The ACTO Times, Editorial Office

Abstract

South Korea has established a distinctive regulatory architecture for cell and gene therapies that links advanced regenerative medicine, institution-based clinical research, medicinal-product development, and long-term safety oversight. The central framework was introduced through the Act on the Safety of and Support for Advanced Regenerative Medicine and Advanced Biological Products, enacted in 2019 and implemented in 2020. The system distinguishes advanced regenerative medicine conducted within designated medical institutions from advanced biological products developed as standardized medicinal products. Clinical research is subject to risk-based review, institutional qualification, participant protection, and safety monitoring, while commercial cell and gene therapy products remain subject to manufacturing, clinical-trial, marketing-authorization, and post-marketing requirements. A major amendment implemented in February 2025 introduced advanced regenerative medicine treatment as a separate legal category, enabling selected interventions to be provided outside clinical research under reviewed treatment plans. This report summarizes the structure of the Korean framework, its expedited product-development mechanisms, post-marketing surveillance system, and continuing challenges related to evidence generation, patient access, affordability, and the distinction between regulated medical treatment and medicinal-product authorization.

Keywords: cell therapy; gene therapy; advanced regenerative medicine; advanced biological products; South Korea; regulation

Introduction

Cell and gene therapies present regulatory challenges that differ substantially from those associated with conventional pharmaceutical products. Their clinical performance may be influenced by donor characteristics, cell source, genetic modification, manufacturing variability, storage, transport, administration procedures, and the clinical expertise of the treating institution. Potential risks may include immune toxicity, tumorigenicity, unintended genetic alterations, contamination, abnormal differentiation, and adverse effects that emerge long after treatment.

South Korea introduced a dedicated framework to support the development of these therapies while strengthening patient protection and long-term safety management. The Act on the Safety of and Support for Advanced Regenerative Medicine and Advanced Biological Products, frequently abbreviated in published literature as the ARMAB Act, was enacted in August 2019 and implemented in August 2020 [1,2].

The legislation consolidated several previously fragmented regulatory functions and created a legal distinction between advanced regenerative medicine and advanced biological products.

This distinction is fundamental. Advanced regenerative medicine concerns the clinical application of cell, gene, tissue-engineering, or convergence-based technologies within qualified medical institutions. Advanced biological products are developed as defined medicinal products and include cell therapy products, gene therapy products, tissue-engineered products, and advanced biological combination products [1,2]. Although both domains are addressed within the same legislative architecture, they follow different review pathways and should not be treated as interchangeable routes to clinical use.

An integrated but differentiated regulatory framework

The Korean framework distributes responsibilities primarily between the Ministry of Health and Welfare and the Ministry of Food and Drug Safety. The Ministry of Health and Welfare is principally associated with the administration of advanced regenerative medicine in medical institutions, whereas the Ministry of Food and Drug Safety oversees advanced biological products, product clinical trials, manufacturing controls, marketing authorization, and post-authorization safety management [1,2,4].

Published analyses describe this structure as an integrated system with two connected regulatory domains. The first domain covers institution-based regenerative medicine, initially centred on clinical research and now also including a regulated treatment category. The second domain covers standardized products intended for manufacture, distribution, and commercial authorization [1–4].

The classification of an intervention cannot be determined merely by the presence of cells or genetic material. The intended mode of development, degree of manipulation, manufacturing model, clinical setting, and proposed distribution all influence whether an intervention is treated as advanced regenerative medicine or as an advanced biological product. This distinction becomes particularly important when an initially individualized hospital-based intervention develops into a reproducible and scalable product.

Advanced regenerative medicine clinical research

Advanced regenerative medicine clinical research is intended to provide a controlled pathway for investigating regenerative interventions in patients while generating evidence on safety and clinical performance. Published descriptions of the Korean system indicate that such research must be conducted in designated medical institutions with appropriate facilities, personnel, governance, and safety-management capacity [1,2].

Research plans undergo centralized scientific and ethical evaluation. The review considers the scientific rationale, anticipated benefits, foreseeable risks, participant-selection criteria, study design, cell-processing procedures, and measures for managing adverse events. The framework applies a risk-based approach, with higher-risk studies receiving more extensive scrutiny. High-risk research requires an additional assessment by the Ministry of Food and Drug Safety after review by the relevant regenerative medicine review committee [1,4].

This system should not be interpreted as a reduced form of clinical-trial oversight. Regenerative medicine research remains subject to informed consent, protocol compliance, data integrity, adverse-event reporting, participant protection, and, where appropriate, long-term follow-up. The need for long-term monitoring is especially important for genetically modified cells, stem-cell-derived interventions, and products capable of persisting or proliferating after administration [1,2].

Clinical research also remains distinct from routine medical treatment. Under the original framework implemented in 2020, advanced regenerative medicine was primarily accessed through approved research protocols. The research pathway was designed to generate knowledge and evaluate safety and effectiveness rather than to permit unrestricted clinical provision of unproven interventions [1].

Introduction of advanced regenerative medicine treatment

A major regulatory development occurred through an amendment that introduced advanced regenerative medicine treatment as a separate legal category. The amendment became effective in February 2025 and was subsequently examined in a 2026 peer-reviewed analysis by Yoon and colleagues [3].

The new treatment category creates a route through which selected advanced regenerative medicine interventions may be provided outside a clinical-research protocol. However, this pathway should not be characterized as general permission to offer unapproved cell or gene therapies. Treatment remains dependent on institutional qualification, review of the proposed treatment plan, safety-management arrangements, informed consent, and continuing oversight [3].

The distinction between clinical research and advanced regenerative medicine treatment is important. Clinical research is designed primarily to generate systematic evidence according to a research protocol. Advanced regenerative medicine treatment is provided as medical care under a reviewed treatment plan. Nevertheless, the introduction of a treatment pathway does not automatically establish the same level of evidence as conventional medicinal-product marketing authorization.

Similarly, approval of an institution-specific treatment plan does not mean that the underlying cells, vector, manufacturing process, or technology may be manufactured and distributed nationally as an authorized medicinal product. Commercial distribution remains subject to the separate advanced biological product pathway administered by the Ministry of Food and Drug Safety [3,4].

The new treatment category is intended to improve access for patients with serious or difficult-to-treat conditions, but it also introduces regulatory and ethical questions. These include the level of evidence required before treatment, the consistency of review decisions, long-term follow-up, patient understanding of uncertainty, financial burden, and the prevention of therapeutic misconception [3]. Since the pathway only became operational in 2025, its effects on clinical outcomes, patient access, healthcare expenditure, and product development remain too recent for definitive evaluation.

Advanced biological products and medicinal-product authorization

Cell and gene therapies intended to be manufactured and marketed as standardized products are regulated as advanced biological products. This pathway follows the general lifecycle of medicinal-product development, including chemistry, manufacturing and controls, nonclinical studies, clinical-trial authorization, clinical development, marketing-authorization review, and post-approval surveillance [1,4].

Manufacturing control is particularly important because the clinical characteristics of a cell or gene therapy may be altered by relatively small changes in raw materials, cell culture, genetic modification, purification, cryopreservation, transport, or administration. Developers must therefore establish appropriate controls for identity, purity, viability, potency, sterility, genetic stability, donor eligibility, adventitious agents, and batch-to-batch consistency [4,6].

For gene-modified therapies, additional considerations may include vector design, biodistribution, persistence, off-target effects, insertional mutagenesis, shedding, immune responses, and the possibility of unintended germline exposure. Stem-cell-derived products may require careful assessment of differentiation status, residual undifferentiated cells, genetic abnormalities, tumorigenicity, and functional potency [5,6].

The Ministry of Food and Drug Safety evaluates the totality of manufacturing, nonclinical, and clinical evidence. Marketing authorization applies to a defined product, indication, manufacturing process, and conditions of use. It is therefore broader than approval of a treatment plan at an individual medical institution, but it also requires a more extensive and standardized evidence package.

Expedited development and conditional approval

South Korea has introduced expedited mechanisms for eligible advanced biological products intended to address serious, life-threatening, or rare diseases. The mechanisms described in the published literature include customized review, priority review, and conditional approval [1,4]. Customized review allows portions of the application to be evaluated progressively according to the developer’s preparation schedule.

Priority review gives an eligible product precedence over standard applications. Conditional approval may permit earlier authorization on the basis of preliminary clinical evidence, with additional or confirmatory studies required after marketing [1,4].

These mechanisms are designed to reduce unnecessary delays where patients have substantial unmet medical needs. However, expedited development does not eliminate the requirements for manufacturing quality, clinical justification, risk management, or post-authorization evidence. Conditional approval transfers part of the evidentiary burden to the post-marketing period rather than removing that burden.

This approach can be particularly relevant to CGTs because conventional large, randomized trials may be difficult for rare diseases or highly individualized products. Nevertheless, reliance on smaller studies, surrogate endpoints, or early clinical outcomes increases uncertainty at the time of authorization. Effective post-marketing surveillance and timely completion of confirmatory studies are therefore essential.

Post-marketing surveillance and long-term follow-up

Long-term safety oversight is one of the most prominent elements of the Korean framework. The biological effects of cell and gene therapies may persist for years, and some complications may not be detected during the relatively limited duration of pre-authorization clinical trials [1,5].

The Korean system includes mechanisms for long-term follow-up, electronic safety reporting, traceability, periodic safety reporting, re-examination, and re-evaluation. A comparative study of post-marketing surveillance frameworks reported that South Korea’s principal approaches for CGT products include periodic safety update reports, re-examination, and re-evaluation [5].

Long-term surveillance is particularly relevant for gene therapies, genetically modified cells, and stem-cell products. Monitoring should be capable of identifying delayed malignancy, persistent immune reactions, loss of therapeutic effect, abnormal tissue formation, or complications related to the administered cells or vector.

The effectiveness of post-marketing surveillance depends not only on formal requirements but also on the completeness and quality of the collected data. Patient retention, interoperability between databases, accurate product traceability, standardized adverse-event definitions, and coordination between medical institutions, manufacturers, and regulators remain important practical considerations [1,5].

Pricing, reimbursement, and patient access

Regulatory authorization does not by itself guarantee patient access. CGTs are frequently associated with high manufacturing and treatment costs, small eligible populations, limited long-term evidence, and uncertainty regarding the duration of therapeutic benefit. These features create substantial challenges for health-technology assessment, pricing, and reimbursement [4].

South Korea’s reimbursement system uses health-technology and economic assessments similar in several respects to those applied in European countries. Risk-sharing agreements may be used to manage financial and clinical uncertainty, particularly for high-cost therapies with limited evidence at launch [4].

However, different access questions arise under the advanced regenerative medicine treatment pathway. Institution-based treatment may improve access before a standardized product completes conventional development, but it can also transfer greater uncertainty or financial responsibility to patients. Clear communication is therefore needed regarding the difference between clinical research, regulated medical treatment, conditional product authorization, and full marketing authorization.

Continuing challenges

The first challenge is maintaining a clear boundary between institution-based treatment and commercial product development. A therapy may begin as an individualized intervention but later become reproducible and scalable. Regulators must determine when continued use under a treatment plan remains appropriate and when the intervention should proceed through the medicinal-product pathway.

The second challenge is evidentiary consistency. Different institutions may possess different manufacturing capabilities, clinical expertise, and follow-up systems. Standardized outcome measures, transparent review criteria, and common data-reporting requirements will be needed to compare treatment performance across institutions.

Third, patient expectations must be managed carefully. Individuals with serious or incurable diseases may interpret regulatory review as proof of established efficacy. Informed consent should therefore clearly communicate the maturity of the evidence, potential benefits, known and unknown risks, alternatives, financial obligations, and available compensation or follow-up arrangements [3].

Fourth, rapid technological development will continue to challenge existing classifications. Gene editing induced pluripotent stem-cell-derived therapies, decentralized manufacturing, automated cell-processing systems, and personalized products may not fit neatly within traditional distinctions between a medical procedure and a manufactured medicinal product [2,6].

Finally, international regulatory convergence remains important. Common terminology, manufacturing standards, long-term follow-up expectations, and evidence requirements could facilitate multinational trials and reduce duplication while maintaining patient protection [2,4,6].

Conclusion

South Korea has created an integrated regulatory architecture that recognizes the distinctive characteristics of cell and gene therapies while separating institution-based regenerative medicine from commercial medicinal-product development. The framework implemented in 2020 established risk-based clinical-research review, institutional qualification, expedited product-development mechanisms, and long-term safety monitoring.

The introduction of advanced regenerative medicine treatment in February 2025 represents an important expansion of this system. It provides a regulated route for selected interventions to be delivered outside clinical research, but it does not replace medicinal-product authorization or permit unrestricted clinical use of unproven CGTs.

The strength of the Korean model lies in its attempt to connect innovation, patient access, product regulation, and long-term safety within a coordinated framework. Its future credibility will depend on consistent evidence standards, clear separation of research, treatment, and commercialization, transparent patient communication, effective post-treatment surveillance, and careful evaluation of outcomes generated under the new treatment pathway.

References

• Kim DS, Bae S. Impact and challenges of enactment for advanced regenerative medicine in South Korea. Front Bioeng Biotechnol. 2022;10:972865. doi:10.3389/fbioe.2022.972865.
• Yoon J, Lee S, Kim MJ, Kim JH. Brief summary of the regulatory frameworks of regenerative medicine therapies. Front Pharmacol. 2025;15:1486812. doi:10.3389/fphar.2024.1486812.
• Yoon J, Lee S, Kim JH. New legal category of “advanced regenerative medicine treatment” in Korea’s amended regenerative medicine law: comparative lessons from Japan. Stem Cell Reports. 2026;21(4):102852. doi:10.1016/j.stemcr.2026.102852.
• Lee S, Lee JH. Cell and gene therapy regulatory, pricing, and reimbursement framework: with a focus on South Korea and the EU. Front Public Health. 2023;11:1109873. doi:10.3389/fpubh.2023.1109873.
• Cai Y, Sui L, Wang J, Qian W, Peng Y, Gong L, et al. Post-marketing surveillance framework of cell and gene therapy products in the European Union, the United States, Japan, South Korea and China: a comparative study. BMC Med. 2024;22(1):421. doi:10.1186/s12916-024-03637-z.
• Song SJ, Nam Y, Rim YA, Ju JH, Sohn Y. Comparative analysis of regulations and studies on stem cell therapies: focusing on induced pluripotent stem cell-based treatments. Stem Cell Res Ther. 2024;15(1):447. doi:10.1186/s13287-024-04065-9.