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  Yoji Sato

  Head, Division of Drugs/Division of Cell-Based Therapeutic Products at National Institute of Health Sciences (NIHS)

The Center for Cell Manufacturing Technologies (CMaT) is an academic-industry-government partnership to advance the manufacturing of living cells for therapeutic applications. CMaT focuses on developing innovative new technologies to improve the safety and quality of therapeutic cells and to reduce the manufacturing cost, increasing accessibility to patients. I will discuss CMaT’s efforts to move cell manufacturing toward automated closed loop processes in three testbed cell types: engineered immune cells, mesenchymal stromal cells, and induced pluripotent stem cell-derived cells. I will present CMaT’s platforms using data analytic and machine learning models of imaging and -omics datasets to identify the critical quality attributes of these cell types, new sensors to monitor these CQAs, and technologies to scale and control the manufacturing processes.

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  Sean Palecek

  Professor, Department of Chemical & Biological Engineering at University of Wisconsin – Madison.

The Aseptic Product GMP Committee of PDA-Japan Chapter has been leading Japan in research and publication on Rapid Microbiological Methods (RMM) continuously and vigorously for about 13 years since 2010 to date. With the release of PIC/S GMP Annex 1 revision 1 in September 2022, this technology, which contributes to improving the quality of pharmaceutical products, is expected to attract even more attention and to expand its practical use globally. In light of the above, some of the research results of the committee, including case studies for the introduction of RMM, will be explained.

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  Mitsuo Mori

  Quality Control at Kyowa Kirin Co.,Ltd.

Welcome Remarks by the Moderators

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  Richard Denk

  Senior Consultant Aseptic Processing & Containment at Skan AG
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  Yasuhito Ikematsu

  Specially Appointed Associate Professor, Graduate School of Engineering at Osaka University

It is extremely difficult to establish sterility assurance by terminal sterilization for biological medical products such as cell-based health care products due to their product characteristics. Therefore, these products must be manufactured using aseptic processing, and an aseptic processing environment must be established and maintained to guarantee sterility in each process.
In particular, aseptic processing environments that require intervention by operators, such as biosafety cabinets, ensure sterility by identifying and controlling the risk of contamination posed by the activities of operators.

This study presents an example of a microbiological contamination risk assessment and associated strategic measures and controls under the condition of a specific cell processing process using a biosafety cabinet.

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  Tetsuya Karino

  Production Manager at Sumitomo Pharma Co.,Ltd.

The preparation for the commercial manufacturing for Cell & Gene should already start at the development stage of a new novel therapy. This keynote speech will focus on the Points to Consider for the Engineering of the commercial manufacturing of Cell & Gene. Considering equipment and room layout, GMP requirements, disposable technologies, modern technologies like robotics, cleaning and how to work with higher Biosafety Level 2 requirements.

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  Richard Denk

  Senior Consultant Aseptic Processing & Containment at Skan AG

In recent years, the development of cell and gene therapy products has accelerated, and several products are already in use in the medical field. While viral safety is an important quality item in the safety of these products, there are cases in which clearance processes are not effective in the manufacture of some products and need to be considered. ICH Q5A, the viral safety guideline for biopharmaceuticals, has been revised to reflect technological advances, and the draft revision was released in October 2022, with gene therapy products newly included in the Scope. In this presentation, the role of virus filtration in ensuring viral safety of cell and gene therapy products will be discussed with reference to the three basic principles of ICH Q5A, including the following study cases: (1) Application of virus filtration for contaminated virus clearance in the AAV manufacturing process for gene therapy products, and (2) Application of filtration treatment to raw materials used for product manufacturing further upstream as a risk mitigation strategy.

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  Tomoko Hongo-Hirasaki

  Lead Expert on Virus Filtration at Asahi Kasei Medical Co., Ltd.

Alofisel® Injection is a suspension of expanded allogeneic (donor-derived), adipose-derived mesenchymal stem cells (eASC) , which was approved in Japan in Sep 2021 as the first cellular & Gene Therapy product in Takeda Japan. It has been supplied to patients in Japan since 2022. Alofisel Injection is expected to contribute to the improvement of QOL of patients as a therapeutic product for perianal fistulas in Crohn's disease. I would like to introduce the facilities introduction and tech transfer and validation for this product into Japan, and process & quality design for newly introduced isolator.

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  Seitaro Mizukami

  Takeda Pharmaceuticals Company Limited

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  Masahiro Kino-oka

  Professor, BioProcess Systems Engineering Lab., Dept.Biotech., Grad. Sch. Eng. at Osaka University
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  Tomoko Hongo-Hirasaki

  Lead Expert on Virus Filtration at Asahi Kasei Medical Co., Ltd.
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  Masayoshi Tsukahara

  Center for iPS Cell Research and Application at Kyoto University
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  Seitaro Mizukami

  Takeda Pharmaceuticals Company Limited
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  Sang Yoon

  Senior Director of Quality at Samsung Biologics

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  Shingou Sakurai

  Professor of Facility, Pharmaceutical Sciences at Tokyo University of Science

Akiyoshi Kunieda
Office of Cellular and Tissue-based Products at PMDA

In reviewing the quality of regenerative medicine products for approval, it is necessary to confirm that manufacturers can continuously manufacture products with a certain level of quality. For this reason, management of raw materials and quality control are important points.

In this presentation, I will first classify regenerative medicine products into several categories according to their characteristics, show specific examples of inquiries in each review, and outline the items that are particularly controversial.

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  Shingou Sakurai

  Professor of Facility, Pharmaceutical Sciences at Tokyo University of Science

When a manufacturing process is changed without compromising the efficacy and safety of a cell therapy product during a clinical trial or at a later development stage, the comparability of the product quality between before and after the change must be demonstrated. The evaluation of comparability requires critical quality attributes (CQAs) of the product and specifications/test methods based on the CQAs.
However, compared to conventional pharmaceutical products, the cell populations that comprise cell therapy products are extremely complex, dynamic, and not necessarily homogeneous, making it extremely difficult to comprehensively identify all CQAs. In addition, not all cells in a cell therapy product may equally retain efficacy-related physiological functions, and it is possible that only a small subset of the cells may elicit efficacy. Therefore, for flexible change/improvement of the manufacturing processes of cell therapy products, it is useful to develop tools for identifying of CQAs or uncovering a cell subpopulation that is a true active ingredient.
In my talk, I will introduce a new approach we have recently developed for CQA identification, using human mesenchymal stem/stromal cells as an example, in which single cell transcriptome analysis is applied for "mining" a cell subset responsible for a specific cell function.

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  Yoji Sato

  Head, Division of Drugs/Division of Cell-Based Therapeutic Products at National Institute of Health Sciences (NIHS)

Regenerative medicine and cell therapy use the cell transplants which are manufactured, requiring interdisciplinary activities not only from medicinal and biological fields but also from manufacturing field. In cell production for regenerative medicine and cell therapy, process development is essential to improve the efficiency and stability of cell product quality. Unlike conventional pharmaceutical manufacturing,
The quality of cell products tends to be unstable due to the inherent characteristics of cells, which is an obstacle to mechanization and scale-up of manufacturing. Therefore, it is essential to develop a unique concept.
We proposed the discipline for cell production, which is ‘cell manufacturability’ to be defined as capability of cell manufacturing through the processes by bridging between biological and process aspects. And ‘Design for cell manufacturability’ is to be manufacturing design of cell-based products in such a way that they are easy to manufacture through simple, safe and efficient (cost-saving) process with stable product quality and secure to customer by considering transportation and preparation outside factory, acting practically the system optimization for the efficiency and stability of the process by understanding the requirement gap between biological and engineering aspects and reducing output fluctuation. This action will lead to stable process and cost saving of the products through the process simplification and governing the kinetics of cell behavior.

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  Masahiro Kino-oka

  Professor, BioProcess Systems Engineering Lab., Dept.Biotech., Grad. Sch. Eng. at Osaka University