July 2024
Series Articles of the Regenerative Medicine Dual Legislation (2) – Analysis of the Conditional Approval System for Regenerative Medicine Product
On June 4, 2024, Taiwan’s Legislative Yuan completed the third reading and passed the “Regenerative Medicine Act” and the “Regenerative Medicine Product Regulations” (hereinafter collectively referred to as the “Regenerative Medicine Dual Acts”
[1]
), and the Regenerative Medicine Dual Acts have been promulgated by the President on June 19, 2024. The Regenerative Medicine Dual Acts will officially come into effect on the implementation date to be announced by the Executive Yuan. Through the enactment of the regulations at law level, the Regenerative Medicine Dual Acts are expected to promote the development of regenerative medicine in Taiwan.
Before the enactment of the Regenerative Medicine Dual Acts, regenerative medicine technologies were mainly regulated through the "Regulations Governing the Application or Use of Specific Medical Techniques or Examinations, or Medical Devices" authorized by the Medical Care Act, and the regenerative medicine products were regulated by the Pharmaceutical Affairs Act and the “Guidance on Registration for Human Cell Therapy Products” and “Guidance on Registration for Human Gene Therapy Products” announced by the Ministry of Health and Welfare (hereinafter referred to as the "MoHW"). After the enactment of the Regenerative Medicine Dual Acts, it continues to adopt a dual-track management model of medical technique and drugs, managing the regenerative medicine technologies and pharmaceuticals through the "Regenerative Medicine Act" and the "Regenerative Medicine Product Regulations" respectively. The “Regenerative Medicine Product Regulations" defines regenerative medical products as medical products containing genes, cells, and their derivatives for human use, which are drugs under the Pharmaceutical Affairs Act.
The “Regenerative Medicine Product Regulations", which is similar to the provisions of the Pharmaceutical Affairs Act, requires pharmaceutical firms to apply for inspection and registration and obtain a drug permit license from the MoHW before manufacturing and importing regenerative medical products. However, considering the complicated and lengthy process for the drug launch, for example, the inspection and registration review of new biopharmaceuticals takes an average of more than eight months [2] , it is too slow to meet a pressing need of the patients. To ensure the rights and interests of patients with urgent medical needs to use the regenerative medical product, the legislation stipulates a conditional approval system in the “Regenerative Medicine Product Regulations", which refers to the legal systems of Japan and the United States. The central competent authority, namely the MoHW, may grant conditional approval for up to five years to regenerative medicine products applied for inspection and registration for life-threatening or severely disabling diseases after completing Phase II clinical trials, completing risk and benefits review, demonstrating safety and preliminary efficacy, in order to improve the accessibility of medicines to patients as soon as possible.
As for which types of diseases meet the definition of "life-threatening or severely disabling diseases," considering the huge investment in the research and development process of regenerative medical products, and in order to facilitate pharmaceutical firms to evaluate the possibility of obtaining a conditional approval in advance, pharmaceutical firms are allowed to apply for determination from the MoHW before applying for inspection and registration.
Since conditional approvals are temporary measures, in order to properly weigh the efficacy and safety of the drug for patients, the MoHW is required to seek the approval of the Regenerative Medicine Review Committee before granting conditional approval. The "Regenerative Medicine Product Regulations" clearly stipulates that the MoHW should attach the conditions including:
(1) Completing efficacy verification tests, submitting test reports regularly or within a specified period;
(2) Proposing fee structures and payment methods for the products;
(3) Providing remedies for patients using medicine products and experiencing adverse reactions leading to death, disability, or serious illness, and
(4)Other conditions specified by the central competent authority.
After the MoHW grants a conditional approval, the MoHW may revoke the approval if the pharmaceutical firms fail to fulfill the attached condition or if there are serious safety concerns after assessment. However, if the pharmaceutical firms fulfill the conditions, they may further apply to the MoHW for inspection and registration and obtain a formal drug permit license in order to switch from a temporary measure to a general license mode.
Currently, MoHW has only approved a few drug licenses for regenerative medical products from foreign pharmaceutical firms, including CAR-T cell therapy product Kymriah and gene therapy products Zolgensma and Luxturna from Novartis [3] . However, there are still hundreds of clinical trials of cell therapy and gene therapy products approved by the MoHW. Through the establishment of the conditional approval system, some regenerative medical products, which have completed Phase II clinical trials and have undergone risk review, are expected to be launched into the market earlier through this channel. In addition to increasing the accessibility of domestic regenerative medical products and providing more diversified treatment methods to benefit patients with major diseases, these systems can also speed up the time to market of regenerative medical products to a certain extent, so as to improve the ecosystem of regenerative medicine, provide incentives to investors in the industry and can further promote the development of Taiwan's regenerative medicine industry.
In order to effectively implement the conditional approval system for regenerative medical products, in the future there will be guidelines regarding the application conditions, application documents and information, review procedures, approval standards, fees and other related matters for conditional approvals that will be formulated by the MoHW as sub-laws to establish practical operating standards, and our firm will continue to monitor relevant regulatory developments.
[1] For an introduction to the newly passed Regenerative Medicine Dual Acts, please refer to our article“ Series Articles of the Regenerative Medicine Dual Legislation (1) – Taiwan's Legislative Yuan Passed the Regenerative Medicine Dual Legislation ”
[2] According to the meeting slide from the Center for Drug Evaluation, the average review period for new drug inspection and registration of biopharmaceuticals and radioactive drugs in 2023 was 265 days. https://www.cde.org.tw/news/news_more?id=404 (Last visited on July 8, 2024).
[3] Refer to the Ministry of Economic Affairs, 2023 Cell and Gene Therapy Industry Review :https://www.moea.gov.tw/MNS/doit/industrytech/IndustryTech.aspx?menu_id=13545&it_id=528; Taiwan Food and Drug Administration, Regenerative Medicine Product Regulations and approval status in Taiwan: https://www.fda.gov.tw/TC/siteList.aspx?sid=12080 (last visited on July 8, 2024)
Before the enactment of the Regenerative Medicine Dual Acts, regenerative medicine technologies were mainly regulated through the "Regulations Governing the Application or Use of Specific Medical Techniques or Examinations, or Medical Devices" authorized by the Medical Care Act, and the regenerative medicine products were regulated by the Pharmaceutical Affairs Act and the “Guidance on Registration for Human Cell Therapy Products” and “Guidance on Registration for Human Gene Therapy Products” announced by the Ministry of Health and Welfare (hereinafter referred to as the "MoHW"). After the enactment of the Regenerative Medicine Dual Acts, it continues to adopt a dual-track management model of medical technique and drugs, managing the regenerative medicine technologies and pharmaceuticals through the "Regenerative Medicine Act" and the "Regenerative Medicine Product Regulations" respectively. The “Regenerative Medicine Product Regulations" defines regenerative medical products as medical products containing genes, cells, and their derivatives for human use, which are drugs under the Pharmaceutical Affairs Act.
The “Regenerative Medicine Product Regulations", which is similar to the provisions of the Pharmaceutical Affairs Act, requires pharmaceutical firms to apply for inspection and registration and obtain a drug permit license from the MoHW before manufacturing and importing regenerative medical products. However, considering the complicated and lengthy process for the drug launch, for example, the inspection and registration review of new biopharmaceuticals takes an average of more than eight months [2] , it is too slow to meet a pressing need of the patients. To ensure the rights and interests of patients with urgent medical needs to use the regenerative medical product, the legislation stipulates a conditional approval system in the “Regenerative Medicine Product Regulations", which refers to the legal systems of Japan and the United States. The central competent authority, namely the MoHW, may grant conditional approval for up to five years to regenerative medicine products applied for inspection and registration for life-threatening or severely disabling diseases after completing Phase II clinical trials, completing risk and benefits review, demonstrating safety and preliminary efficacy, in order to improve the accessibility of medicines to patients as soon as possible.
As for which types of diseases meet the definition of "life-threatening or severely disabling diseases," considering the huge investment in the research and development process of regenerative medical products, and in order to facilitate pharmaceutical firms to evaluate the possibility of obtaining a conditional approval in advance, pharmaceutical firms are allowed to apply for determination from the MoHW before applying for inspection and registration.
Since conditional approvals are temporary measures, in order to properly weigh the efficacy and safety of the drug for patients, the MoHW is required to seek the approval of the Regenerative Medicine Review Committee before granting conditional approval. The "Regenerative Medicine Product Regulations" clearly stipulates that the MoHW should attach the conditions including:
(1) Completing efficacy verification tests, submitting test reports regularly or within a specified period;
(2) Proposing fee structures and payment methods for the products;
(3) Providing remedies for patients using medicine products and experiencing adverse reactions leading to death, disability, or serious illness, and
(4)Other conditions specified by the central competent authority.
After the MoHW grants a conditional approval, the MoHW may revoke the approval if the pharmaceutical firms fail to fulfill the attached condition or if there are serious safety concerns after assessment. However, if the pharmaceutical firms fulfill the conditions, they may further apply to the MoHW for inspection and registration and obtain a formal drug permit license in order to switch from a temporary measure to a general license mode.
Currently, MoHW has only approved a few drug licenses for regenerative medical products from foreign pharmaceutical firms, including CAR-T cell therapy product Kymriah and gene therapy products Zolgensma and Luxturna from Novartis [3] . However, there are still hundreds of clinical trials of cell therapy and gene therapy products approved by the MoHW. Through the establishment of the conditional approval system, some regenerative medical products, which have completed Phase II clinical trials and have undergone risk review, are expected to be launched into the market earlier through this channel. In addition to increasing the accessibility of domestic regenerative medical products and providing more diversified treatment methods to benefit patients with major diseases, these systems can also speed up the time to market of regenerative medical products to a certain extent, so as to improve the ecosystem of regenerative medicine, provide incentives to investors in the industry and can further promote the development of Taiwan's regenerative medicine industry.
In order to effectively implement the conditional approval system for regenerative medical products, in the future there will be guidelines regarding the application conditions, application documents and information, review procedures, approval standards, fees and other related matters for conditional approvals that will be formulated by the MoHW as sub-laws to establish practical operating standards, and our firm will continue to monitor relevant regulatory developments.
[1] For an introduction to the newly passed Regenerative Medicine Dual Acts, please refer to our article“ Series Articles of the Regenerative Medicine Dual Legislation (1) – Taiwan's Legislative Yuan Passed the Regenerative Medicine Dual Legislation ”
[2] According to the meeting slide from the Center for Drug Evaluation, the average review period for new drug inspection and registration of biopharmaceuticals and radioactive drugs in 2023 was 265 days. https://www.cde.org.tw/news/news_more?id=404 (Last visited on July 8, 2024).
[3] Refer to the Ministry of Economic Affairs, 2023 Cell and Gene Therapy Industry Review :https://www.moea.gov.tw/MNS/doit/industrytech/IndustryTech.aspx?menu_id=13545&it_id=528; Taiwan Food and Drug Administration, Regenerative Medicine Product Regulations and approval status in Taiwan: https://www.fda.gov.tw/TC/siteList.aspx?sid=12080 (last visited on July 8, 2024)
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Series Articles of the Regenerative Medicine Dual Legislation (4) – Draft Announcement of Certain Subsidiary Regulations Under the Regenerative Medicinal Products Act (Taiwan) Series Articles of the Regenerative Medicine Dual Legislation (1) – Taiwan's Legislative Yuan Passed the Regenerative Medicine Dual Legislation Series Articles of the Regenerative Medicine Dual Legislation (3) – The Impact of the Regenerative Medicine Dual Acts on the Therapy and Drug Development of Rare Diseases
