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Regenerative medicine solutions for type 1 diabetes are a rapidly developing field of medical technology. To date, these solutions have been principally cell-based treatments and at present, in Europe, these therapies are regulated under European Union regulations for advanced therapy medicinal products. But now, new emerging technology combining cellular therapy with medical devices is under development. The potential of this novel hybrid model to create a bioartificial pancreas to treat type 1 diabetes is tantalizing. However, incorporating medical devices creates a further layer of regulatory complexity. This article seeks to expose the complexity of this legal and regulatory landscape and demonstrate how evolving technology could challenge the entire existing legal paradigm. We start by summarizing the status of the only established cell-based therapy-transplantation. We set out the regulation of cellular therapies, their classification, and the role of statutory bodies. We examine the bottleneck of therapies moving from bench to bedside, and we consider the additional challenges of products, which use a combination of cells and medical devices. Finally, we argue that for the potential of this rapidly growing area of technology to be realized a seismic shift in how we regulate frontier cellular therapies will be required., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: The aim of this study was to review Japanese laws regarding regenerative medicine and the current status of clinical application of regenerative medicine, to learn about the advantages and problems, and to thereby serve as a reference for measures necessary for the development of regenerative medicine., Background: Regenerative medicine started in 1957 with the transplantation of hematopoietic stem cells, followed by the establishment of embryonic stem cells in 1981 and induced pluripotent stem cells in 2006, and continues to evolve progressively. At the same time, however, problems have emerged due to lax legal regulations, such as the use of treatments that lack scientific evidence., Review Results: The Japanese government enacted two laws to regulate regenerative medicine: the Law to Ensure the Safety of Regenerative Medicine and the Amend the Pharmaceutical Affairs Law in 2013. These laws were enacted with the aim of providing safe regenerative medicine promptly and smoothly and developing many regenerative medicine products. In these laws, regenerative medicine is defined as medical treatment that restores lost functions of damaged organs and tissues with the help of cellular and tissue-based products. Nowadays, there are two major methods of regenerative medicine. One representative method involves the transplantation of devices that activates self-regenerative ability by introducing living cells into patients' body. The other method is the activation and differentiation of endogenous stem cells with cell growth and differentiation factors., Conclusion: The current status of regenerative medicine in the Tohoku region after the enactment of these laws is described in detail. This clarified the advantages and disadvantages associated with regenerative medicine as it is currently practiced in Japan., Clinical Significance: Development of regenerative medicine in dentistry will be advanced by learning about its clinical application in medicine.

Regulations for regenerative medicine for human use, such as cell and gene therapy (CGT), have evolved in accordance with advancements in clinical experience, scientific knowledge, and social acceptance of these technologies. In November 2014, two acts, "The Act on the Safety of Regenerative Medicine" (ASRM) and the "Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act" (PMD Act), came into effect in Japan. The responsibilities of medical institutions in ensuring the safety and transparency of such medical technologies are described under ASRM. The PMD Act provides the option of a new scheme for obtaining conditional and time-limited approval for CGT products. Overall, research and development on CGT products, especially gene therapy products, is progressing. New legislative frameworks have been designed to promote the timely development of new technologies and safe and effective CGT products for Japanese patients., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The unproven stem cell intervention (SCI) industry is a global health problem. Despite efforts of some nations, the industry continues to flourish. In this paper, we call for a global approach and the establishment of a World Health Organization (WHO) Expert Advisory Committee on Regenerative Medicine to tackle this issue and provide guidance. The WHO committee can harmonize national regulations; promote regulatory approaches responsive to unmet patient needs; and formulate an education campaign against misinformation. Fostering an international dialog and developing recommendations that can be adopted by member states would effectively address the global market of unproven SCIs., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Japan's Act on the Safety of Regenerative Medicine (ASRM) created an innovative regulatory framework intended to safely promote the clinical development of stem cell-based interventions (SCBIs) while subjecting commercialized unproven SCBIs to greater scrutiny and accountability. This article reviews ASRM's origins, explains its unprecedented scope, and assesses how it envisions the regulation of SCBIs. This analysis is used to highlight three key insights that are pertinent to the current revision of the ASRM: clarifying how the concept of safety should be defined and assessed in research and clinical care settings; revisiting risk criteria for review of SCBIs; and taking stronger measures to support the transition from unproven interventions to evidence-based therapies. Finally, the article reflects on lessons drawn from Japanese experiences in dealing with unproven SCBIs for international endeavors to regulate SCBIs., Competing Interests: Conflicts of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Induced pluripotent stem cells (iPSC)-based therapies have been hailed as the future of regenerative medicine because of their potential to provide treatment options for most degenerative diseases. A key promise of iPSC-based therapies is the possibility of an autologous transplant that may engraft better in the longer-term due to its compatibility with the patient's immune system. Despite over a decade of research, clinical translation of autologous iPSC-based therapies has been slow-partly due to a lacking pre-defined regulatory path. Here, we outline regulatory considerations for developing an autologous iPSC-based product and challenges associated with the clinical manufacturing of autologous iPSCs and their derivatives. These challenges include donor tissue source, reprogramming methods, heterogeneity of differentiated cells, controls for the manufacturing process, and preclinical considerations. A robust manufacturing process with appropriate quality controls and well-informed, prospectively designed preclinical studies provide a path toward successful approval of autologous iPSC-based therapies., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

With regard to regenerative medicine, the expectations generated over the last two decades and the time involved in developing this type of therapies, together with the availability of devices that allow point-of-care treatments through the rapid isolation of cellular or plasma products from patients in the operating theater, represent the perfect breeding ground for the offering of unproven or unregulated therapies on a global scale. A multidisciplinary approach-one based on the collaboration of institutions that, from the perspective of their area of competence, can contribute to reversing this worrying situation-to this problem is essential. It is a priority for local health authorities to take measures that are adapted to the particular situation and regulatory framework of their respective territory. In this article, the authors present the regenerative medicine action plan promoted by the Andalusian Transplant Coordination (i.e., the action plan for the largest region in Spain), highlighting the aspects the authors believe are fundamental to its success. The authors describe, in summary form, the methodology, phases of the plan, actions designed, key collaborators, important milestones achieved and main lessons they have drawn from their experience so that this can serve as an example for other institutions interested in promoting the ethical use of this type of therapy., (Copyright © 2020 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

The United States Food and Drug Administration (FDA) is responsible for protecting and promoting public health through rules and regulations. Over the past few years, the field of regenerative medicine and cell therapy have garnered significant interest, and this evolving new biology is changing fast and challenging regulatory bodies. The FDA has published a series of guidance documents outlining steps to protect consumers against potentially dangerous and unproven treatments. The agency has offered a grace period for "stem cell clinics" until November 2020 to come into compliance by obtaining Investigational New Drug applications and working to secure premarket approval of their products. With the documentation of hundreds of "stem cell clinics," the FDA needs to enforce the adherence to their outlined standards to protect patients. The aim of this review was to provide an overview of these FDA regulations and some current issues within the industry. The purpose is to educate and inform the musculoskeletal community about the current government regulations of this new expanding biology. LEVEL OF EVIDENCE: Level V, expert opinion., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Despite regenerative medicine (RM) being one of the hottest topics in biotechnology for the past 3 decades, it is generally acknowledged that the field's performance at the bedside has been somewhat disappointing. This may be linked to the novelty of these technologies and their disruptive nature, which has brought an increasing level of complexity to translation. Therefore, we look at how the historical development of the RM field has changed the translational strategy. Specifically, we explore how the pursuit of such novel regenerative therapies has changed the way experts aim to translate their ideas into clinical applications, and then identify areas that need to be corrected or reinforced in order for these therapies to eventually be incorporated into the standard-of-care. This is then linked to a discussion of the preclinical and postclinical challenges remaining today, which offer insights that can contribute to the future progression of RM., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

In the South Korean health technology assessment system, prices of alternative medicines, incremental cost-effectiveness ratios in pharmaco-economic evaluations and patient access improvement systems such as risk-sharing agreements are the most important factors concerning the reimbursement of regenerative medicine (RM). Research and development companies in RM should review the key features of these medicines throughout the product development cycle to increase the probability of successful reimbursement. In addition, the South Korean government should take steps to improve the system to reflect the unique characteristics and value of RM in the reimbursement and pricing policy, to revitalize research and development, and increase patient access.

Cell and gene therapy products are rapidly being integrated into mainstream medicine. Developing global capability will facilitate broad access to these novel therapeutics. An initial step toward achieving this goal is to understand cell and gene therapy manufacturing capability in each region. We conducted an academic survey in 2018 to assess cell and gene therapy manufacturing capacity in Australia and New Zealand. We examined the following: the number and types of cell therapy manufacturing facilities; the number of projects, parallel processes and clinical trials; the types of products; and the manufacturing and quality staffing levels. It was found that Australia and New Zealand provide diverse facilities for cell therapy manufacturing, infrastructure and capability. Further investment and development will enable both countries to make important decisions to meet the growing need for cell and gene therapy and regenerative medicine in the region., (Copyright © 2019 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Interactions between biomaterials and biomaterial-delivering cells and the host tissues are complexly affected by the material itself, the ultrastructure of the overall construct and cells and other bioactive factors involved. The aim of this review is to review the current understanding on the definitions of biocompatibility and current advances in improving biocompatability of tissue-engineered constructs., Recent Findings: Some synthetic materials are associated with more foreign body reactions compared with natural materials; however, they allow fabrication of materials with a great diversity of physical and mechanical properties. Material design strategies can be tailored to mimic the natural extracellular matrix topography. There are also advancements in the pharmacological functionalization of materials with improved angiogenic potential that can lead to better tissue response. Stem cells are also used to improve the tissue response of tissue-engineered materials; however, the recent regulations on regenerative medicine products necessitate significant regulatory approval processes for these., Summary: The biggest challenge faced in translation of tissue-engineered constructs into clinical practice relates to their engraftment and poor tissue integration into the challenging wound bed of the pelvic floor. Biocompatibility of tissue engineered constructs can theoretically be improved by the incorporation of bioactive agents, such as vitamins C or oestradiol.

This article concerns the roles of entrepreneurial scientists in the co-production of life science research and regulation. Regulatory brokerage, defined as a mode of strategic planning and as the negotiation of regulation based on comparative advantage and competition, is expressed in scientific activities that take advantage of regulatory difference. This article is based on social science research in Japan, Thailand, India and the UK. Using five cases related to Japan's international activities in the field of regenerative medicine, I argue that, driven by competitive advantage, regulatory brokerage at lower levels of managerial organization and governance is emulated at higher levels. In addition, as regulatory brokerage affects the creation of regulation at national, bilateral and global levels, new regulation may be based on competition in regulatory advantage rather than on ethical and scientific values. I argue that regulatory brokerage as the basis for regulatory reform bypasses issues that need to be decided by a broader public. More space is needed for international and political debate about the socio-political consequences of the global diversity of regulation in the field of the life sciences.

In March 2017, the US FDA introduced the new Regenerative Medicine Advanced Therapy (RMAT) designation thus recognizing the enormous potential of these medicines and the need for efficient regulatory tools to accelerate their development and their commercial availability. The development of regenerative medicines is very challenging because of their complex and unique nature, especially to the rather unexperienced small- and medium-sized developing enterprises. With the new RMAT designation, FDA aims at providing intensive support to companies developing cell- and tissue-based therapies, tissue-engineering products, and combination treatments. This may also include cell-based products where the genome has been edited by emerging technologies such as CRISPR-Cas9. This article presents the newly launched "Regenerative Medicine Advanced Therapy" (RMAT) designation, outlines existing FDA regulatory tools aiming at expediting approval, and discusses the overall value of these programs. Additionally, recommendations are provided for companies developing these very specific and complex therapies on how and when to consider these tools for an integrated development and regulatory strategy.

The development of biomaterials, medical device components, finished medical products, and 3-D printed and regenerative medicine products is governed by a variety of international and country-specific standards and guidelines. Of greatest importance to planning, executing, and reporting biocompatibility, safety and efficacy studies for most biomaterials and medical components or products are the International Organization for Standardization guidelines, U.S. Pharmacopeial Convention, ASTM International, and Conformité Européenne (European Conformity) marking. The International Medical Device Regulators Forum publishes harmonized standards similar to the International Council for Harmonization. Good Laboratory Practices are applicable and guidance documents for the development of drugs and biologics can also be relevant to biomaterials, medical device components, and medical products and more recently to products produced by 3-D printing or additive manufacturing. Regenerative products may have medical device-based scaffolding and may be treated as biologics, reflecting the cell and tissue components. This compilation of international standards and guidelines provides toxicologic pathologists, toxicologists, bioengineers, and allied professionals with an overview of and source for important regulatory documents that may apply to the nonclinical development of their products.

In the context of regenerative medicine and cellular therapies, the treatment under study often targets a less common disease or condition for which recruitment of a large number of research participants at any given site is challenging, if not impossible. One way to overcome this challenge is with a multi-centre clinical trial. This manuscript first aims to briefly outline the existing ethical, legal and social implications as well as the regulatory frameworks associated with multi-centre regenerative medicine clinical trials. Second, it considers the regulatory limitations and barriers surrounding the initiation of such trials in Canada, the USA and Europe. Third, it concludes with a set of recommendations for facilitating multi-centre clinical trials, at both national and international levels.

Born of the expectations and hype associated with regenerative medicine, there are now numerous clinics around the world selling stem cell-based interventions (SCBI) that have yet to be proven effective or safe, with little to no accounting of the outcomes being collected. In the United States, SCBI are overseen by the U.S. Food and Drug Administration (FDA), but several SCBI clinics have been pushing for policies to expand access and circumvent FDA oversight. Related to this effort, in 2017, Texas passed a bill, HB 810, which allows clinics to provide "investigational stem cell treatments to patients with certain severe chronic diseases or terminal illnesses." In this article, we describe how the new law relates to another deregulation movement, state and federal, the Right to Try laws, the content of HB 810, and the state legislators' intent in passing HB 810.

Purpose: Although most pharmaceutical companies and bio-ventures have not yet created a practical business model or a credible exit thus far, most are expecting potential new business to be derived from regenerative medicine. This article discusses and proposes some ideas regarding a patent strategy for regenerative medicine., Methods: PubMed literature searches were conducted to identify recent reports relevant to regenerative medicine. Information regarding patents and patent applications were obtained from the database service of the Japan Platform for Patent Information on the website of the National Center for Industrial Property Information and Training at https://www.j-platpat.inpit.go.jp/web/all/top/BTmTopEnglishPage and the Japan Patent Office at https://www.jpo.go.jp/index.htm., Findings: The infrastructure of regenerative medicine in Japan is still maturing. Patent protection is important in regenerative medicine considering its special characteristics., Implications: Based on the understanding of the special characteristics of regenerative medicine, this article discusses and proposes some ideas regarding a patent strategy for the field, which is different from that of a typical patent strategy as in the case of a small-molecule drug., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The stem cell and regenerative medicine arena has become increasingly complicated in recent years with thousands of people involved. There are as many as a dozen or more main groups of stakeholders, who together may be viewed as one ecosystem that is now rapidly evolving. The nature of the ecosystem and its evolution have major implications for not just those within it, but also for medicine and society at large. Here, I describe this ecosystem and its evolution, as well as the negative impacts within the ecosystem of a constellation of hundreds of unproven for-profit clinics and related businesses. Finally, I propose approaches for how to positively influence and drive the future of the global stem cell ecosystem.

With its aim to regain the function of organs that are damaged by illness or injury, regenerative medicine has become the global focus of research. To accelerate the development and establishment of sufficient safety measures in regenerative medicine in Japan, the Pharmaceuticals and Medical Devices Act and the Act on Safety of Regenerative Medicine were enacted in 2014. Advancements in regenerative medicine are anticipated to draw attention toward the development of a system that consolidates and uses valuable data from studies performed from premarketing to postmarketing stages. Data gathered from premarketing to postmarketing stages of clinical research would promote new development avenues that would lead to the establishment of appropriate evaluation methods for new regenerative medical products by data validation. Against this background, the Japanese Society for Regenerative Medicine has been working to establish a national consortium for promoting regenerative medicine and constructing a large-scale clinical data registry, called the National Regenerative Medicine Database. This article aims to introduce the current framework of regenerative medicine in Japan, with a particular focus on the activity for establishment of a national consortium for regenerative medicine and the National Regenerative Medicine Database., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The ability of stem cells to self-renew and differentiate into cell types of different lineages forms the basis of regenerative medicine, which focuses on repairing or regenerating damaged or diseased tissues. This has a huge potential to revolutionize medicine. It is anticipated that in future, stem cell therapy will be able to restore function in all major organs. Intensive research has been on-going to bring stem cell therapy from bench to bedside as it holds promise of widespread applications in different areas of medicine. This is also applicable to orthopaedics, where stem cell transplantation could benefit complications like spinal cord injury, critical bone defects, cartilage repair or degenerative disc disorders. Stem cell therapy has a potential to change the field of orthopaedics from surgical replacements and reconstructions to a field of regeneration and prevention. This article summarizes advances in stem cell applications in orthopaedics as well as discussing regulation and ethical issues related to the use of stem cells.

Perpetual debate regarding the delicate balance between access and innovation and the protection of the public health and safety dominate discussions of the United States Food and Drug Administration ("FDA"). Established chiefly as a command and control federal administrative agency, iterative changes in legislation have shaped the FDA's activity in drug, biologic, and medical device regulation over the course of the last one hundred plus years. The most recent fundamental reframing of the agency's authority and directive presented itself in the 21 st Century Cures Act, reflecting an important role for patient perspectives in the regulatory process. This Article explores recent developments in patient-focused product development efforts at the FDA and offers modest insights on the increasing role of patients, and patient advocacy groups, in agency decision-making. The Article terms this era "21 st century citizen pharma."

Legislation for expedited-approval pathways and programmes for drugs, biologics or medical devices has been enacted for rapid commercialization of innovative products in the United States of America (USA) and the European Union (EU). However, less innovative products are increasingly benefitting from these expedited-approval pathways, and obligations to collect and report post-marketing data on approved products are being bypassed frequently. The Japanese government recently enacted legislation for a new conditional and time-limited approval pathway dedicated to regenerative medicine products. The current study examines this new legislation and compares it with existing US and EU regulatory frameworks, with a particular focus on how it addresses the limitations of existing systems. Regulations, guidance documents and approval information were gathered from the websites of the respective authorities in the USA, the EU and Japan, and the systems were categorized through qualitative analysis. The pathways and programmes from each region were categorized into four groups, based on the requirement of pre- or post-marketing clinical data. Expedited-approval pathways in the USA and the EU provide similar qualification criteria, such as severity of target disease; however, such criteria are not specified for the new pathway in Japan. Only the Japanese pathway stipulates a time limitation on exceptional approval, requiring post-marketing study for conditional and time-limited products. Continuous improvement is necessary to solve previously addressed issues within the expedited-approval pathways and programmes and to ensure that innovative medical products are rigourously screened, but also readily available to patients in need. The time limitation of conditional approval could be a potential solution to some of these problems. Copyright © 2017 The Authors. Tissue Engineering Regenerative Medicine published by John Wiley & Sons, Ltd., (Copyright © 2017 The Authors. Tissue Engineering Regenerative Medicine published by John Wiley & Sons, Ltd.)

Cellular therapies have moved to the forefront based upon promising results from clinical trials using both chimeric antigen receptor T lymphocytes to treat leukemia and other cell types to restore structure and function to tissues that have been damaged by disease or physical injury. The pace at which these treatments have evolved has posed a regulatory challenge to agencies, such as the Food and Drug Administration (FDA). This chapter describes how a specific regulatory strategy was developed and how it has evolved in response to the demand for these new therapies.

Current European regulations hinder the compilation of the evidence that would be required to bring safe and effective autologous stem cell-based interventions (SCBIs) into standard clinical care. European agencies have expanded their regulations to cover all new SCBIs and research. They establish demanding conditions for cell retrieval, processing, and application. Drawing on empirical sociological findings from the implementation of the first phase III stem cell clinical trial in Europe, this article examines ethical problems effected by that policy, such as that the costs of bringing treatments to market means new autologous SCBIs may remain untested and that this plays in favor of the growing direct-to-consumer market, and that the research pathways in regenerative medicine and the role of clinician-scientists in developing new treatments are restricted, because the regulations are biased to enable specific SCBIs that are of interest to industry. This situation contradicts the moral and social concerns in favor of new treatments and patient interests, which the regulations supposedly safeguard. To align the aims and effects of policy better, European regulatory authorities should reconfigure their regulations to advance a fair and effective governance regime that allows pursuit of all promising SCBIs.

Many countries have identified regenerative medicine as a strategic priority, and have thus launched a range of initiatives to facilitate innovation in the field. This perspective paper argues that several initiatives involve resource distributions that could impinge on widely accepted egalitarian notions of fairness and justice that underpin current healthcare systems. Specifically, this paper focuses on five initiatives, and argues that these initiatives reflect a largely unacknowledged utilitarian perspective on distributive justice. The intention of this paper is not to argue against these initiatives, but rather to stimulate an open discussion on what qualifies as a just and fair system of resource distribution, so that the regenerative medicine field can responsibly deliver on its clinical potential.

The Paolo Macchiarini case has several ethical ramifications. Professor Macchiarini, formerly of the Karolinska Institutet (KI), became famous for the tracheal surgeries he conducted between 2008 and 2014. His rapid rise to fame was followed by an almost equally rapid fall from grace as official reports, articles in newspapers and television programmes revealed several aspects related to misconduct in his curriculum vitae, professional practices and publishing-related activity. Formal misconduct reports issued by four KI co-workers in late 2014, then again in 2016, coupled with social scandals, including the tricking of a famous US television newscaster into a false marriage, a previous arrest in Italy for apparent bribery, and acute narcissism, all tainted Macchiarini's legend. In the short space of just two years, Macchiarini was no longer remembered for the revolutionary changes he had claimed to have brought about in stem cell research and regenerative medicine. Instead, at least seven dead patients later, Macchiarini faces potential aggravated manslaughter charges and an uphill battle to save his published research, now shrouded in scandal and scientific doubt, from being retracted and scratched out from the list of verified medical science. This paper examines some of the possible ethical ramifications of the Macchiarini case.

The government of India has heavily promoted research and development in regenerative medicine together with domestic innovation and business development initiatives. Together, these promise a revolution in healthcare and public empowerment in India. Several national and transnational linkages have emerged to develop innovative capacity, most prominently in stem cell and cord blood banking, as well as in gene therapy, tissue engineering, biomaterials and 3D printing. However, challenges remain of achieving regulatory oversight, viable outputs and equitable impacts. Governance of private cord blood banking, nanomaterials and 3D bioprinting requires more attention. A robust social contract is also needed in healthcare more generally, so that participation in research and innovation in regenerative medicine is backed up by treatments widely accessible to all.

Two Japanese regulatory agencies, the Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency announced the implementation of a new review system called 'Conditional Approval,' specifically for the emerging field of regenerative medicine, in an amendment to the Pharmaceutical Affairs Act in 2014. Regenerative medicine was regulated in the category of 'Medical Devices' prior to the amendment and was not covered by the Relief Service, a system that provides financial aid to people who have experienced an adverse drug reaction and developed serious side effects as a result. Through the amendment, regenerative medicine is defined as a new category and is covered by the Relief Service under the amended Pharmaceutical Affairs Act, called the 'Act on Securing Quality, Efficacy and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics' (PMD Act). This amendment allows the use of Relief Service data for pharmacovigilance activities, making the Relief Service the third adverse drug reaction reporting route in addition to the existing reporting routes from marketing authorization holders and healthcare providers. For optimum incorporation and use of this Relief Service data, earlier access should be allowed even before the reports from the Pharmaceuticals and Medical Devices Agency to the Ministry of Health, Labour and Welfare are finalized, which is mandatory under the current PMD Act.