During the past ten years, the research and development of new drugs for skin diseases have boomed. The new drugs including biologics and small molecules have rapidly developed and greatly improved the treatment of common inflammatory/immunological skin diseases. More than 200 clinical trials have been performed and many new drugs was approved in China, bringing the dermatological treatment to a new era. In this paper, recent progress was reviewed in new drug development on psoriasis, atopic dermatitis, alopecia areata and androgenetic alopecia in China.

As a sensor of environment-cell interaction, aryl hydrocarbon receptor (AhR) plays an important role in maintaining barrier function, immune system and antioxidant process of the skin. AhR regulates the expression of many genes that are related to basic skin functions. It is expressed in all types of skin cells and involved in the progression of a variety of inflammatory skin diseases, including atopic dermatitis and psoriasis. Due to the complexity of the AhR protein structure, its crystal structure has not been successfully resolved until researchers obtained the crystal structure of indirubin binding to HSP90-XAP2-AhR complex recently. Clinical studies have shown that activation of the AhR pathway by ligands is of significance to the treatment of inflammatory skin diseases, as demonstrated by the clinical success of an AhR agonist, Benvitimod, for the treatment of psoriasis. This article presents a brief review on the role of AhR in inflammatory skin diseases and the current progress in drug development.

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.

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.

Objective: To conduct a research on the current difficulties in the design, evaluation, and implementation of clinical trials of pediatric Chinese medicine and build a list of questions for the development of the Expert Consensus on Issues Related to Clinical Trials of Pediatric Chinese Medicine. Methods: The parties involved in clinical trials of pediatric Chinese medicine were surveyed by online questionnaires to learn the difficulties in the design, evaluation, and implementation of clinical trials. Results: A total of 49 questionnaires were collected, and the experts believed that it was difficult to determine the indications, test purpose, diagnostic criteria, age range, control drugs, efficacy and safety evaluation in the design and evaluation stage of clinical trials of traditional Chinese medicine for children, and there was a lack of scientific basis for developing medication regimen. In the implementation phase, the start time of the trial should be specified, and further improvement should be made in the aspects of ethical review, subject recruitment, informed consent, compliance, and DMC setting. Conclusion: There were many difficulties in the design, evaluation, and implementation of current clinical trials of pediatric Chinese medicines, which should be improved from various aspects such as policy, awareness, and technology, thus to promote the research and development of pediatric proprietary Chinese medicines.

Oil APIs for injection extracted from animals and plants mainly used in fat emulsions. Based on the requirements of relevant regulations, guidelines, and review experience in recent years, this paper expounds some considerations on the study of oil APIs for injection extracted from animals and plants, including starting materials and process control, impurity control, validation of virus inactivation/removal process, quality research, etc, in order to provide some references for future research．

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.

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.

Objective: To observe the effect of Xiangpishengji Ointment on the wound surface model of small Bama pigs, preliminarily observe the effect of Xiangpishengji Ointment on the VEGF-Notch signaling pathway in the wound surface of experimental pigs, compare the difference in wound healing between experimental pigs and rodents, and explore the rationality of selecting experimental pigs for the development of wound surface model. Methods: A total of 48 sores were prepared on the back of 4 small Bama pigs and divided into 2 groups, namely the Conwell hydrogel group and the Xiangpishengji Ointment group. Photos were taken on the 0, 7 and 14 days after surgery. Image J software was used to measure the wound area, calculate the wound healing rate, record the wound healing time, and observe the pathological changes with HE staining. The expression of VEGF-Notch signaling pathway related factors in wound tissue was detected by immunohistochemistry. Results: Xiangpishengji Ointment could promote the wound healing of experimental pigs, improve the wound healing rate, shorten the healing time, and promote the expression of VEGF-Notch signaling pathway related factors. Conclusion: Xiangpishengji Ointment can promote the healing of small Bama pig wound model, which may be related to the influence on VEGF-Notch signaling pathway. Experimental pigs are more similar to humans than rats in physiological and pathological aspects, and may become an accurate model for wound healing exploration in the future.

Objective: To study the stability of hepatocyte growth-promoting factor for injection (HGFI) and its compatibility with different material infusion sets by physical and chemical testing and cell experiment. Methods: HGFI was dissolved with different solvents. Then the solution was sampled at 0 h and 24 h with or without infusion tube made of polyvinylchloride (PVC), thermoplastic elastomer (TPE), of thermoplastic polyurethanes (TPU) to determine the pH value, protein, clarity, visible foreign bodies, insoluble particles, osmolarity, content and macromolecular substances. HGFI was dissolved with 5% glucose injection or normal saline for 0 h and 24 h, and then diluted with complete medium and co-incubated with rat liver cells (BRL) for 48 h. The cell viability was detected by CCK-8 method. Results: The pH value, protein, degree of clarification, visible foreign bodies, insoluble particles, osmotic molar concentration, content determination, and macromolecular substances of HGFI dissolved with 5% glucose, normal saline, 5% glucose and normal saline and sampled via/not via infusion tube of different materials (PVC, TPE, TPU) at 0 h and 24 h all met the requirements of 2020 edition of Chinese Pharmacopoeia. Compared with the normal control group, HGFI solutions at 0 h and 24 h not only had no toxic effects on BRL cells, but also significantly increased the viability of BRL cells. Conclusion: HGFI is stable within 24 h with different solvents and has good compatibility with infusion sets of different materials. Moreover, it keeps wonderful bioactivity within 24 h.