The rapid development of cell and gene therapy products carries the high expectations of industry, patients, and healthcare workers, and also poses a considerable challenge to drug regulatory authorities. In order to promote the development and marketing of these products with great therapeutic potential, the US and European drug regulatory authorities have adopted measures to adjust organizational structures, improve regulations and guidelines, and develop targeted accelerated procedures for cell and gene therapy products. China's regulatory policy for cell and gene therapy products is also constantly improving. By summarizing and analyzing the accelerated assessment and approval policies of the US and European drug regulatory agencies for cell and gene therapy products, this paper aims to provide reference for the optimization of the accelerated assessment and approval policies for these classes of products in China.

Autologous chimeric antigen receptor T cell (CAR-T) cell therapy products have brought significant survival benefits to tumor patients, especially in the treatment of hematologic tumors. However, the common production mode of autologous CAR-T therapy products is complicated and has a long cycle. As a result, the production capacity of this kind of products has limited their clinical application to a certain extent. In this paper, based on the analysis of the common production mode of autologous CAR-T cell products, the content and evaluation of the capacity confirmation study and capacity change study of autologous CAR-T therapeutic products are proposed in combination with the current research progress, hoping to effectively promote the development and clinical application of such products.

As the continuous in-depth research on prophylactic mRNA vaccines, new questions have been raised about lipid nanoparticles in aspects of structures and morphologies. Based on the principle of ICH Q6B, the characteristics and changes of the structures of lipid nanoparticles were preliminarily discussed from the perspective of pharmaceutical evaluation, and the additional study for the structural characteristics were also addressed for providing a reference for the quality assessment and control of prophylactic mRNA vaccines.

As a critical part of the lifecycle management of biological products, post-approval changes may bring potential impact on the quality of biological products. Compared with other therapeutic products, prophylactic vaccines show different emphasis on regulatory requirements, product characteristics, manufacturing quality control, etc. so there are special considerations on the research and registration of post-approval changes. Aiming to help vaccine applicants increase knowledge about post-approval changes, the technical requirements on post-approval change of vaccine products and other biological products are compared and analyzed in this paper, and some special considerations for the study of post-approval change of vaccine are refined.

In order to enhance patient compliance, subcutaneous injection (SI) is one of the important directions for differentiated development of therapeutic recombinant protein drugs (TRPDs). This has resulted in a significant rise in clinical trial applications and license applications of biologics in recent years. As for SI products, there are some special considerations in the development of formulation, excipient quality control, product quality control and stability studies compared with those of intravenous administration dosage forms, which are due to the inherent properties of TRPDs and the potential impact of high concentration formulation on product quality and stability, as well as the application of special excipients, represented by hyaluronidase. This manuscript presents a summary of the application of TRPDs in SI dosage form since 2020, discusses the special considerations in the review of chemical manufacturing and control (CMC), and the possible challenges that arise in the R&D and manufacturing process of this type of products. The objective is to offer patients new TRPD products that are safe, effective, quality-controlled, and user-friendly through the collaborative efforts of sponsors and the regulatory authority by strengthening technical communication.

Glycoprotein hormones, including follicle-stimulating hormone, luteinizing hormone, chorionic gonadotropin, and thyroid stimulating hormone, are heterodimers consisting of non-convalently bound α and β subunits. Glycosylation complexity and structural heterogeneity are the focus of structural characterization and quality control of glycoprotein hormones. The modification sites, modification types, and sialic acid content of glycosylation are closely related to the receptor binding, signaling, biological function, and clearance rate of glycoprotein hormones in the body. In this paper, we summarize the marketed products of recombinant glycoprotein hormones, analyze the "macro" and "micro" complexity of glycosylation modification of these drugs, clarify the relationship between structural heterogeneity and biological function, sort out the analytical techniques used for structural confirmation and glycan chain identification, and put forward the relevant considerations of R&D pathway and CMC research based on their quality control difficulties.

With the expiration of the patent of denosumab (Prolia^®/Xgeva^®) and its marketing in China, the number of denosumab biosimilars developed by domestic biological enterprises according to the path of biosimilars is gradually increasing. This paper reviews the domestic and foreign registration and research status of the original drug and biosimilars, clarifies the challenges and technical requirements in the similarity evaluation of denosumab, analyzes and discusses the common problems in the pharmaceutical evaluation of denosumab biosimilars in combination with the review practice, in order to provide a basis for the pharmaceutical development and evaluation of denosumab biosimilars.

Neoantigens are a class of specific polypeptides produced by gene mutations in tumor cells, which can be expressed and processed in cells. They are subsequently presented to the cell surface by major histocompatibility complexes and recognized by T cells, thus activating the body's immune system and initiating a series of immune responses. Due to the rapid development of sequencing technology and artificial intelligence prediction methods, neoantigen-based tumor immunotherapy has emerged as a promising approach for future cancer treatment. In the era of precision medicine, neoantigen-based personalized tumor vaccines and adoptive T cell transfer therapy have shown encouraging results in the treatment of malignant melanoma, brain glioma and other tumors. Furthermore, the combination of neoantigens with other immunotherapies shows significant potential for application. However, as a new personalized treatment approach, its development and regulation are facing numerous challenges. In this article, we briefly introduce the research progress and regulatory status of neoantigens in order to provide reference for the research and development and regulation of neoantigens in China.

Cellular therapy industry is booming in China. As increasing cellular therapy products are authorized and commercialized, hence higher requirements are set for the safety and efficacy of cellular therapy. As the essential starting raw material, the quality of donor materials directly affects the safety and quality of cell products, thus, the risk management of donor screening is crucial. Herein, the screening of infectious pathogens is a vital guarantee for the viral safety and biosafety of cellular therapeutics. Currently, no uniform standards or consensus have been reached for donor screening quality management system, thus the regulatory framework needs to be further supplemented. This paper discusses the current obstacles and challenges in donor screening, overall risk management strategies and technical considerations on infectious pathogen detection, and meanwhile reviews the relevant regulatory guidelines and requirements at home and abroad, aiming to provide reference for subsequent standardization and regulatory requirements for donor screening in cellular therapeutics.

Repeated SARS-CoV-2 infections still threaten public health around the world. Researchers are still committed to carrying out research on vaccines, small molecular antiviral drugs, and neutralizing antibodies to find more effective means of prevention and treatment for the infection of various mutants of novel coronavirus. Among them, neutralizing antibodies have the advantages of clear action mechanism, good safety, and convenience for large-scale production, so they are one of the therapeutic class of drugs with best potential to treat COVID-19. The research and development projects for SARS-CoV-2 neutralizing antibodies have been developing rapidly both at home and abroad. This paper briefly introduces the research status of SARS-CoV-2 neutralizing antibodies, focusing on providing special considerations for pharmaceutical evaluation of these class of drugs in combination with the practice of drug evaluation to promote the industrialization of the same class of domestic products as soon as possible.

Antibodies, as an important tool for treatment and prevention of viral infection, have been applied to the treatment and prophylaxis of viral infectious diseases. This article summarized the latest research progress in antibody products that target viruses, and discussed some quality assessment concerns in epitope mapping, neutralization spectrum evaluation, and quality control, expecting to promote the clinical transformation and application of such products.

Glucagon like peptide 1 (GLP-1) can inhibit the elevation of glucagon, inhibit gastric acid secretion, and slow down gastrointestinal peristalsis. However, the plasma half-life of GLP-1 is only a few minutes to a few hours. Frequent and high-dose administration are required to achieve therapeutic effects which will increase the risk of adverse effects. Therefore, long acting is an important research interest for GLP-1 drugs. Fatty acid chain modification is the widely used long-acting strategy for GLP-1 drugs due to its advantages of definite modification sites, low heterogeneity of modified products, low loss of biological activity, and low toxic effects. To provide references for the CMC research and evaluation of fatty acid chain-modified GLP-1 drugs and other fatty acid chain-modified peptide drugs, this article shares the experience accumulated in the evaluation of fatty acid chain-modified drugs and proposes the evaluation considerations for recombinant fatty acid chain-modified GLP-1 drugs from the perspectives of raw materials for production, production processes, quality control, and stability research.

Allergic diseases are recognized by the World Health Organization (WHO) as a major health problem in the world. At present, allergen products have been widely used in the treatment of various allergic diseases at home and abroad. Allergen therapy is currently the only therapy that can regulate the immune system in patients with allergic rhinitis. However, high quality allergen products are related to the effectiveness of the products. In view of the important clinical value of allergen products, combined with the status quo of listed allergen products and registered allergen products, this paper briefly introduces the registration management classification of allergen products in China and the United States and the technical requirements for the registration of such products in China.

Based on the requirement on the experimental data in the pharmaceutical patent examination of China National Intellectual Property Office (CNIPA), some recent administrative decisions of CNIPA, the repetition of experimental data in the development of some "blockbuster" drugs, and the relevant cases of the US Federal Circuit, this paper discusses the two sides of supplementary experimental data in pharmaceutical patent protection.

Hypophosphatasia (HPP) is a rare hereditary endocrine system disease characterized by bone and/or tooth mineralization disorders accompanied by decreased serum alkaline phosphatase activity. Asfotase alfa (AA) received orphan drug approval by FDA as a recombinant bone-targeted human nonspecific alkaline phosphatase and was marketed in 2015 for the treatment of HPP. This paper reviews the mechanism of action, pharmacokinetic characteristics, efficacy, safety, usage and dosage of AA to provide reference and evidence support for the use of AA in the patients with HPP.

There are many kinds of drugs for insomnia, but the current hypnotics on the market cannot fully meet the clinical needs. As a new treatment for insomnia disorder, dural orexin receptor antagonist (DORAs) has a different mechanism of action from the traditional hypnotics, it can avoid a series of common side effects of traditional hypnotics and has a good safety profile. A newly developed dual orexin receptor antagonist, daridorexant, has been studied in a number of clinical studies in global, and data shows that it improves both the sleeping disorder at night and daily functions, with good safety feature. This review comprehensively summarizes the efficacy, safety, and clinical data of the dual orexin antibody antagonist daridorexant in various clinical trials.

With China's accession to ICH and implementing a series of ICH guidelines, the pharmaceutical innovation system of China has been in line with international standards and deeply integrated into the global innovation system, making overseas declaration data can be used in China's new drug marketing application. The ability of global synchronous investigation and registration has been largely improved along with these development. Clinical trials gradually need to involve healthy foreign subjects, especially those who need to be compared in the pharmacokinetic characteristics of different races in order to bridge the existing data abroad. What are the similarities and differences between the management process of clinical research on healthy foreign subjects and their Chinese counterparts? What factors should be paid attention to? This article takes a phase I clinical trial involving Caucasian subjects as an example to share and discuss the implementation and management experience of clinical studies involving foreign subjects to answer these questions.