[Contribution] For Advanced Regenerative Medicine, the Premise of Expanding Access Is Safety Management

After the Advanced Regenerative Bio Act was enacted in 2019, the author participated in the work of drafting its enforcement decree and enforcement rules. It was a time when public opinion had frozen over due to the Invossa scandal. What we grappled with the longest in the conference room was not technology or industry, but a single boundary line: up to where is research, and from where is it treatment? And the moment that boundary is crossed, who must take responsibility for what?

The risks of medicine dealing with cells and genes surface late, sometimes only after a very long time. That is why the law established safeguards such as prior review, designation of implementing institutions, and long-term follow-up investigation. The basic idea of this law was to permit it under certain requirements rather than banning it outright, and to continuously manage it thereafter.

◆ Significance of the 2024 legal amendment

The center of gravity of this system shifted once with the February 2024 legal amendment. This is the advanced regenerative medicine treatment system that took effect in February the following year. Until then, advanced regenerative medicine was possible only within the framework of clinical research. Even as evidence on safety and efficacy accumulated, there was no institutional pathway for patients to receive it as treatment domestically, and that void was filled by overseas expedition treatment and underground procedures.

The amended law opened a path for patients with serious diseases that lack alternative treatments or threaten life, rare diseases, and other intractable diseases to receive treatment domestically in accordance with a treatment plan that has received a suitability notice from the review committee. It changed the structure of regulation from a method of blocking treatment at the source to a method of reviewing safety and efficacy and managing it even after treatment.

The first treatment plan approved this past April is the first such case. It is a treatment in which autologous immune cells are administered to a patient in complete remission of EBV-positive extranodal NK/T-cell lymphoma with a high risk of recurrence, to prevent recurrence and induce long-term survival. It is carried out on 15 patients at Yeouido St. Mary's Hospital, with a treatment cost of 76 million won. A performance-linked method that refunds the entire cost if recurrence occurs within 5 years was also applied.

◆ Core of the 2nd Basic Plan

The 2nd Basic Plan for Advanced Regenerative Medicine and Advanced Biopharmaceuticals, deliberated and resolved by the government this past July 21, is a plan that accelerates this transition. Its core lies in expanding patients' access to treatment while simultaneously establishing a safety management system commensurate with the expanded system.

From this month, the government is leading multi-institution clinical research on knee osteoarthritis, intractable chronic pain, and recurrent glioblastoma, for which there is high demand for overseas expedition treatment. The blood cancer project is also awaiting re-review after supplementing its plan. Rather than unconditionally permitting procedures that had been performed overseas, the state will secure evidence of safety and efficacy through clinical research and then connect it to domestic treatment.

The risk level of cultured autologous immune cells, for which safety evidence and use cases have accumulated, is being adjusted from medium risk to low risk. When adjusted to low risk, one can apply for treatment plan review without separate preceding clinical research, increasing patients' access to treatment. However, cell culture must still be performed only at licensed cell processing facilities even after the risk adjustment. This is a method of easing regulation on parts where safety has been confirmed while continuing to control processes that require quality management.

The supply route is also expanded so that cell processing facilities can be provided with and utilize raw-material cells collected and stored by other domestic institutions such as cord blood banks. Subcommittees according to risk level will be established within the review committee, and review guidelines will be prepared based on accumulated review cases. The direction is to widen entry pathways to expand access while simultaneously enhancing the expertise and predictability of the review.

◆ Safety management accompanying expanded access

The expansion of regenerative medicine institutions should be viewed in the same context. The government plans to expand regenerative medicine institutions from 183 in 2025 to 400 by 2030. As of this past June, 223 institutions have already been designated. To broaden the base on which patients can receive advanced regenerative medicine domestically, the number of medical institutions able to participate in research and treatment must increase.

However, simply increasing the number of institutions does not substantively raise patients' access. Designation is merely confirmation that facilities, equipment, personnel, and other statutory requirements have been met; it does not mean the institution is actually carrying out approved research or treatment. Compared to the increase in designated institutions, actual participation in research and treatment is limited, and some institutions are using the mere fact of designation as a promotional tool. Last year alone, false and exaggerated advertisements related to regenerative medicine detected in online monitoring reached 246 cases.

Therefore, management after designation must be strengthened to the same extent that designated institutions are expanded. The government plans to mandate that regenerative medicine institutions submit a clinical research or treatment plan within 1 year of designation, and to establish grounds to revoke the designation if a plan is not submitted within that period. It will introduce a 3-year designation renewal system to comprehensively check research and treatment participation records, completion of training, and violations of laws and regulations.

The information patients can verify must also change. What should be disclosed is not simply whether an institution has been designated by the Ministry of Health and Welfare, but what research and treatments the institution has been approved for and what it is actually carrying out. The government's decision to disclose approved treatments, implementing institutions, and treatment costs through the Advanced Regenerative Medicine Portal is an important device to protect patients' right to know and right to self-determination.

The detailed criteria of the designation renewal system need to be carefully designed. Evaluating participation records by mere case counts could disadvantage institutions in rare-disease fields with extremely few patients. Evaluation criteria reflecting the special nature of research and treatment, and objection procedures for denial of re-designation, must be clearly established in the law and subordinate legislation.

◆ The importance of trust in safety management

This Basic Plan is not a plan to uniformly ease or strengthen regulation. It is a plan that makes entry easy for low-risk fields where safety evidence has accumulated, continues to control unverified risks and processes requiring quality management, and strengthens follow-up management and information disclosure to the same extent that institutions and treatments increase. It views expanded access and safety management not as opposing values but as two axes forming a single system.

What we discussed the longest in the conference room drafting the enforcement decree and rules 6 years ago was also not the question of whether to permit the technology, but of under what procedures and responsibilities the technology should reach patients. This question has become even more important now that the treatment system has been introduced and designated institutions are increasing. If patients cannot accurately know the basis and risks of treatment and the experience of implementing institutions, institutional expansion of access is unlikely to lead to substantive treatment opportunities.

The treatment opportunities of advanced regenerative medicine should be further broadened going forward. However, for that expansion to be sustained, patients must be able to choose treatment based on sufficient information, and the state must be able to confirm safety even after treatment. Only when the system that broadens access and the responsibility that safeguards safety operate together can advanced regenerative medicine finally establish itself as trusted treatment.

|Contribution| Attorney Lee Seo-hyung, Daeryun LLC (Law Firm)

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