Rare diseases are typically characterized by low prevalence, a wide variety, and severe conditions, most closely related to gene mutations. With the rapid development of biotechnology and artificial intelligence, advanced therapies such as gene therapy and cell therapy have brought new breakthroughs in the research and development of drugs for rare diseases. This article systematically reviews 15 orphan drugs approved by the CBER under the FDA in 2024—2025 from two dimensions: indications and treatment modalities, with a focus on the application, challenges, and future trends of advanced therapies such as CRISPR-Cas9 gene editing technology and organoid models in the field of rare disease drug development. Additionally, the current status of China's rare disease drug research and development is discussed.

Objective: To conduct a comparative analysis of oral dosage forms listed in the Pharmacopoeia of the People's Republic of China 2025 (ChP) and the International Pharmacopoeia 12th edition (Ph.Int.) to generate foundational evidence for optimizing dosage form monographs in the Chinese Pharmacopoeia, facilitating the inclusion of pediatric-appropriate formulations, and enhancing harmonization with international standards. Methods: A systematic literature review and side-by-side comparison were conducted to examine how each compendium names medicinal products and describes oral dosage forms; pediatric suitability was then scored against international and domestic quality criteria for child-appropriate formulations. Results: Compared with the ChP, the Ph.Int. embeds a formal nomenclature rule for drug products and appends explicit guidance on pediatric-appropriate formulations as well as minimum labelling/package-insert requirements-elements entirely absent from the current ChP. The ChP includes nine first-level categories encompassing 34 secondary oral dosage forms except traditional Chinese medicine preparations, whereas the Ph.Int. includes four first-level categories with 17 secondary oral dosage forms. Harmonization analysis revealed 12 dosage forms with concordant nomenclature and definitions; five with identical names but divergent definitions; 15 exclusively in ChP (7 with Ph.Int. mappings); and four exclusively in Ph.Int. (all mapped to ChP counterparts). When judged against international pediatric-usability criteria, 47% (8/17) of Ph.Int. oral monographs and 44% (15/34) of ChP entries are suitable for pre-school children or younger. Strikingly, three of the four Ph.Int.-only formulations demonstrate good acceptability for infants and toddlers, underscoring a ready opportunity for ChP expansion. Conclusion: ChP should draw on Ph.Int. experience to expand its general monographs, rationalize dosage-form classification, and expedite the inclusion of pediatric-friendly oral formulations for children under six. It is suggested to establish a joint working group composed of functional departments to enhance harmonization between the Pharmacopoeia and guidance policies/formularies for clinically commonly used medicines, improve public accessibility to drugs, and concurrently strengthen alignment with the International Pharmacopoeia.

With the rapid advancement of stem cell therapy, its application in clinical medicine has expanded significantly, posing new challenges to existing regulatory frameworks. This article systematically reviews the regulatory models for stem cell therapy across multiple countries, and based on a comparative analysis of regulatory policies, technical guidelines, and peer-reviewed literature, summarizes the major approaches and common trends regarding risk stratification, access pathways, and lifecycle quality management. The analysis highlights the widespread adoption of risk-based classification and accelerated access mechanisms to balance efficacy and safety. Through comparative analysis, the article details the evolution of China's regulatory system for stem cell therapy, emphasizing the characteristics of the “dual-track” model-parallel management through drug-based regulation and clinical research filing. In response to current issues such as unclear classification, fragmented oversight, and insufficient international alignment, the article proposes five key strategies: establishing scientific classification standards, improving quality control systems, facilitating clinical translation, strengthening ethical oversight and information transparency, and deepening international cooperation. These recommendations aim to support the development of a scientific, standardized, and efficient regulatory framework with Chinese characteristics, while also offering insights for global regulatory practices.

mRNA therapeutics have emerged as a promising platform in treating a wide range of diseases, including cancers, infections, genetic disorders, and autoimmune diseases. This article reviews the current development status of mRNA vaccines, existing challenges, relevant guidelines for nonclinical evaluation, and key focuses of nonclinical safety evaluation. Nonclinical research should focus on proof of concept, administration routes, species selection, and toxicity characteristics (such as inflammatory responses, hepatosplenic toxicity, and immune responses). This article systematically summarizes the research progress and safety evaluation strategies of mRNA vaccines, providing important references for future studies.

Immune checkpoint inhibitors (ICIs) are the core of tumour immunotherapy, but they are prone to induce immune-associated adverse events (irAEs). ICIs-associated enterocolitis is the most common and important irAE in the gastrointestinal tract, accounting for 37% of the fatal irAEs, which seriously affects the treatment and prognosis of patients. The incidence varies by drug: 7.7%~15% for cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, 1%~2% for programmed death-ligand 1(PD-1/PD-L1) inhibitors single therapy, rising to 13.9%~40% for combination therapy. The time of onset is earlier for CTLA-4 inhibitors (1~3 months) and later for PD-1/PD-L1 inhibitors (3~6 months). Risk factors include high-dose ICIs, combination therapy, previous history of IBD, intestinal dysbiosis, NSAIDs use, and genetic polymorphisms. Clinical manifestations are centered on diarrhiea, which can lead to complications such as intestinal perforation. The diagnosis is multifactorial, with biomarkers such as fecal calproteatin being important. The treatment is graded, with biologics improving difficult-to-treat cases, and the majority of patients with enterocolitis have a better prognosis.

Objective: To summarize the information-based initiatives for collaborative medical products administration promoted by international organizations, with the aim of further clarifying internationally accepted administration rules, supporting the expansion of openness and cooperation in the pharmaceutical industry, and further advancing the empowerment of regulation through information technology. Methods: A combination of website and literature research was used to review the policies and actions of international medical products administration organizations, including the Identification of Medicinal Products (IDMP) and Pharmaceutical Quality Knowledge Management (PQKM). Results: Two core initiatives of international collaborative information-based administration for medical products: the IDMP standard and its application scenarios, and the IDMP-based PQKM system, were identified. The implementation progress in the countries and regions such as the United States and the European Union was also summarized, as well as the pilot outcomes of the International Coalition of Medicines Regulatory Authorities (ICMRA). Conclusion: The study proposes implications and recommendations for the informationization department of national medical products administration, including continuous attention to international development, coordinated management of development and data security.

With the deepening of drug review and approval reform and the rapid development of digital technology, it is of great significance to enhance the application of drug review data, as an important basic resource in the field of drug review, for the efficiency improvement and mode transformation of drug review. Based on the European drug regulatory data, this study analyzed data strategy, data quality, data protection, and data application, and proposed ideas on high-quality data management system, data application value release, and stakeholder collaboration mechanism, in order to provide references for the research and application of drug review data in China, promote the value release of data elements, and assist in the high-quality development of drug review digitalization and intelligence.

Objective: To optimize the extraction process for the modified new formulation of Compound Nanxing Zhitong Plaster. Methods: Pharmacological effects were evaluated using adjuvant-induced arthritis rat models and acetic acid-induced writhing mouse models, while skin irritation was tested in rabbits. The differences in efficacy and skin safety between two extraction methods (FFNX-1: ethanol-water-ethanol extraction; FFNX-2: percolation+ethanol extraction) were compared. Active ingredient contents (including aconitine, eugenol, etc.) and dry extract yield were used as indicators to optimize extraction parameters through orthogonal experimental design. Results: FFNX-2 (percolation+ethanol extraction) exhibited optimal anti-swelling, anti-inflammatory and analgesic effects, along with lower skin irritation in rabbits, establishing it as the optimal extraction process for the improved new drug formulation of Compound Nanxing Zhitong Plaster. Conclusion: The optimized extraction parameters were as follows: Six herbs including Caryophylli Flos extracted three times (1 h each) with 4 volumes of 50% ethanol; Arisaematis Rhizoma and Aconiti Radix extracted by percolation with 70% ethanol (particle size 2~5 mm, soaked for 24 h, flow rate 1 mL·min^－1·kg^－1, collecting 8 volumes of effluent). The optimized extraction process effectively retains active components while reducing toxicity risks, providing a scientific basis for the modern development of Compound Nanxing Zhitong Plaster.

Objective: To investigate the therapeutic effect of MQZZJ (total alkaloids of Strychnos) on experimental autoimmune myasthenia gravis (EAMG) rats and to elucidate its underlying mechanisms. Methods: The EAMG rat model was established by immunizing female Lewis rats with the R97-116 peptide fragment. Rats were assigned to different groups and treated with MQZZJ (0.35, 0.7, and 1.4 mg·kg^－1) or prednisone (4.2 mg·kg^－1). The therapeutic effects and potential mechanisms were evaluated by monitoring the Lennon score and rotarod falling speed, measuring serum levels of acetylcholine receptor antibody (AChR-Ab), IgG, IgG1, IgG2b, IFN-γ, IL-17, and TGF-β, and detecting the CD4⁺/CD8⁺ ratio in peripheral blood lymphocytes. Results: MQZZJ significantly reduced the Lennon score, increased the rotarod falling speed, and reduced  serum levels of AChR-Ab, IgG, and the IgG2b subtype. It also significantly decreased serum IL-17 and IFN-γ levels, increased serum TGF-β levels, and reduced the CD4⁺/CD8⁺ ratio. Conclusion: MQZZJ can markedly ameliorate myasthenic symptoms in EAMG rats. The mechanism may be related to inhibiting AChR-Ab production, reducing the CD4⁺/CD8⁺ ratio, modulating immune dysfunction, and alleviating abnormal inflammation.

Objective: To investigate the effects of Danggui Buxue Decoction (DBD) on the nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4 pathway, degree of lipid peroxidation, and synaptic plasticity of rats with vascular dementia (VD) induced by bilateral common carotid artery ligation (2-VO). Methods: Sixty male SPF grade SD rats were randomly divided into sham surgery group, bilateral common carotid artery ligation VD model group, low-dose 2-VO+DBD group, medium dose 2-VO+DBD group, high-dose 2-VO+DBD group, and 2-VO+donepezil group, with 10 rats in each group. After 24 hours of modeling，continuous administration was performed for 4 weeks and samples were collected. The Morris water maze experiment and the dark avoidance experiment were used to evaluate the influence on the learning and memory ability of rats. The lipid peroxidation level was detected using a kit，and the morphology of hippocampal neurons was observed using Nissl staining. The expression of hippocampal neurons was observed using immunofluorescence staining, and the expression of pathway and synaptic plasticity-related proteins was detected using Western blotting. The mitochondria and synaptic ultrastructures of hippocampal neurons were observed using transmission electron microscopy, and the morphology and density of dendritic spines of hippocampal neurons were observed using Golgi staining. Results: The Morris water maze experiment and the dark avoidance experiment demonstrated that DBD could enhance the learning and memory abilities of rats. The results of Nissl staining and immunofluorescence showed that after DBD administration, the number of hippocampal neurons in the VD model group of rats increased, the expression rate of Nrf2 increased, and the neuronal damage was improved. VD rats showed a decrease in GSH levels, an increase in lipid peroxide and 4-hydroxynonenal levels, and DBD administration could alleviate oxidative stress. In VD rats, the expression of NAD(P)H quinone dehydrogenase 1, GPX4, Nrf2, postsynaptic density protein 95, Synapsin1, and brain-derived neurotrophic factor proteins decreased, and all of these significantly increased after administration of high dose DBD. Transmission electron microscopy and Golgi staining showed that DBD could improve the mitochondrial structure and synaptic ultrastructure of neurons, and increase the density of dendritic spines. Conclusion: DBD can exert a neuroprotective effect and improve the learning and memory abilities of VD model rats by regulating the Nrf2/GPX4 signaling pathway, inhibiting neuronal lipid peroxidation, and enhancing synaptic plasticity.

Objective: To conduct a comprehensive clinical evaluation of albutrepenonacog alfa (rIX-FP) for the treatment of hemophilia B. Methods: Based on guidelines, literature, and publicly available data, and following the PICOS principle, rIX-FP was compared with plasma-derived FIX, standard half-life recombinant FIX (SHL rFIX), and extended half-life recombinant FIX (EHL rFIX) across five dimensions: efficacy, safety, suitability, innovation, and economy. Results: The evaluation results indicate that rIX-FP has potential advantages over other FIX preparations in terms of reducing the annualized bleeding rate, increasing the proportion of patients with zero bleeding events, and improving joint health, with consistent trends observed in the pediatric subgroup. The safety profile of rIX-FP is comparable to that of other recombinant FIX preparations, with no unmanageable safety risks observed. Regarding suitability, rIX-FP is available in five dosage specifications, offers flexible dosing options, and requires no special storage conditions. In terms of innovation, it utilizes albumin fusion technology to extend the half-life, thereby reducing dosing frequency and increasing trough levels. As for economy, although not yet marketed in China, international data suggest that long-term treatment (≥3 years) with rIX-FP has a cost advantage compared to SHL rFIX and rFIXFc. Conclusion: Based on available evidence, rIX-FP demonstrates certain clinical advantages in the treatment of hemophilia B. However, head-to-head comparative studies and local pharmacoeconomic evaluations are still warranted.

Objective： To systematically evaluate the efficacy and safety of histone deacetylase inhibitors (HDACi) combined with exemestane compared with exemestane alone in the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Methods： Electronic databases including PubMed, Cochrane Library, Embase, Wanfang Data, CNKI, and VIP were searched for randomized controlled trials (RCTs) comparing HDACi combined with exemestane versus exemestane alone in the treatment of HR+/HER2- breast cancer. The search period began from database inception to July 10, 2025. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was performed using RevMan 5.4.1 software. Results： Five RCTs involving 1 588 patients were included. The meta-analysis showed that HDACi plus exemestane group had significantly better progression-free survival [HR=0.77, 95%CI (0.67, 0.89), P=0.000 2], objective response rate [OR=1.69, 95%CI (1.15, 2.50), P=0.008], and clinical benefit rate [OR=1.39, 95%CI (1.05, 1.85), P=0.02] than the exemestane alone group. However, there was no significant difference in overall survival between the two groups [HR=0.91, 95%CI (0.63, 1.30), P=0.60]. Regarding safety, the meta-analysis showed that the overall incidence of ≥grade 3 adverse events was significantly higher in the HDACi plus exemestane group compared to the monotherapy group [OR=7.16, 95% CI (4.37, 11.74), P<0.000 01]. Conclusion： Current evidence suggests that in HR+/HER2- breast cancer patients, HDACi combined with exemestane significantly prolongs progression-free survival and improves objective response rate and clinical benefit compared to exemestane alone, but also significantly increases the risk of ≥grade 3 adverse events, particularly hematological toxicity and fatigue. Clinicians should carefully weigh the benefits of efficacy against the risks of adverse events when making decisions.

Objective: To analyze the clinical features and risk factors of tirzepatide-associated ketoacidosis using real-world data, thereby providing evidence for safer clinical use. Methods: A systematic literature search was conducted in both Chinese and English databases from inception until August 31, 2025, to identify case reports on tirzepatide-induced ketoacidosis. Data were also extracted from the FDA Adverse Event Reporting System (FAERS) spanning January 2004 to June 2025. Disproportionality analysis using the reporting odds ratio (ROR) was employed for signal detection, and descriptive statistics was applied to summarize the demographic, clinical, treatment, and outcome variables. Results: Fourteen published case reports and 229 cases from the FAERS were included. A higher proportion of cases occurred in females (78.57% in case reports; 51.96% in FAERS). Ketoacidosis often developed early during treatment (median time: 5 weeks), with common clinical features including nausea, vomiting, abdominal pain, dehydration, and metabolic acidosis. Significant signals were detected linking tirzepatide to various forms of ketoacidosis, particularly starvation ketoacidosis (ROR=107.36, 95%CI: 71.75~160.63) and euglycemic diabetic ketoacidosis (ROR=3.52, 95%CI: 2.51~4.93). Concomitant use of sodium-glucose co-transporter 2 inhibitors (SGLT-2i) was most frequently reported (52 cases). Most patients recovered after drug discontinuation and supportive care, although four fatal cases were documented in FAERS. Conclusion: Tirzepatide is associated with a significant risk of ketoacidosis, particularly in female patients, non-diabetic state, and those using SGLT-2i concurrently. Enhanced vigilance, patient education, and early intervention are recommended to mitigate the risk of serious metabolic adverse events.