The guidance on CMC study of in vivo gene therapy products was issued by the Center for Drug Evaluation, NMPA, on May 26, 2022, to encourage and promote the development of in vivo gene therapy products. This paper gives a detailed interpretation of the main contents and some important issues of the guidance and provides a reference for the market authorization application, combined with the drafting process of the guidance, so that the industry can better understand the technical requirements of the guidance during the development of in vivo gene therapy products.

A large number of investigational new drug (IND) applications of cellular products have been submitted in recent years. Up to October 2022, two cellular products have been approved to be marketed in China, which provide effective therapeutic approach to treat serious diseases. Genetic manipulation systems are used to modify or edit genes in various types of cellular products, including lentivirus, γ-retrovirus, adenovirus, sendaivirus or other viral vectors, as well as DNA, RNA, protein, protein-RNA complex or other non-viral vector systems. A guidance on CMC study and evaluation of ex vivo genetic manipulation systems was issued by CDE, NMPA on May 2022, in order to illustrate criterions on CMC research and evaluation of such systems. This paper provides a detailed interpretation of the guidance, combined with the guidance drafting logic, to help readers better understand the content of the guidance.

A guidance on CMC study and evaluation of immune cell therapy products was issued by CDE, NMPA on May 2022 in order to illustrate criteria on CMC research and evaluation of such products. This paper provides a detailed interpretation of the guidance, combined with the guidance drafting background and characteristics of immune cell therapy products, to help readers better understand the content of the guidance.

"Risk Assessment and Mitigation Strategies" (REMS) are procedures used by the U.S. Food and Drug Administration (FDA) to manage known or potentially serious risks associated with a drug to ensure that the benefits of the drug outweigh its risks. CAR-T cell therapy has brought new hope and new options for cancer patients due to its excellent efficacy. However, due to the characteristics of its treatment principle, almost all CAR-T cell therapy may lead to some adverse reactions. Cytokine release syndrome (CRS) and neurologic toxicities (NT) are the most common. This paper intends to analyze the post-marketing risk management strategies of CAR-T drugs in the United States by exploring the content of REMS in the risk management strategies of CAR-T drugs, and takes Kymriah, a CAR-T product currently on the market in the United States, as an example to analyze the specific implementation of the strategies. The purpose of this paper is to provide reference for the authorities to develop related policies of CAR-T drug listing risk management in China.

Continuous manufacturing is one of the development directions of the production process of recombinant biotechnology products in the future. The promulgation of important technical documents such as ICH Q13 also provides guidance for its application practice. However, in the field of viral safety control, there are great differences in control concepts and measures between continuous manufacturing and previous batch manufacturing mode. Starting with the process characteristics of continuous manufacturing, this paper makes a preliminary discussion on three aspects, which are the control of raw materials, in-process test, and virus removal/inactivation process validation. At the same time, as the cases of continuous manufacturing of recombinant biotechnology products are still limited, more comprehensive and meticulous control strategies and measures still need further accumulated and improved based on R&D and production experience. It is suggested that the applicants of this kind of products should fully communicate with the regulatory authorities before the application, so as to ensure the safety of the subjects or patients through scientific and rigorous trial design.

As a continuous cell culture technology, perfusion fermentation is more beneficial to cost control than traditional batch fermentation and can be flexibly arranged according to the supply change. In this paper, the characteristics and advantages of perfusion fermentation are clarified by comparing the batch fermentation with perfusion fermentation. In combination with the guidelines currently being drafted by the International Council on Harmonization, the considerations for pharmaceutical evaluation of cell passage stability study, batch and scale definition, process control, viral safety, and process verification of perfusion fermentation are summarized in this paper.

Antibody radionuclide conjugates (ARC) conjugate radionuclides and antibodies through a linker and chelator, which can perform different functions of diagnosis or treatment. To date, ARC is an important product type of radionuclide drug conjugates (RDC), and there are many approved drugs and drug candidates in clinical trials. However, the domestic industry faces many challenges in the development of clinical application-grade ARC products. This article summarizes the latest research progress of ARC products, from raw materials, production process and quality control, expecting to promote the clinical transformation and application of such products.

Stem cells have the potential of self-renewing and multilineage differentiation. Different types of stem cells have different advantages and limitations. It has become a hot topic of basic research and clinical application. Currently human-derived stem cell products to be developed as drugs come mainly from adult stem cells, embryonic stem cells, and induced pluripotent stem cells. Human-derived stem cell products are complex and diverse, showing unique therapeutic advantages in the treatment of a variety of diseases. This paper summarizes the characteristics and the latest research progress of human-derived stem cell products. According to the drug development and evaluation rules, this article brings up some quality assessment concerns and discussions in the major fields, such as raw materials, manufacturing process, quality research and control, stability, packaging container system, for the industry and regulators to discuss and communicate, expecting to promote the clinical transformation and application of this class of products.

Single-cell sequencing advances the research of molecular biology and cell biology to the single cell level by integrating the latest technologies such as single-cell dissociation, microfluidic, microfluidics system, high-throughput sequencing, and bioinformatics. It is a milestone technology in the history of biotechnology. Single-cell sequencing technology provides a new dimension for the study of basic biomedical problems such as ontogeny, cell differentiation, cell heterogeneity in tissues, and the etiology and development of diseases, and has been widely used. In this review, we briefly introduced the development of single cell sequencing technology and assocatied bioinformatics methods, and reviewed its application in the process of drug development, such as study on mechanism of disease, target discovery, drug discovery and optimization, mechanism of action and clinical trial design.