Objective: To analyze the related substances produced in new production process of somatostatin, and the stability of raw materials and preparation was studied. Methods: The related substances were separated, collected, characterized and analyzed by high performance liquid chromatography, preparative liquid chromatography and ultra performance liquid chromatography-time-of-flight mass spectrometry tandem system. In addition, the stability of somatostatin and its preparation was studied under high temperature, light, oxidation and acidolysis destruction conditions. Conclusion: Based on the stability study combined with the production process of somatostatin and its preparation, somatostatin will produce new impurities in the new production process. This study provides a basis for revising pharmacopoeia standards.

Objective: To develop the determination method of the contents of 3′-hydroxy puerarin, puerarin, puerarin apioside, narirutin, naringin, hesperidin, neohesperidin, and praeruptorin A in Shensu Ganmao tablets (SGT) using high performance liquid chromatography with two-reference multi-component method (TRMC). Methods: The analyses were performed on an Agilent ZORBAX SB-C₁₈ column (250 mm×4.6 mm, 5 μm) using the mobile phase of 0.1% phosphoric acid-acetonitrile in gradient elution mode at a flow rate of 1.0 mL·min^-1. The detection wavelength was 283 nm. Results: Taking puerarin as internal reference, the RCF of 3′-hydroxy puerarin and puerarin apioside are 0.853 and 1.354. Taking naringin as internal reference, the relative correlation factors (RCF) of narirutin, hesperidin, neohesperidin, and praeruptorin A are 1.181, 1.027, 1.002, and 2.188. The RCF showed validated on different experimental conditions. The results of 8 components in SGT were in acceptable limits by using TRMC and the external standard method (ESM). Conclusion: The newly established TRMC can determine the characteristic constituents in Puerariae Lobatae Radix, Citri Reticulatae Pericarpium, Aurantii Fructus, and Peucedani Radix in SGT simultaneously, which can be used for quality control of SGT.

Objective: To summarize the evaluation of meta analyses on the correlation between short-term endpoints (ORR, CR, etc.) and final endpoints (PFS, OS) in cancer, and to explore the correlation between different types of cancer. Methods: Based on Cooper et al. (2020), a systematic search in databases of Medline, Embase, the Cochrane library, Web of Science, and CINAHL were updated from March 2019 to January 2022. Meta analyses assessing the individual-level and trial-level correlation between short-term intermediate endpoints and final endpoints are summarized, and subgroup analyses are conducted in terms of the three most common cancer types. Results: The systematic review includes 77 studies across 20 types of cancer, in which non small cell lung cancer (NSCLC), colorectal cancer (CRC), and breast cancer are the three most common cancer types. The included studies mainly analyzed the correlation between ORR and OS (91%) or PFS (35%), and the correlation was week regardless of individual-level and trial-level. In subgroup analyses, over half studies in NSCLC indicated good or excellent trial-level correlation between ORR and PFS (R²>0.4). Also, most studies in NSCLC and CRC indicated that the trial-level correlation between ORR and PFS >0.3, >0.2) was stronger than that between ORR and OS (>0.1, >0.1). Conclusion: The short-term intermediate endpoints, such as ORR, may not be good surrogates for final endpoints. ORR may be a short-term intermediate indicator worth be noticed by regulators, which could be surrogate for PFS in trial-level in the field of NSCLC and CRC, especially in the field of NSCLC.

Objective: To mine the security alert signals of neratinib based on the FDA Adverse Event Reporting System (FAERS) database to provide a reference for the safety of clinical medication. Methods: The adverse drug event (ADE) signals data of neratinib from the FAERS database from the third quarter of 2017 to the third quarter of 2021 were collected. The data mining was performed using the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) in the proportional imbalance method. Results: A total of 1 362 ADE reports with neratinib as the primary suspected drug were collected, and 96 neratinib ADE signals were mined; 71 signals were obtained after excluding non-adverse drug reaction signals, involving 13 systems. Among them, a total of 48 new signals were not mentioned in the instructions, accumulating 12 systems. Gastrointestinal disorders ADE entries totaled 2 186 cases, generating 25 signals; new signals from investigations accounted for 85.71% of their total system signals. Daily dose was not an independent risk factor for the occurrence of gastrointestinal disorders and investigations ADE. Logistic regression results showed that a course of treatment ≤7 days was an independent risk factor for the occurrence of gastrointestinal disorders, with statistically significant results (P=0.008); compared to a course of treatment ≤7 days, a course of treatment 1 to 3 months was an independent risk factor for the occurrence of investigations ADE (OR=4.288, 95% CI of 1.342 to 13.703;P=0.014). Conclusion: No matter what daily dose is used, adverse reactions need to be paid attention to. The duration of medication is of great significance to the risk of adverse reactions of neratinib, and pharmaceutical care should be strengthened during clinical medication.

There is high similarity between real-world study (RWS) and the clinical practice of traditional Chinese medicine (TCM). RWS can be used as one of the methods to collect the empirical data of human use normatively, and generate high-quality empirical evidence of human use of TCM. From the perspective of the whole life cycle of TCM, RWS can not only help to choose the subject and set up the project, optimize the strategy of TCM research and develop (R&D), shorten the R&D period, guide the pharmacological and toxicological research and clinical trial design, improve the research efficiency, but also continuously explore the clinical value and extend the life cycle of products. In view of the deficiencies in the quality of real-world data and the methodology for using real-world data needing to be standardized, it is necessary to clean up the data to form applicable analysis data, and form the truth through standardized methodological design, well organized implementation, and reasonable statistical analysis. Exploring the safety and effectiveness of TCM with the real-world evidence would support the research and development of new TCM products with human experience.

This paper analyzed the situation of patent applications of anti-tumor traditional Chinese medicine (TCM) in China in order to provide suggestions for the research, development, utilization and innovation of anti-tumor TCM. The Patentics patent database was used as the data source to search and analyze the patent application of anti-tumor TCM in China. The patent applications of anti-tumor TCM in China mainly experienced three stages: steady development (2000—2012), rapid outbreak (2013—2015) and slowing down (2016-present). However, the quality of patent applications showed an opposite trend, resulting in a low patent effective rate (21%). The quality of the patents applied by modern pharmaceutical enterprises and universities showed a higher level. The patent applications of pharmaceutical enterprises mainly focused on the extract of TCM and preparation process, while universities mainly focused on TCM composition and compound preparations. In an overall view, the patent application quality of anti-tumor TCM in China is relatively low, we should improve the patent quality, learn from the foreign patent layout experience, enhance the ability of university-enterprise collaborative innovation, and promote the inheritance and development of TCM.

The research and development process of osimertinib was prompted by new drug expedited programs in the US, which resulted in the highly coincident time periods of drug registration and patent examination. Based on the review of the research and development process and patent strategy of osimertinib, the opportunities and challenges of pioneering new drugs and follow-on drugs under the global trend of accelerating approval process were analyzed. The exploration of special patent examination management such as creating a fast-track for drugs undergoing clinical trials was proposed to strengthen the protection of innovations.

According to the spirit of the “implementation opinion on comprehensive strengthening of the drug regulatory capacity construction” issued by the General Office of the State Council, this article aimed to provide reference for the evaluation benchmark and future direction for the improvement of drug evaluation ability under the strategy of pharmaceutical power. According to the dual organization theory, lessons were drawn from WHO and EMA competence assessment for regulatory authorities, and the drug evaluation ability model was constructed by using two rounds of expert investigation method of Delphi. The drug evaluation ability model was composed of input, process control and output modules, which contained 16 primary indicators of core competency assessment and 58 secondary indicators altogether. It will provide a basis for the assessment of the ability of drug review authority in China in the new period, to find the gap between vision and reality, to improve the ability of drug review from the long-term goal, and to promote the capability development of drug review authority.

Novel designs for early clinical trials of anticancer drugs have received widespread attention and have been applied in drug development. This paper introduced three methods, i.e., algorithm-based designs, model-based designs and model-assisted designs, in single-dose exploration and multiple-dose exploration respectively. Their basic ideas and statistical methods were introduced and then their strengths and weaknesses were explained. These novel designs can not only reduce R&D costs and research time but also determine whether the medicine is effective in clinic earlier, thereby increasing the development efficiency.