Topics CMC Strategy Forum Japan 2022" held

Printable PDF

CMC*1 Strategy Forum Japan 2022" was held by CASSS (California Separation Science Society) on December 5-6, 2022. The conference was held online, as it will be in 2020 and 2021, because the new coronavirus infection (COVID-19) has not yet been contained.

Background of CMC Strategy Forum Japan

The CMC Strategy Forum was spun off from the Well Characterized Biotechnology Pharmaceutical (WCBP) Symposium in 2002, and after the first meeting in the U.S., the Forum has been held in Europe since 2007, Japan since 2012, Latin America since 2014, and the U.S. since 2021. The CMC Strategy Forum is a forum where experts from industry, academia, and regulatory agencies spend ample time discussing issues related to the research and development, manufacturing, and regulation of biopharmaceutical CMCs, in order to promote mutual understanding and problem-solving. The CMC Strategy Forum in Japan is a forum for companies, academia, and regulators to discuss issues related to biopharmaceutical CMC R&D, manufacturing, and regulation.

The PMDA and the Pharmaceutical Manufacturers Association of Japan (PMAJ) formed a preparatory committee for the CMC Strategy Forum in Japan, which has spent about a year in preparation, not only for selecting themes and deciding the direction of discussions, but also for managing the conference, which will be held online in 2022.

After welcome comments from Wassim Nashabeh of Roche, a Fellow of CASSS and Chair of the CMC Forum Global Advisory Committee, and Hiroshi Suzuki, Director of PMDA's Regulatory Science Center, discussions began on the following topics Session 1 was held at the Graduate School of Science, Kobe University.

Session 1: Recent Trends in the Regulation of Biopharmaceutical Products

In Session 1, moderated by Kazuhisa Uchida, Professor, Graduate School of Science, Technology and Innovation, Kobe University, and Cecilia Tami, Genentech, regulatory officials from various countries introduced a wide range of topics, including recent regulatory trends, especially for biopharmaceuticals, and emergency responses under the COVID-19 pandemic. The session covered a wide range of topics.

Mr. Yasuhiro Kishioka of the PMDA's Regenerative Medicine Product Review Department introduced recent trends in biopharmaceutical regulatory applications in Japan, the revision of ICH Q-part, and lessons learned from the COVID-19 pandemic.

Ms. Mi Li, Center for Drug Evaluation (CDE), National Medical Products Administration (NMPA), China, provided an overview of the laws and regulations governing drug approval applications in China. She introduced the overall picture of laws and regulations, administrative regulations for biopharmaceuticals, efforts to shorten the review period, and the review of vaccines in emergency situations.

Ingrid Markovic, Center for Biologics Evaluation and Research (CBER), U.S. Food and Drug Administration (FDA), presented on the modernization of the regulatory submission documentation system (KASA). Robin Levis discussed the modernization of vaccine development from Emergency Use Authorization (EUA) to Biologics License Application (BLA). Robin Levis introduced the response from Emergency Use Authorization (EUA) to Biologics License Application (BLA) in vaccine development.

Ms. Veronika Jekerie of the European Medicines Agency (EMA) presented on the efforts and support for innovative manufacturing methods and modalities, the development of toolbox guidelines in the EU, and collaboration between regulatory authorities. She also introduced the development of toolbox guidelines in the EU, collaboration among regulatory authorities, and more.

In the panel discussion, Dr. Wu He of CDE joined the panel to discuss regulatory improvements and collaboration among regulatory authorities regarding expedited review of biopharmaceuticals under the COVID-19 pandemic, support for innovative manufacturing methods and new modalities, further modernization of regulatory submission materials, and the establishment of the Established Condition in ICH Q12. Harmonization of the concept of Established Condition in ICH Q12, harmonization of similarity assessment of biosimilar products, etc. were actively discussed.

Andrew Lennard of Amgen presented methodologies for stability prediction using prior knowledge, specifically, pooling stability data from "like-molecules," utilization of Bayesian statistics, and machine learning models using AI.

In the panel discussion, Mr. Takeshi Omura of Chugai Pharmaceutical joined the panel and had a lively discussion on the expectations and points to be resolved from the standpoint of regulatory authorities and industry in the revision of ICH Q1/Q5C, merits and challenges in setting shelf life by stability modeling, selection of stability batches in continuous production, etc. The panel discussion focused on the health authorities and the industry's position on the revision of the Health Insurance Law.

Session 3: Visible Particles - Mechanism and Mitigation of the Formation and the Control Strategy

In the panel discussion, Antonia Pandelieva of Health Canada joined the panel to discuss insoluble foreign substances in biopharmaceuticals. In particular, there was a lively discussion among authorities and companies on the mechanisms of occurrence, analytical methods, and management strategies for endogenous insoluble foreign substances in biopharmaceuticals.

Session 4: Viral Safety of Biotechnology Products - Changing the Regulatory Landscape, Modalities and Analytical Technologies

Session 4, moderated by Mr. Yoji Sato of the National Institute of Health Sciences and Mr. Andrew Chang of Novo Nordisk, introduced the draft ICH Q5A (R2) guideline that reached Step 2, followed by a discussion among the authorities, companies developing antibody drugs, recombinant After the introduction of the draft ICH Q5A (R2) guideline that reached Step 2, expectations and challenges for the revised guideline in viral clearance strategies and viral safety assessment were discussed from the perspectives of various stakeholders, including the authorities, companies developing products such as antibody drugs and recombinant viral vectors, and contract research organizations (CROs) responsible for viral clearance studies.

After introducing the background and basic principles of the ICH Q5A revision, PMDA Specialist (Bio-Quality) Yo Sakurai explained the major changes and basic concepts of the revised guidelines, including the new product types covered by the revised guidelines, points to be considered in serial production, new test methods, and the use of Prior Knowledge. The main changes and basic concepts of the revised guidelines were explained.

Mr. Shohei Kobayashi of Chugai Pharmaceutical Co., Ltd. introduced the virus clearance strategy, including the use of the modular approach and model virus selection according to the development stage. He also presented his expectations and recommendations for the revised guideline on the use of Prior Knowledge, and introduced his efforts in the production of highly functional antibodies and continuous production processes.

Gilles Chenard of Janssen Vaccines & Prevention B.V. introduced the platform process and viral safety management strategies for adenovirus vector production. He then presented his expectations and recommendations for the use of Prior Knowledge and virus management strategies in terms of viral vectors and products derived from viral vectors, which are newly subject to the revised guidelines.

Munehisa Masuda and Huixing Feng of Merck (BioReliance) explained the impact of the revised guidelines on viral clearance test management strategies, followed by specific introduction of the principles and specifications of molecular biological viral test methods.

In the panel discussion, Christopher Storbeck of Health Canada and Tsutomu Sugihara of Kyowa Kirin joined the panel to discuss the expectations for the use of Prior Knowledge, issues to be resolved, and alternative approaches to molecular biology such as next-generation sequencers, using many questions from the audience as a starting point. A lively discussion ensued on expectations for the use of Prior Knowledge, issues to be resolved, alternative approaches to analytical methods such as next-generation sequencers, and points to keep in mind when utilizing scale-down models in continuous production.

Session 5: Cell & Gene Therapy Products - Showcase both Regulatory and CMC Issues via Case Studies and Recent Challenges Toward Solving Regulatory Issues Session 6: Cell & Gene Therapy Products

In Session 5, moderated by Mr. Yoji Sato of the Regenerative Medicine and Cell Therapy Products Division of the National Institute of Health Sciences and Ms. Christiane Niederlaender of Parexel, companies shared various issues related to cell therapy and gene therapy products from development to post-marketing, and discussed the key points in the quality part of the application materials for regenerative medicine and other products. The PMDA also introduced the quality part of the application materials for regenerative medicine products and the regulations regarding genetically modified organisms (GMOs) in Japan.

Yoko Momonoi of Takeda Pharmaceuticals U.S.A., Inc. spoke about the complexity of manufacturing design and management of allogeneic cell therapy products, which often presents challenges in developing a global strategy due to differing regulatory requirements in each country, He introduced the importance of a risk-based approach.

Masao Kitada and Naoyuki Hanada of Novartis Pharma presented the Cartagena Act, domestic studies of overseas manufactured products, and the Post-Approval Change Management Protocol (PACMP) for change management of marketed products from the perspective of development and post-launch CMC, based on their experience in the development of cell and gene therapy products. The issues and points to keep in mind were introduced, focusing on the Cartagena Act, domestic studies of overseas manufactured products, and the use of the Post-Approval Change Management Protocol (PACMP) in change management of marketed products.

Mr. Atsushi Nishikawa of the PMDA's Regenerative Medicine Product Examination Department introduced the current situation in which there are no guidelines or notifications regarding the composition of application materials for regenerative medicine products, especially the quality part, and applicants prepare application materials based on their own ideas, which has emerged as one of the challenges faced by developers. He then explained the composition of application materials for the quality part of regenerative medical products from the standpoint of an examiner of the regulatory authority.

Mr. Seiichi Kanzaki of the PMDA's Regenerative Medicine Product Examination Division explained the pharmaceutical regulations regarding genetically modified organisms in Japan and introduced the recent improvements in the operation of the Cartagena Act.

Mr. Gentaro Tajima of Pfizer R&D explained the differences between Japan, the U.S., and Europe in regulations regarding GMOs, especially in environmental impact assessments, and the characteristics of the review process, and made suggestions for further improvement of regulations in Japan.

In the panel discussion, Mr. Ryo Kondo of AstraZeneca and Ms. Leslie Nash of Health Canada joined the panel and had a positive discussion on how to solve issues related to the development and post-marketing of regenerative medicine products, and agreed that it is important for industry and government to continue the discussion. Many questions were raised by the audience, indicating the high level of interest in the regulation of regenerative medicine products.

Closing Remarks

(Biopharmaceuticals Committee: Norihito Ueda, Makoto Shinozaki, Tsutomu Sugihara, Yoshinori Kubodera, Nao Nakamura, Teru Nonoyama )

Back to Newsletter Top

TOP