Objective：To clarify the significance of stability studies and elaborate on the special considerations and current challenges in the stability studies for biological products. Methods：According to the characteristics of biological products, the scientific basis for the low stability and easy degradability of such products was elucidated. By reviewing different regulatory guidelines relating to stability studies, we identified the significance of different stability studies for the life-cycle management of biological products. In addition, we summarized the contents of stability studies required at various stages throughout the life-cycle management, and put forward some special considerations for biological product stability studies. Finally, in response to the challenges currently encountered in the development of biological products, we proposed some suggestions. Results and Conclusion：Stability studies are of great significance to the life-cycle management of biological products. Scientifically and rationally designed stability studies can accelerate the product development process and improve the overall efficiency of life-cycle management.

Human papillomavirus (HPV) infection imposes a substantial disease burden, with more than one million new cases of HPV-related cancer and hundreds of thousands of related deaths worldwide each year. HPV vaccines are the most economical and effective means of preventing and controlling diseases caused by HPV infection. Since the approval of the world’s first HPV vaccine in 2006, significant progress has been made in HPV vaccine research and development (R&D) both in China and abroad. This article reviews the current status of HPV vaccine marketing approval and R&D and, in conjunction with the technical guidelines for vaccine clinical trials issued in China and relevant regulatory requirements, systematically discusses key considerations in clinical research and development of HPV vaccines, including indications and primary clinical trial endpoints, target vaccination populations and study populations, HPV type coverage and iterative development strategies, and safety evaluation. The aim is to provide a reference for vaccine developers and relevant researchers in formulating clinical research and development strategies. Currently, HPV vaccine R&D in China is gradually shifting toward the development of higher-valency vaccines. The proposal of iterative strategies may significantly accelerate the clinical research and development of higher-valency HPV vaccines. However, vaccine developers should fully assess and recognize the challenges associated with the similarity of the material basis when adopting such strategies, as well as those related to clinical trial implementation and management.

Human Stem cell-derived extracellular vesicles (EVs), as derivatives of stem cells, possess multiple advantages, including low immunogenicity and high tissue compatibility, and have shown broad application prospects in tissue repair, immunomodulation, and neural regeneration. However, owing to their inherent heterogeneity, compositional complexity, and high sensitivity to manufacturing processes, the pharmaceutical research of EVs faces numerous challenges, and their clinical translation remains bottlenecked. Based on the biological characteristics of EVs and current research knowledge, this article summarizes the key issues that require attention in the pharmaceutical research of human stem cell-derived EV therapeutics, including production cells, cell culture and purification processes, formulation development, quality research, and stability studies, with the aim of providing a reference for the research and development of related products. Developers should, based on product characteristics and risks, continuously accumulate sufficient pharmaceutical research data and gradually establish and improve a scientific pharmaceutical research and evaluation system, thereby laying a foundation for the translation of EV therapeutics from the laboratory to the clinic.

Objective：To provide insights into the application prospects of artificial intelligence (AI)-assisted tools in the research and development (R&D), manufacturing, and regulatory process of biosimilars. Methods：The application progress of AI-assisted tools by major global pharmaceutical regulatory authorities and in the R&D and manufacturing of biosimilars was reviewed. The application prospects of AI-assisted tools in the Chemistry, Manufacturing, and Controls (CMC) research and evaluation of biosimilars were analyzed. Anticipated applications and potential practical examples were further proposed for analytic similarity assessment and exemption of comparative efficacy study, and the actual challenges faced by the implementation of such tools in practice were summarized and discussed. Results and Conclusion：Massive datasets generated throughout the R&D and manufacturing process of biosimilars fit well with the application scenarios of AI-assisted tools. These tools can integrate multi-dimensional quality analysis datasets, quantitatively resolve molecular modification characteristics, and construct standard quality characterization profiles, thereby advancing digital and precise control over similarity evaluation. Despite numerous challenges remaining for AI-assisted regulatory review, including training dataset screening, software-hardware confidentiality management and control, and result bias correction, such tools possess broad application potential. They can lay a foundation for building up China’s strength in pharmaceutical manufacturing and producing greater benefits for patients.

Objective：To guide the blood product manufacturers in the research and development of human fibrinogen products, thus providing a reference for process optimization and quality improvement of human fibrinogen in China from a technical perspective. Methods：On the basis of previous technical review cases in China, pharmaceutical literature on human fibrinogen, and technical guidelines for blood products, this article summarizes the research requirements and reporting materials for human fibrinogen from a pharmaceutical evaluation perspective. Results and Conclusion：This article systematically summarizes product features of human fibrinogen, the overview of marketed products, viral safety control strategies, key quality control considerations, and the current status of manufacturing processes. In light of common issues encountered in the technical evaluation of human fibrinogen, it further highlights key aspects warranting attention in the regulatory review. These findings are expected to clarify the current research status and key issues in pharmaceutical studies of human fibrinogen in China.

Objective：To review the research and development progress of drugs for Duchenne muscular dystrophy (DMD), analyze the key issues in the nonclinical evaluation of various drugs from a pharmacological and toxicological perspective, and provide references for the nonclinical research and evaluation of DMD drugs in China. Methods：Publicly available review documents and references for approved DMD drugs worldwide were systematically reviewed. The nonclinical study designs, major findings, and regulatory considerations of drugs developed through different technical approaches were summarized. Results and Conclusion：The development of DMD drugs has gradually shifted from hormone-based supportive therapy to targeted interventions at the genetic level. Various novel therapies face unique challenges in nonclinical studies. In the context of rare diseases, regulatory agencies allow appropriate simplification of studies; however, this should be based on adequate risk control. During drug development, attention should be paid to the selection of animal models and species, comprehensive characterization of target organ toxicity, design of juvenile animal studies, and validation of the correlation between animal endpoints and clinical benefits.

Objective：Cell therapy medicinal products (CTMPs) represent one of the strategic sectors within the biopharmaceutical industry, which is an emerging pillar industry in China. To standardize the scope and classification of CTMPs in China, based on a survey of international regulatory classification frameworks, combined with considerations of the development stage of relevant industry sectors, regulatory practices, and the formulation of technical guidelines in China, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) organized and officially issued the Technical Guideline for Scope and Classification of Cell Therapy Medicinal Products (2026 Edition) (hereinafter referred to as “the Guideline”). This article provided an in-depth analysis and interpretation of the Guideline, with the aim of providing references for the industry and regulatory authorities. Methods：By examining the drafting ideas, revision process, and main content of the Guideline, as well as a comparative analysis of international regulatory classification approaches, this article systematically elucidated the core connotations and extensions of the Guideline. Results：The Guideline established, for the first time, the scope and boundaries of CTMPs under the drug regulatory framework in China. Based on three key elements—material basis and active ingredients, manufacturing processes, and mechanisms of action, a two-tier classification framework for CTMPs was established, and the scientific principles and logic approaches for category determination were clarified. This article further explored the vital significance and impact of the Guideline in facilitating scientific classification guidance, improving the drug regulatory science system, standardizing and guiding research and development and regulatory submission, introducing supportive policies to accelerate review and approval for market access, and promoting alignment with international standards. Conclusion：The Guideline addresses current needs while reserving room for innovation to accommodate new products and emerging business formats. In the future, through a dynamic adjustment mechanism, the scientific classification system will be continuously refined to better suit China’s national conditions, thereby empowering the high-quality development of CTMPs industries.

Objective：To ensure the robustness and controllability of production processes as well as the stability and consistency of product quality, thus providing references and insights for the standardized and normalized development of the chimeric antigen receptor T-cell (CAR-T) therapy industry. Methods：Considering the technological features and inherent properties of CAR-T products, this article systematically discussed the key points of process validation from the dimensions of critical material control, whole production process control, quality testing methods, production equipment management, and production capacity expansion validation. Furthermore, this article summarized the key considerations in the validation of cell therapy products throughout the whole process encompassing product development, technology transfer, and commercial-scale production. Results：Donor material variability is a primary factor affecting CAR-T product quality, which can be mitigated through rational process design. For process performance qualification, tolerance interval analysis based on historical batch data is feasible for establishing acceptance criteria. In continued process verification, statistical process control tools are effective in detecting process drifts. For production capacity expansion, multi-batch parallel manufacturing poses a risk of overlapping harvests, necessitating worst-case validation to confirm system capacity. Additionally, given the “black-box” effect and amplified failure consequences associated with cell therapy integrated systems, failure mode simulation serves as a reliable approach to verify the accuracy of risk assessments. Conclusion：The systematic implementation of the three lifecycle stages—process design, process performance qualification, and continued process verification—establishes a comprehensive process validation framework that effectively ensures process robustness and batch-to-batch consistency in CAR-T product quality.

In recent years, the gene therapy medicinal products industry has demonstrated robust growth momentum, providing new therapeutic options for circulatory system diseases, ophthalmic diseases, and other conditions. These products exert their effects by specifically modifying human gene sequences or regulating gene expression. Characterized by complex and diverse active ingredients, marked quality heterogeneity, and rapidly advancing technology, gene therapy medicinal products call for a framework defining product scope and regulatory classification, which constitutes an essential foundation for the scientific regulation of such products. To systematically propose a scope-defining framework and classification operational guidelines for gene therapy medicinal products in China, and to provide reference for both developers and regulatory agencies on product classification, as well as to standardize industry practices in R&D and marketing authorization applications, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) officially issued the Technical Guideline for the Scope and Classification of Gene Therapy Medicinal Products (2026 Edition) (hereinafter referred to as “the Guideline”) in July 2026. This article aims to provide an interpretation of the Guideline by covering the current status of research, development, and regulatory review of gene therapy medicinal products in China, the scope and classification requirements for such products by major international regulatory authorities, the process of drafting and revising the Guideline, its main content, and explanations of key issues. It also analyzes the impact of the Guideline on the technical review system for gene therapy medicinal products and its role in promoting industrial development, for the reference of readers. As various types of gene therapy medicinal products continue to evolve and mature, the relevant technical considerations will be dynamically updated accordingly.

Objective：In recent years, the research and development of recombinant adeno-associated virus (rAAV) vector-based gene therapy products has kept advancing, with multiple products approved for marketing worldwide. However, rAAV products are characterized by complex manufacturing processes and high quality heterogeneity, and the relationships of critical quality attributes with the safety and efficacy of such products are still being elucidated through ongoing research. International regulatory experience shows that safety issues with rAAV products persist, and their quality control and marketing authorization review face considerable challenges, necessitating targeted addressing strategies. Methods：This article, on the basis of relevant technical guidance documents previously issued by the Center for Drug Evaluation and the marketing authorization review practices for such products, provides a technical review focusing on the process, quality research, and control considerations of rAAV products at the stage of marketing authorization application. Results：The process study data for rAAV products at the marketing stage are expected to demonstrate that the established process possesses satisfactory robustness and reproducibility, and can guarantee the continuous production of uniform quality products; the characterization results are intended to support the safety and quality controllability of the products. Conclusion：At the stage of rAAV product marketing authorization application, it is necessary, on the basis of a full understanding of the product’s critical quality attributes, to comprehensively carry out pharmaceutical research and establish a scientifically sound quality management system, thus providing assurances for the safety, efficacy, and consistent product quality.

Objective：To address the limitations such as long manufacturing cycle and limited accessibility of autologous chimeric antigen receptor T-cell (CAR-T) therapy and to sort out the technical pathway of in vivo CAR-T mediated by engineered viral vectors, thus providing reference for its molecular design and pharmaceutical research. Methods：Focusing on lentiviral and adeno-associated viral vectors, this paper summarized the molecular optimization strategies of vectors and analyzed the key points of pharmaceutical quality control according to relevant guidelines. Results：Engineered lentiviral vectors are the mainstream solution for clinical translation of in vivo CAR-T. Specific in situ transduction of T cells can be achieved through envelope modification and targeted ligand integration. Pharmaceutical research requires a matched targeted activity evaluation system and targeted safety detection methods. Conclusion：In vivo CAR-T mediated by engineered viruses has the potential to overcome the limitations of conventional therapies. Targeted molecular optimization and systematic quality control are the key guarantees for the clinical translation of in vivo CAR-T.

Objective：To systematically review the research advances and the general profile of technical review for antibody-oligonucleotide conjugates (AOC) in major countries, regions, and international organizations, while offering considerations on the chemistry, manufacturing and controls (CMC) technical requirements for AOC development to facilitate communications between industry and regulatory authorities. Methods：A comprehensive literature review was conducted to summarize the global research and development progress in AOC. On the basis of accumulated experience in regulatory review and a comparative analysis of the shared characteristics and unique features between AOC and antibody-drug conjugates (ADC), the study summarized the general profile of technical review and propose several considerations for CMC technical requirements for AOC products. Results and Conclusion：AOC possesses pharmaceutical characteristics of both chemical drugs and biologics. The technical review therefore requires comprehensive evaluation of the quality attributes for oligonucleotides, antibody intermediates, and AOC. Major regulatory authorities, including those in China, the United States, the European Union, Japan, as well as WHO, have issued a series of relevant technical guidelines. However, there is still a lack of product-specific technical guidelines for AOC. This paper proposes considerations for CMC technical requirements for AOC in four key areas: structural complexity and pharmaceutical research, mechanism diversity and efficacy bottlenecks, manufacturing process characteristics, and quality control. A systematic review of the research advances, general profile of technical review, and CMC technical requirements for AOC provides a valuable reference for both industry and regulatory authorities in the research and evaluation of such products, thereby effectively supporting the high-quality and rapid advancement of innovative drugs.

Objective：To propose targeted pharmaceutical review considerations based on current research, development, and application status of recombinase products and tool enzymes in China, combined with regulatory review practice, aiming to provide a reference for the research, development, and regulatory submission of such products. Methods：The domestic and international registration status of therapeutic recombinase biological products was systematically reviewed. The products were classified into two major categories: recombinase products and tool enzymes, followed by a classified analysis based on pharmaceutical review experience, relevant literature, and common issues. Results and Conclusion：Compared with conventional recombinant protein products, recombinase products are distinctive in molecular properties, quality studies, and stability. Therefore, it is essential to establish an “activity-centered” quality concept. Rather than focusing solely on protein structural integrity, biological activity maintenance should be the primary objective in molecular design, process development, quality studies, and stability evaluation. Moreover, given that tool enzymes play a critical role in drug manufacturing processes, they should be regarded as key raw materials and managed in accordance with corresponding regulatory requirements. The same technical standards should apply, whether tool enzymes are self-made or externally sourced.