Caffeine is the drug of choice for the treatment of apnea of prematurity. Although it has been used abroad for nearly 50 years, it has only begun to be widely used in China in recent years. There is still no consensus on the timing of caffeine initiation and discontinuation at home and abroad up to now. The efficacy and safety of caffeine under the standard-dose regimen have been confirmed, but the apnea symptoms of some preterm infants are still poorly controlled. The high-dose regimen is more effective, but the potential adverse effects are still worrisome. In addition, the necessity for the therapeutic drug monitoring of caffeine remains debatable since the effective blood concentration range is still controversial. Therefore, the pharmacokinetic characteristics of caffeine in premature infants, as well as the efficacy, safety, and effective blood concentration range under different dosage regimens were summarized. Of note, the research progress of the therapeutic drug monitoring and dose regimen optimization of caffeine were also discussed.

As the use of cell therapy products such as chimeric antigen receptor T cells (CAR-T) is getting matured, there has been an increasing interest in the methods used to test the quality of cell therapy products. In vitro viability assay is an important method for evaluating the effectiveness of cell therapy products and is also widely used in the product release process because of its simplicity and rapidity. In this paper, we review the in vitro potency determination methods for cell therapy products such as CAR-T from the perspective of both effector cells and target cells.

Objective: To explore the effective compatibility ratio of the 5 main active ingredients in Gardenia and Panax notoginseng by uniform design test method thus to provide preliminary experimental evidence for clinical treatment of Alzheimer's disease. Methods: A model of SH-SY5Y cell injury induced by β-amyloid (Aβ_1-42) was established, and the cell survival rate was used as an indicator to study the effective concentrations of the main active ingredients against Aβ_1-42-induced SH-SY5Y neuronal injury, and according to the damage recovery rate, five ingredients with better efficacy were selected. On this basis, the five components with good efficacy were used as independent variables X₁, X₂, X₃, X₄ and X₅, respectively, the injury recovery rate (%) as the dependent variable Y, U₂₁ (21⁵) uniform design table and 2 mathematical models of linear and quadratic polynomials were selected, and the variables were screened by stepwise regression method to determine the effective compatibility ratio of the 5 active ingredients. Results: The main active components of Gardenia-Panax notoginseng, except genipin, could increase the cell survival rate of SH-SY5Y cells induced by Aβ_1-42 in a concentration-dependent manner. 5 ingredients with good efficacy were identified as notoginsenoside R1, ginsenoside Rb1, ginsenoside Rg1, geniposide, and genipin gentiobiglycoside. The results of uniform design experiments were obtained by regression analysis and Y=12.775 019 92-0.493 827 042 7X₂+0.070 634 665 58X₁X₂-0.022 126 968 533X₁X₅+0.053 000 691 95X₃X₄ (r=0.857 4, F=11.105 9, P=0.002), and the uniform design test verified that the best combination ratio was notoginsenoside R1∶ginsenoside Rb1∶ginsenoside Rg1∶geniposide∶genipin gentiobiglycoside=1∶1∶1∶1∶0. Behavioral experiments showed that compared with the model group, the number of tests and memory errors of donepezil hydrochloride group and gardenia-Panax notoginseng optimal matching were significantly reduced. The results of ROS and Western blot showed that compared with the model group, the optimal combination of donepezil hydrochloride group and gardenia-Panax notoginseng could effectively reduce the fluorescence intensity of ROS and the expression of RAGE protein. Conclusion: The optimal matching ratio obtained by uniform design screening can effectively improve Alzheimer's disease, and its mechanism of action may play an anti-Alzheimer's effect by inhibiting the activation of RAGE-ROS pathway, which provides an experimental basis for the treatment of Alzheimer's disease.

Based on the new changes in the definition of falsified and substandard drugs and the new requirements for their identification in newly revised "Drug Administration Law" and "Interpretation for Handling the Criminal Cases Endangering Drug Safety", this paper discusses a new working mode for the detection of falsified and substandard drugs. In the new working model, the detection of falsified and substandard drugs can be classified into two kinds: to need and not to need the support of testing results. If testing is needed, three factors should be considered, i.e., the implementer of testing, testing capability, and presentation of testing result. The paper cited two typical examples taking place respectively in 2006 and 2015 to elaborate how testing result supported the detection of falsified and substandard drugs, one is about illegally adding diglycol in injection, another is about adulterated Ginkgo biloba leaves and their extracts. In order to improve the quality and efficiency of the detection of falsified and substandard drugs and optimize the utilization of drug testing resources, the testing of falsified and substandard drugs under the new requirements should be based on the needs of the identification, with the goal of supporting the drug regulatory department to issue the identification opinion about the falsified and substandard drugs. The model will change the traditional understanding on the role of drug testing results in supporting the confirmation of falsified and substandard drugs, to delink the connection between detection and testing, making the testing result not the precondition for the confirmation of falsified and substandard drugs. In order to implement the new work mode, drug regulatory authorities at prefecture level and above need to clarify the identification of whether inspection support is needed according to the laws, national and provincial drug inspection institutions need to establish a division of labor and cooperation mechanism that matches the regulatory functions, and drug testing institutions need to clarify the requirements for samples, standards for testing, and testing conclusion.

In 2022, the heat index of the whole biomedical industry gradually declined, but the hot track such as gene therapy and cell therapy remains active. Source technology breakthroughs and multidisciplinary cross-integration innovation have accelerated the process of new drug development. There are a rich variety of new drugs approved in 2022, and some blockbuster new drugs and new technology therapies have brought new therapeutic hope for complex diseases. The Center for Drug Evaluation and Research (CDER) of the US FDA approved 37 innovative drugs in 2022, 25 of which were first approved worldwide. The European EMA approved 51 innovative medicines throughout the year, 8 of which were first approved worldwide. Japan's Pharmaceutical and Medical Device Agency (PMDA) approved 48 new drugs throughout the year, 12 of which were first approved in the world. The National Medical Products Administration (NMPA) of China approved 40 new drugs throughout the year, 11 of which were first approved worldwide. This paper summarized the new drugs approved for market in the US, EU, Japan and China in 2022, and provided an outlook on new drug development and biopharmaceutical development trends in 2023.

The intake of food could lead to various changes in the physiology of human gastrointestinal tract, such as the pH of the gastrointestinal, ionic strength, buffer capacity, the time of gastric emptying, visceral blood flow, and the metabolizing enzymes. These physiological changes would have effects on the release, absorption, distribution, metabolism, and/or excretion of a drug, leading to changes in its pharmacokinetics. Therefore, it is of great importance for clinical research and prediction of the food effect on novel drugs to understand the manner of change in the luminal condition of human gastrointestinal caused by food intake, as well as the manner of the effect on bioavailability. In this paper, we summarized the clinical trials about the food effect on drugs in clinical trial databases and literature first. Then, the guidelines relevant to clinical trials on food effect issued by the National Medical Products Administration (NMPA) of China, the United States FDA, and EMA were compared and summarized. Finally, taking the antitumor novel drugs as an example, we summarized and analyzed the clinical trials about food effect registered in China in the past 10 years, focusing on the main factors related to the food effect in the development of novel drugs, the official guidelines, as well as the current status of research in China, aiming to provide basic research data about the food effect for the development of novel drugs in China.

The novelty examination of pharmaceutical crystal patents often requires the use of legal presumption as a method of finding out the facts. The process is complex because it involves the allocation and transfer of the burden of proof, the refutation and overturn of the presumed facts, and the use of legal techniques in the investigation of technical facts. Through typical cases, this paper compares the differences among different examination procedures in the judgment of evidence that is sufficient to challenge the novelty of pharmaceutical crystals and shift the burden of proof, and explores the reasons for the differences from the perspectives of the uncertainty of crystal acquisition, the purpose and value of the setting of substantive examination and invalidation procedures, the legal status of patents (applications), the burden of proof and the standard of proof, and further analyze the impacts of the presumption methods of different examination procedures and the performance of the parties' request and rebuttal on the grant and stability of the pharmaceutical crystal patent.

The product production chain of traditional Chinese medicine suffers from low product quality, low efficiency transformation, and insufficient innovation capability, and there lacks complete innovation process chain to address product-independent R&D innovation. For the process chain of Chinese medicine product development, this paper analyzes and discusses the application of Chinese medicine product innovation methods by combining five methods: quality function development (QFD), inventive problem solving theory Teoriya Resheniya Izobreatatelskikh Zadatch (TRIZ), quality by design (QbD), design of experiments (DOE), and data envelopment analysis (DEA). Firstly, QFD is applied to determine the direction of innovation by comprehensive analysis of user needs and actual situation; secondly, TRIZ is applied to analyze and solve the contradictions to be solved by the product, propose solutions and combine QbD and DOE for experimental design and verification; finally, DEA is applied to allocate resources to optimize the efficiency. Combining innovation methods to develop and design Chinese medicine products can develop core technologies and equipment with independent intellectual property rights, effectively improve the quality and effectiveness of Chinese medicine products transformation, which is meaningful for the development of Chinese medicine products.

Patents have long been considered as the most important way to protect pharmaceutical innovations, and the drug patent system has exerted a profound impact on the development of the pharmaceutical industry. In the context that domestic effective drug regulations and patent laws and regulations have covered the provisions on drug patent linkage system, this paper, by taking the first case of domestic drug patent linkage litigation as an instance, analyzes the trial effect of the newly launched drug patent linkage system in China, explores its impact on the generic drug industry, and tries to give suggestions to generic drug enterprises on the choice of patent application types and the authenticity of application materials. The research-based pharmaceutical enterprises need to seize the opportunity to safeguard their rights and protect themselves against patent infringement by choosing an appropriate method to resolve patent disputes. Moreover, given the constraints of China's binary separation of procedures of patent infringement and patent invalidation on the early solution of pharmaceutical patent disputes and the problems awaiting to be solved in different types of patent applications, this paper also puts forward related suggestions on patent protection, including the necessity of timely review and analysis of the implementation of the patent linkage system, enhancement of the legal status of administrative adjudication to enable some authorities of administrative confirmation, and the necessity for clearer definition of types of patent applications and further standardization of patent infringement cases under different circumstances.