The burgeoning field of bioengineering has witnessed significant strides due to the advent of stem cell models, particularly in their application in advanced therapy medicinal products (ATMPs). In this review, we examine the multifaceted impact of these developments, emphasizing the potential of stem cell models to enhance the sophistication of ATMPs and to offer alternatives to animal testing. Stem cell-derived tissues are particularly promising because they can reshape the preclinical landscape by providing more physiologically relevant and ethically sound platforms for drug screening and disease modelling. We also discuss the critical challenges of reproducibility and accuracy in measurements to ensure the integrity and utility of stem cell models in research and application. Moreover, this review highlights the imperative of stem cell models to align with regulatory standards, ensuring using stem cells in ATMPs translates into safe and effective clinical therapies. With regulatory approval serving as a gateway to clinical adoption, the collaborative efforts between scientists and regulators are vital for the progression of stem cell applications from bench to bedside. We advocate for a balanced approach that nurtures innovation within the framework of rigorous validation and regulatory compliance, ensuring that stem cell-base solutions are maximized to promote public trust and patient health in ATMPs.

Advanced therapy medicinal products (ATMPs) are rapidly evolving to offer new treatment options. The scientific, technical, and clinical complexities subject drug regulatory authorizes to regulatory challenges. To advance the regulatory capacity for ATMPs, the National Medical Products Administration in China made changes to the drug regulatory system and developed regulatory science with the goal of addressing patient needs and encouraging innovation. This study aimed to systematically identify the regulatory evidence on ATMPs in China under the guidance of an overarching framework from the World Health Organization Global Benchmarking Tool. It was found that China's administrative authorities at all levels have issued a number of policy documents to promote the development of ATMPs, covering biopharmaceutical products research and development (n = 14), biopharmaceutical industry development (n = 9), high-quality development of medical institutions (n = 1), specific development plans/projects (n = 6) and specific regional development (n = 4). The legal and regulatory framework of ATMPs in China has been established and is subject to continuous adjustment in various aspects including regulations (n = 3), departmental rules or administrative normative documents (n = 22), and technical guidance (n = 15). As the regulatory reform continues, the drug review processes have been revised, and various technical standards have been launched, which aim to establish a regulatory approach that oversees the full life-cycle development of ATMPs in the country. The limited number of investigational new drug applications and approved ATMPs suggests a lag remains between the translation of advanced therapeutic technologies into clinically available medical products. To accelerate the translational research of ATMP in countries such as China, developing and adopting real-world evidence generated from clinical use in designated healthcare facilities to support scientific decision-making in ATMP regulation is warranted. The enhancement of regulatory capacity building and multi-stakeholder collaborations should also be encouraged to facilitate the timely evaluation of promising ATMPs to meet more patient needs.

Tissue-engineered products (TEPs) are at the forefront of developmental medicines, precisely where monoclonal antibodies and recombinant cytokines were 30 years ago. TEPs development for treating skin wounds has become a fast-growing field as it offers the potential to find novel therapeutic approaches for treating pathologies that currently have limited or no effective alternatives. This review aims to provide the reader with the process of translating an idea from the laboratory bench to clinical practice, specifically in the context of TEPs designing for skin wound healing. It encompasses historical perspectives, approved therapies, and offers a distinctive insight into the regulatory framework in Brazil. We explore the essential guidelines for quality testing, and nonclinical proof-of-concept considering the Brazilian Network of Experts in Advanced Therapies (RENETA) and International Standards and Guidelines (ICH e ISO). Adopting a multifaceted approach, our discussion incorporates scientific and industrial perspectives, addressing quality, biosafety, non-clinical viability, clinical trial and real-word data for pharmacovigilance demands. This comprehensive analysis presents a panoramic view of the development of skin TEPs, offering insights into the evolving landscape of this dynamic and promising field.

Advanced therapy medicinal products (ATMPs) have shown dramatic efficacy in addressing serious diseases over the past decade. With the acceleration and deepening of China's drug regulatory reforms, the country sees a continuous introduction of policies that encourage drug innovation. The capacity and efficiency of the Center for Drug Evaluation (CDE), National Medical Products Administration have significantly improved, where substantial resources have been allocated to ATMPs with major innovations and outstanding clinical values that satisfy urgent clinical needs. These changes have greatly stimulated the research and development of biological products in China, ushering in a period of explosive growth in the number of investigational new drug (IND) applications of ATMPs. Here, we described China's ATMP regulatory framework and analyzed data on IND applications for ATMPs submitted to CDE. The data show that China's ATMP industry is expanding dramatically, but lagging behind in terms of the innovative targets and the coverage of indications. However, in recent years, the diversity of product types, targets, and indications is growing. We discussed challenges and opportunities in ATMP regulation. Risk-based regulation and cross-discipline collaborations are encouraged to promote more ATMPs toward market authorization in China.

Solid tumors account for approximately 90% of all adult human cancers. As such, the development of novel cellular therapies has become of increasing importance to target solid tumor malignancies, such as prostate, lung, breast, bladder, colon, and liver cancers. One such cellular therapy relies on the use of chimeric antigen receptor T cells (CAR-T cells). CAR-T cells are engineered to target specific antigens on tumor cells. To date, there are six FDA-approved CAR-T cell therapies that have been utilized for hematologic B cell malignancies. Immune cell trafficking and immunosuppressive factors within the tumor microenvironment increase the relative difficulty in developing a robust CAR-T cell therapy against solid tumors. Therefore, it is critical to develop novel methodologies for high-throughput phenotypic and functional assays using 3D tumor spheroid models to assess CAR-T cell products against solid tumors. In this manuscript, we discuss the use of CAR-T cells targeted towards PSMA, an antigen that is found on prostate cancer tumor cells, the second most common cause of cancer deaths among men worldwide. We demonstrate the use of high-throughput, plate-based image cytometry to characterize CAR-T cell-mediated cytotoxic potency against 3D prostate tumor spheroids. We were able to kinetically evaluate the efficacy and therapeutic value of PSMA CAR-T cells by analyzing the cytotoxicity against prostate tumor spheroids. In addition, the CAR-T cells were fluorescently labeled to visually identify the location of the T cells as cytotoxicity occurs, which may provide more meaningful information for assessing the functionality of the CAR-T cells. The proposed image cytometry method can overcome limitations placed on traditional methodologies to effectively assess cell-mediated 3D tumor spheroid cytotoxicity and efficiently generate time- and dose-dependent results.

In the recent decade, chimeric antigen receptor (CAR)-T cell therapy has revolutionized strategies for cancer treatments due to its highly effective clinical efficacy and response for B cell malignancies. The success of CAR-T cell therapy has stimulated the increase in the research and development of various CAR constructs to target different tumor types. Therefore, a robust and efficient in vitro potency assay is needed to quickly identify potential CAR gene design from a library of construct candidates. Image cytometry methodologies have been utilized for various CAR-T cell-mediated cytotoxicity assay using different fluorescent labeling methods, mainly due to their ease-of-use, ability to capture cell images for verification, and higher throughput performance. In this work, we employed the Celigo Image Cytometer to evaluate and compare two CAR-T cell-mediated cytotoxicity assays using GFP-expressing or fluorescent dye-labeled myeloma and plasmacytoma cells. The GFP-based method demonstrated higher sensitivity in detecting CAR-T cell-mediated cytotoxicity when compared to the CMFDA/DAPI viability method. We have established the criteria and considerations for the selection of cytotoxicity assays that are fit-for-purpose to ensure the results produced are meaningful for the specific testing conditions.

Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. The uncertainty about the product's benefit-risk balance at the time of approval, the limitations of nonclinical development, and the complex quality aspects of those highly individualized advanced therapies are playing a key role in the clinical development, approval, and post-marketing setting for these therapies. This article reviews the current landscape of clinical development of advanced therapies, its challenges, and some of the efforts several stakeholders are conducting to move forward within this field. Progressive iteration of the science, methodologically sound clinical developments, establishing new standards for ATMPs development with the aim to ensure consistency in clinical development, and the reproducibility of knowledge is required, not only to increase the evidence generation for approval but to set principles to achieve translational success in this field.