Autoimmune diseases remain a major cause of chronic morbidity despite substantial advances in targeted immunomodulatory therapies. In many autoantibody-mediated conditions, disease refractoriness and relapse are driven by long-lived plasma cells, which are largely resistant to conventional immunosuppression and upstream B cell-directed strategies. CD38, a surface molecule highly expressed on plasmablasts and plasma cells and functionally involved in immunometabolic regulation, has emerged as a promising therapeutic target to overcome this limitation. Clinical interest in anti-CD38 therapy has been catalyzed by experience in plasma cell dyscrasias, where anti-CD38 monoclonal antibodies induce rapid and profound depletion of antibody-secreting cells. Over recent years, accumulating reports and early-phase studies have explored the repurposing of CD38-directed therapies in severe, treatment-refractory autoimmune diseases. The most compelling evidence has emerged in lupus nephritis and immune thrombocytopenia, with additional proof-of-concept data in autoimmune cytopenias and plasma cell-driven renal disorders such as immunoglobulin light chain (AL) amyloidosis. These experiences suggest that targeting CD38 can lead to meaningful clinical and immunological improvement, often accompanied by rapid reductions in pathogenic autoantibody production. However, the current evidence base remains heterogeneous and largely derived from small cohorts, case series, and early-phase trials, and important questions remain regarding durability of response, optimal treatment strategies, and long-term safety, particularly with respect to hypogammaglobulinemia and infection risk. We summarize the biological rationale for CD38 targeting in autoimmunity and plasma cell-driven immune-mediated diseases, critically appraise the emerging clinical evidence across disease settings, and discuss key challenges and future directions for integrating plasma cell-directed therapies into immunological disease management.

Advanced therapy medicinal products (ATMPs) promise transformative clinical potential, but their use remains limited by complex manufacturing, high prices, and fragmented market access. To explore the existing and potential regulatory pathways to increase access to ATMPs, we conducted a product-level analysis of ATMPs and biologic medicines submitted to the European Medicines Agency up to May 2026, and a review of regulatory pathways and policy frameworks. While certain scientific principles from biologic and biosimilar regulation, such as totality of evidence, fit-for-purpose data, and tailored approaches are transferable, the biosimilar pathway may not be suitable for certain ATMPs. Other approaches, including bio-hybrid applications or prior knowledge-based dossiers, may be better suited to support competitive entry and second-wave innovation. Tailored follow-on pathways, open and well governed platform technologies, and supportive industrial and data sharing policies, are key to facilitate the translation of the scientific promise of ATMPs into sustainable and equitable patient access.

Maintaining quality consistently after any manufacturing change is essential for all biologic medicines and is ensured through well-established scientific and regulatory principles. Over nearly 30 years, such manufacturing changes post-approval have been successfully managed and regulated with so-called comparability approaches, and these have become standard regulatory practice globally as ICH Q5E. A robust comparability assessment along with current good manufacturing practices (cGMP)-based regulatory control, maintains consistent product quality over the full lifetime of a product. The occurrence of 'quality drift' (also mislabelled as divergence) reflecting poor manufacturing control has been observed in some rare originator cases but not for biosimilars, nonetheless, highlighting the need for meticulous control. Despite this, hypothetical concerns regarding 'drift' between the originator product and biosimilar products continue to surface and are often portrayed as a unique risk created by biosimilars. This raises an important question: why are biosimilars associated with concerns about drift? Such concerns are unsupported by real-world evidence. Numerous biosimilar products have been maintaining consistent quality over extended periods, in some cases over a decade of use, thereby strengthening confidence in comparability methods and cGMP-based regulatory control. Such confidence then supports approved biosimilars, including interchangeable products, by showing that serial comparability assessments can occur independently for any given biologic. Consistent application of regulatory science to all biologics further demonstrates that good manufacturing control is independent of any specific regulatory pathway or business model.

Uveal melanoma is the most common primary intraocular malignancy in adults and remains associated with poor outcomes once metastatic disease develops. Despite advances in local tumour control and molecular prognostication, effective systemic therapies capable of delivering durable benefit are limited. A range of gene-based therapeutic strategies have been explored in uveal melanoma, including immune-based approaches, gene-modified cell therapies and direct gene delivery. While these strategies have yielded important biological insights and modest clinical advances, their broader impact has been constrained by challenges related to delivery, tumour specificity, durability of effect and translational feasibility. This review surveys the current landscape of gene-based therapies investigated in uveal melanoma and synthesises lessons learned from these approaches, with a particular emphasis on the delivery platform as a determinant of therapeutic success. We examine the emerging potential of adeno-associated virus vectors as gene-delivery platforms for uveal melanoma, drawing on their safety profile and capacity for sustained transgene expression. We highlight the need for adaptation beyond native adeno-associated virus serotypes and discuss advances in capsid engineering, targeting strategies and control mechanisms that enable tumour-selective gene delivery. Finally, we consider translational challenges and future directions for integrating targeted adeno-associated virus-based approaches into therapeutic strategies for uveal melanoma.

Monoclonal antibodies (mAbs) have revolutionized therapeutic treatments by their ability to target specific antigens, leading to enhanced clinical outcomes over other drugs. They are one of the largest modalities within the growing biotherapeutics space and are indicated for a range of diseases. Though transformative, mAbs are still not readily accessible to many patients globally because of their high costs. An increasing number of mAbs are losing patent exclusivity, which has opened the door for the development of biosimilars that could drive down costs and ensure increased access to these life-saving drugs. Regulators approve biosimilars after conducting a rigorous evaluation similar to any other biologic medicine to ensure the safety, quality, and efficacy of these products. To establish biosimilarity, extensive comparative analytical and clinical studies of the biosimilar product with the approved reference product is a regulatory expectation. Growing acceptance from regulators to potentially waive clinical efficacy studies when robust evidence for similarity with reference product is established from analytical, functional, and pharmacokinetic/pharmacodynamic studies will have a major impact on reducing the time and cost of developing biosimilars. Comparative analytical assessment includes side-by-side analysis of the biosimilar with the reference product to demonstrate similarity regarding their physicochemical and functional characteristics. This is usually achieved by identifying product quality attributes (PQAs) that could impact clinical safety and efficacy and applying orthogonal analytical methods to characterize these attributes to identify any differences between the products. This review identifies the common PQAs studied for approved mAb biosimilars in the United States and the European Union through to the end of 2024. We have also compiled the data for the analytical methods used to characterize these attributes and identified a subset of methods universally used among biosimilar applicants. Finally, a brief overview of the risk-based analysis of attributes is summarized from the regulatory submissions.

Biosimilars are a critical strategy for improving access to high-cost biologics and ensuring the sustainability of healthcare systems worldwide. Over the past decade, China has transformed from a nascent market into one of the world's most active regions for biosimilar development. This review evaluates this transformation with a focus on regulatory evolution, approval dynamics, and global integration. We trace the development of China's biosimilar regulatory framework from the foundational 2015 Technical Guidelines to the current system of 19 technical and product-specific guidelines, highlighting the maturation of a stepwise, science-driven comparability paradigm aligned with international regulatory standards. Drawing on a systematic analysis of 83 biosimilars approved between 2019 and 2025, we analyze trends across molecular classes, therapeutic areas, and regulatory review pathways, illustrating how regulatory expectations and sponsor development strategies have evolved through representative case examples. Notably, the 2025 annual reports from both the US Food and Drug Administration and European Medicines Agency emphasize the increasing number of biosimilar approvals, therefore, we place China's approval experience in brief comparative context. Finally, we discuss China's expanding biosimilar development pipeline in the context of the forthcoming global biologics patent cliff and ongoing international initiatives to streamline biosimilar development, highlighting China's increasing integration into the global biopharmaceutical landscape.

The ever-increasing trend of antibiotic resistance necessitates new therapeutic strategies for fighting infection. Standing on decades of extensive research and development, monoclonal antibodies have great promise for treating antibiotic-resistant bacterial infections. In this comprehensive review of the field, we summarize the rapidly emerging field of monoclonal therapeutics that offer alternative approaches to target bacterial pathogens that pose critical concern to human health. Organizing the findings by species and by molecular target, we discuss antibodies that have demonstrated therapeutic potential as well as those that did not provide efficacy, highlighting new insights for the design and discovery of highly effective therapeutics for the future. Furthermore, we discuss the latest advances in molecular biology that have revolutionized the implementation, efficacy, and utility of monoclonal antibodies as therapeutics, and that continues to drive what will be an exciting era for antibacterial monoclonal antibodies.

Seasonal influenza epidemics and pandemics remain a persistent public health threat. A universal influenza vaccine is urgently needed. Such a vaccine must accommodate rapid viral evolution, strain diversity-including types A and B and their many subtypes-and the complexities of human immune history and biases. Messenger RNA (mRNA)-formulated lipid-nanoparticles have evolved from an emergency pandemic vaccine experiment into a versatile vaccine platform. This technology has demonstrated potential to address several critical challenges in developing a universal influenza vaccine, including rapid strain updates, the production of high-valent formulations, and the ability to target conserved antigens that may induce broader and longer-lasting protection. This review summarizes recent studies and applications of multivalent antigen selection strategies and self-amplifying and circular RNA vaccine platforms to develop mRNA influenza vaccines to achieve vaccine universality, with an emphasis on immune responses against conserved targets. We also review the latest advances in generating long-term mucosal immunity against influenza through optimized mRNA delivery. Finally, we discuss practical considerations for correlates of protection, manufacturing, and accessibility, pioneering mRNA vaccine candidates heading to clinical trials, and milestones that define vaccine "universality."

Antimicrobial resistance poses a critical and escalating threat to global public health, driven by the widespread and often unjustified use of antibiotics and the rapid dissemination of resistance determinants. With the antibiotic discovery pipeline largely depleted, alternative and complementary strategies are urgently needed to preserve the effectiveness of existing antimicrobials. Bacteriophages-viruses that specifically infect bacteria-have re-emerged as promising tools not only for direct bacterial eradication but also for reshaping bacterial evolutionary trajectories. This review examines the concept of phage-driven restoration of antibiotic susceptibility, focusing on evolutionary trade-offs that arise when bacteria adapt to phage pressure. Resistance to bacteriophages frequently involves modifications of surface structures, capsules, or efflux systems, changes that often incur fitness costs manifested as reduced virulence, impaired biofilm formation, or increased antibiotic sensitivity. Experimental studies and clinical case reports demonstrate that phage-antibiotic synergy can suppress bacterial growth more effectively than monotherapy, limit resistance emergence, and resensitize multidrug-resistant pathogens to previously ineffective antibiotics. Particular attention is given to mechanisms involving efflux pump targeting, capsule loss, biofilm disruption, and temperate phage-antibiotic interactions. In addition, emerging strategies that combine bacteriophages with CRISPR-Cas systems enable precise targeting and removal of resistance genes, offering a highly selective means to restore antibiotic efficacy and curb horizontal gene transfer. Together, these findings highlight bacteriophages as powerful evolutionary and therapeutic tools capable of giving antibiotics a "second chance". Integrating phage-based approaches into antibiotic stewardship frameworks may represent a sustainable path forward in combating multidrug-resistant bacterial infections.