safety, this database system establishes a solid and reliable data foundation for regulatory decision-making and advances the standardized development of the industry.

Objective: To systematically elaborate on the considerations and requirements for using Sanger sequencing technology as a comparative method in clinical trials, providing reference for the design of clinical trials. Methods: This study summarizes and analyzes the application scenarios and roles of Sanger sequencing technology in the clinical trials of in vitro diagnostic reagents. Based on the characteristics of this technology, it conducts an in-depth analysis of considerations during the technical review of related product clinical trials, covering aspects such as relevant regulatory requirements, establishment of the Sanger sequencing method, performance evaluation of the sequencing method, quality control, and limitations of selecting this method as a comparative approach. Results and Conclusion: Sanger sequencing technology plays a very important role as a clinical reference method in the clinical trials of in vitro diagnostic reagents. For molecular diagnostic products, whether this technology can be selected as a comparative method during clinical trials should be considered based on both the characteristics of the product itself and the performance of Sanger sequencing technology. When choosing Sanger sequencing technology as a comparative method, sufficient research should be conducted in areas such as method establishment, performance evaluation, and quality control, so that the clinical trials can more scientifically and reasonably evaluate the clinical performance of the product and facilitate timely regulatory approval.

Objective: To systematically elaborate on the approval overview and key considerations for the clinical evaluation of companion diagnostic reagents based on next generation sequencing (NGS), thus providing a reference for the clinical evaluation of such products. Methods: This article systematically reviews the importance and advantages of NGS technology in the field of companion diagnostics. It details and compares the product profiles, regulatory pathways, and characteristics of NGS-based companion diagnostic reagents for anti-tumor drugs approved by the U.S. Food and Drug Administration and China’s National Medical Products Administration. Furthermore, this article explores the core challenges and technical considerations in the clinical evaluation of such products during the registration technical review, aiming to provide references for their development, registration, and clinical evaluation. Results and Conclusion: Applicants should design scientifically sound clinical trial protocols tailored to the high-throughput, multi-gene parallel detection features of NGS technology in their clinical evaluations to facilitate the market approval of these products.

Objective: Traditional Chinese medicine (TCM) preparations used in healthcare institutions serve as important vehicles for the inheritance of TCM and a major source for the development of new TCM drugs. However, owing to the chemical diversity and mechanism complexity of TCM, the research and translation of TCM preparations face substantial challenges in component selection, dose determination, optimization of manufacturing processes, verification of safety and clinical efficacy, formulation of relevant regulations, and market acceptance. This expert consensus on the application of network pharmacology based on the “network target” theory aims to establish a universal technical framework and standardized pathways for enhancing the scientific rigor and translational efficiency of TCM preparations. Methods: Current policies and regulations, such as the Special Provisions for the Registration Administration of Traditional Chinese Medicines, as well as international standards including the Network Pharmacology Evaluation MethodGuidance, were systematically reviewed. Through multicenter research practices and expert consultations, an expert consensus was formulated to define the role of network pharmacology across the entire life cycle of TCM preparations. Results and Conclusion: This expert consensus delineates standardized translational stages and key technical requirements for applying network pharmacology to TCM preparations. Through representative case studies, it illustrates the practical value of network pharmacology in identifying key potential bioactive components, preliminarily evaluating potential toxicity, and optimizing formula composition and dosage. Network pharmacology based on the “network target” theory represents a novel methodology and tool for the scientific interpretation of empirical human-use experience of TCM preparations, enabling effective integration of evidence for clinical efficacy and pharmacological plausibility.

Objective: To investigate the core causes of data packet loss triggered by signal interference when implantable telemetry technology is applied to non-clinical safety pharmacology research of drugs, and further propose targeted optimization strategies to improve the data quality and application reliability of this technology in safety evaluation. Methods: Based on the working principle of radio frequency (RF) wireless transmission, the core interfering factors leading to data packet loss under complex experimental conditions, such as co-frequency signal interference, external noise intrusion, were systematically dissected, then a suite of comprehensive strategies encompassing operating frequency band switching, spatial layout optimization, and electromagnetic shielding enhancement was adopted for in-depth empirical investigation and validation to tackle it. Results: Experimental results demonstrated that in a 5G signal interference environment, the average data packet loss rate of original F4 frequency band telemetry system was approximately 8%. After systematic optimization and switching to the F3 frequency band (915-925 MHz), the data packet loss rate was drastically reduced, which substantially enhanced the integrity and reliability of experimental data captured at critical time points pre- and post-drug administration. Conclusion: By proposing targeted technical and managerial optimization strategies addressing interference sources, the data packet loss rate of implantable telemetry systems can be effectively reduced. This not only ensured the reliability and integrity of data acquired by implantable telemetry technology but also provided robust and stable technical support for non-clinical safety evaluation of pharmaceuticals.

Objective: To introduce the inspection points and judgment principles for clinical trials of in vitro diagnostic reagents issued by the National Medical Products Administration (NMPA) in 2025, and analyze common issues identified during on-site inspections, aiming to provide references for the conduct of clinical trials. Methods: By presenting the major revisions in the newly issued inspection points and judgment principles, and by analyzing common findings observed during on-site inspections of in vitro diagnostic reagent clinical trials organized by the Yangtze River Delta Center for Medical Device Evaluation and Inspection of NMPA, this paper proposed recommendations for improving the quality of in vitro diagnostic reagent clinical trials. Results and Conclusion: The newly released inspection points and judgment principles for in vitro diagnostic reagents aligned with current clinical trial regulatory requirements, strengthened oversight of the trial implementation process, and demonstrated improved scientific rigor and standardization. Common deficiencies in clinical trials of in vitro diagnostic reagents mainly involve the trial implementation process and the management of investigational in vitro diagnostic reagents, associated reagents, and instruments. This paper recommends that sponsors and clinical sites reinforce adherence to requirements regarding screening, enrollment, testing and documentation during trial implementation. Furthermore, regulatory authorities should refine inspection specifications and enhance pre-inspection guidance, thereby collectively improving the quality of clinical trials.

Objective: To enhance the understanding and cognition of capability assessment among drug inspection and testing institutions in China, and lay a foundation for the comprehensive implementation of capability assessment and the high-quality development of the drug inspection and testing industry. Methods: A comparative study was conducted on the similarities and differences among the capability assessment of drug inspection and testing institutions, ISO/IEC 17025:2017 and the “Review Criteria for Qualification Accreditation of Inspection and Testing Institutions”. Results: The capability assessment of drug inspection and testing institutions, in terms of basic indicators and technical indicators, can partially correspond to the resource and management requirements of ISO/IEC 17025:2017 and the “Review Criteria for Qualification Accreditation of Inspection and Testing Institutions”. However, its core lies in the inclusion of service and innovation indicators not covered by the latter two, and it focuses on the systematic evaluation of the institutions’ core function performance and their capabilities to respond to future challenges. There are essential differences between the capability assessment and the latter two in terms of purpose, nature, scope and application. Conclusion: Different from certification and accreditation, the capability assessment for drug inspection and testing institutions is a self-identification of the institutional capacity building, a feasible tool for evaluating their own strengths and weaknesses, and an important means for institutions to continuously improve and enhance their capacity.

Objective: To improve the development of social organization standards of traditional Chinese medicine (TCM) and propose recommendations to address the existing problems. Methods: The current status of social organization standards of TCM was reviewed, the quantity and classification of these standards were analyzed to identify the existing problems. Results and Conclusion: As of April 30, 2025, a total of 176 social organizations at various levels registered in China have been involved in the development of TCM group standards, with 1338 social organization standards of TCM having been formulated. Among these, 811 were formulated by national-level social organizations, 382 by provincial-level organizations, 70 by city-level organizations, and 75 by county- or district-level organizations. In terms of standard content, TCM product quality standards, cultivation and planting specifications, and seed and seedling standards accounted for nearly 70% of all TCM group standards. There were some issues in the work related to TCM social organization standards, such as the imbalance between quantity and quality development, insufficient sustainable development capabilities, and inadequate overall coordination. Efforts should be made to enhance the integration of TCM social organization standards into the TCM standard system. The management regulations and working mechanisms should be improved and the self-construction of social organization standardization capabilities should be strengthened.

Objective: To carry out a quantitative traceability study on cystatin C, and to develop cystatin Cfrozen human serum national standard, which can be used for evaluating the accuracy of cystatin C test kits,and improving the ability of human serum cystatin C detection. Methods: Human serum samples were used asraw materials for aseptic sub-packaging and preparation of cystatin C frozen human serum national standard.The candidate of cystatin C frozen human serum national standard was assigned and calibrated by the method of multi-laboratory joint assignment, which was traceable to the international standard ERM-DA471/IFCC, and theaccuracy of the traceability chain has been verifi ed. The homogeneity and stability of the national standard wasverifi ed by the method of immune turbidimetry. Results: The cystatin C frozen human serum national standardwas established, which contains two concentration levels: level 1 (0.94 ± 0.03) mg·L^-1 (k=2), Level 2 (3.52 ± 0.09)mg·L^-1 (k=2); cystatin C frozen human serum national standard has good homogeneity and stability. The resultsof the 30-day short-term stability study showed that cystatin C frozen human serum national standard (level 1 andlevel 2) were stable for 5 days at room temperature; at 2-8 ℃, level 1 can be stable for 10 days and level 2 canbe stable for 20 days. At -20 ℃, both level 1 and level 2 can be stable for at least 30 days. The accuracy of thetraceability was verifi ed by using the serum reference panel and clinical serum samples, study results show that thenational standard and international standard ERM-DA471/IFCC have good traceability. Conclusion: The CystatinC frozen human serum national standard (360046-202001) has been approved and provided to the society withthe quantitative traceability study, which can be used for the accuracy evaluation of the cystatin C detection kit inhuman serum and the accuracy evaluation of clinical laboratory detection system values.

Objective: To explore potential problems in current reference materials development by selectingone representative with important clinical signifi cance for evaluation, and to discuss the optimization of producedpath according to the results to better improve the standardization of inspection reference system, based on thestatus of biochemical and immunological standard reference materials in the clinical reference system. Methods:According to the standards of EP14-A3 of the Clinical and Laboratory Standards Institute and WS/T 356-2011 of the National Center for Clinical Laboratories, the evaluation scheme was set up. 4 creatinine in frozen humanserum reference materials produced by reference methods from two diff erent domestic organizations and 21 freshhuman serum samples, were tested by reference methods of isotope dilution mass spectrometry and conventionalmethods of sarcosine oxidase according to the scheme. After processing the test results, the accuracy, matrixeff ects and commutability of the reference materials were studied. Results: The result of 4 reference materials and21 fresh human serum samples displayed diff erence in accuracy and matrix eff ect including reference methods andconventional methods. Three reference materials cannot ensure that the results within the range of target value ±uncertainty from reference methods, the deviation of GBW09170 and GBW09171 increased in the conventionalmethods, GBW09171 also showed matrix eff ects. Conclusion: Clinical applicability should be fully consideredin the development process of biochemical and immunological standard reference materials. When referencemethods are used to produce biochemical and immunological reference materials, such as creatinine in thisevaluation, attention should be paid to the diff erence of diff erent reference methods, and joint assignments shouldbe considered. At the same time, the commutability among diff erent methods should be fully considered to ensurethe accurate transfer of quantitative values as for optimization of produced path, supporting precision medicine.

Objective: To discuss the key requirements of quality control technology for colloidal goldimmunochromatography qualitative detection reagents, aiming to provide reference for quality control andevaluation of production enterprises and inspection institutions, and eff ectively promote the quality level of such invitro diagnostic reagents. Method: Based on the quality standard requirements and classifi cation management ofcolloidal gold immunochromatography qualitative detection reagents, analyze the key performance elements of thistype of reagent quality, put forward corresponding suggestions, improve reagent quality. Results and Conclusion:Quality control and evaluation are the core elements that run through the entire product process. Membrane width,liquid migration speed, negative compliance rate, positive compliance rate, detection limit and repeatability are thekey performance indicators for quality control and evaluation of colloidal gold immunochromatography qualitativedetection reagents, which are crucial for the quality of reagents. Relevant production and R&D enterprises shouldreasonably design performance requirements and improve quality management systems, inspection agenciesshould conduct quality evaluations based on the key product performance points, regulatory authorities shouldaccelerate the revision of standards and strengthen post listing supervision based on industry and regulatory needs.Control these key performance indicators from various aspects of production, inspection, and supervision to improve the quality standards of reagents, so as to meet the clinical and regulatory needs.

Objective: To evaluate performance of BCR-ABL fusion gene testing kit by digital PCR methodusing BCR-ABL quantitative standard. Methods: The RNA of standard was extracted and its concentration andpurity was determined. The different BCR-ABL fusion gene testing kits (digital PCR method) and the digitalPCR instrument were used for detection. The molecular response of BCR-ABL fusion gene was acquired forquantitative standard. Results: The MR absolute deviation of accuracy standards WS2 and WS3 did not exceed± 0.5 log. The detection limit standard WS4 could be detected positive mutation in the BCR-ABL fusion gene.The MR coeffi cient of variation (CV) of repeatability standards WS1 and WS4 was less than 3.0%. Conclusion:The performance indicators of accuracy, detection limit and repeatability of BCR-ABL fusion gene quantitativetesting kits (digital PCR method) can all meet the requirements of Industry Standards for Breakpoint Cluster Region-Abelson Leukemia Virus (BCR-ABL) Fusion Gene Testing Kits, providing technical support for theimplementation of the standard.

Objective: To systematically elucidate the principles of clinical trial design of the companiondiagnostic devices (CDx) in our country, and to provide references for the clinical trials of related CDx. Methods:Based on the diff erent development models of CDx, the clinical trial designs of the original and non-original CDxdeveloped simultaneously with anti-tumor drugs in China were introduced. Combined with the considerationsduring the relevant product technical review, the science and rationality of the clinical trials design of CDx wereanalyzed in depth. Results and Conclusion: The CDx plays a very important role in the clinical application of theanti-tumor drugs. The clinical trials of the CDx and the clinical trials of anti-tumor drugs are closely related. Thereare multiple types of designs for clinical trials of this kind of products. Clinical trial main investigators shouldchoose the appropriate clinical trial designs based on the specifi c conditions of product development mode andproduct detection markers, which could evaluate the clinical signifi cance of the product more scientifi cally andreasonably, and promote the product to market as soon as possible.