ICH 산하 세포유전자치료제 논의그룹(Cell & Gene Therapy Discussion Group, CGTDG)이 작성한 전략 문서로, 세포·유전자치료제를 포함한 첨단바이오의약품(ATMP) 분야에서 향후 ICH 차원의 국제 가이드라인 개발 및 개정 방향 등 중장기 규제조화 로드맵을 제시하기 위해 마련되었다.
ATMP는 기존 치료법이 제한적인 질환을 대상으로 질병의 근본 원인을 치료할 수 있는 혁신 의약품으로 빠르게 개발·확산 중이다.
2024년 기준 전 세계적으로 300건 이상의 ATMP 관련 지역별 가이드라인이 존재하고 있으나 국가·지역별 규제 기준의 차이로 인해 글로벌 임상·허가·개발에 구조적 어려움이 있는 현실이다.
현재 ICH 차원의 ATMP 전용 가이드라인은 ICH S12(유전자치료제 비임상 분포) 1건에 불과할 뿐더러 유전체 삽입, 오프타겟 편집, 장기 안전성 등 핵심 이슈는 충분히 다뤄지지 않고 있다.
ATMP는 제조공정과 제품 특성이 밀접하게 연관돼있어 단순히 기존 바이오의약품 규제를 적용하기 어렵다.
CGTDG는 ATMP를 단순유전자치료제, 세포치료제, 조직공학제제, 복합 제제로 구분하고 in vivo / ex vivo 유전자치료, CAR-T 등 다양한 모달리티 포함한 의견을 제시하였다.
CGTDG는 향후 ATMP 규제를 지역별 개별 대응이 아닌, 글로벌 조화 체계로 전환함에 있어, 아래 내용을 권고하였다.
- ATMP 특성을 반영한 신규 ICH 가이드라인 개발 또는 기존 가이드라인 개정 및 부속서(Annex) 추가
- 상세 규정보다 기술 변화에 대응 가능한 높은 수준의 원칙 중심 접근
- ATMP 전주기(개발–허가–시판 후 관리)를 포괄하는 규제 프레임 정립
- 현재 개정 또는 논의 중인 ICH 가이드라인(Q1, Q6, M4Q, E23 등)과의 정합성 확보 강조
INTRODUCTION
The development of advanced therapy medicinal products (ATMPs) has progressed over the past several years, and the field continues to see the emergence of many new therapeutic modalities. ATMPs, which encompass cell and gene therapy (CGT) products, are often transformative medicinal products to treat conditions for which there are limited or no other treatment options or to treat the underlying cause of disease.
The growing global development of ATMPs is reflected in the large number of regional guidelines specific to these products. An analysis conducted by the ICH Cell and Gene Therapy Discussion Group (CGTDG) in December 2024 indicated that more than 300 ATMPspecific guidelines had been issued in draft or final form by ICH members and observers represented in the CGTDG (see Annex II below). This growing number of region-specific guidelines underscores the need for harmonised global regulatory and development approaches.
At this time, there is one finalized ICH guideline dedicated to ATMPs, namely, ICH S12 Nonclinical Biodistribution Considerations for Gene Therapy Products 1 though this does not recommend approaches to testing for genomic integration or off-target editing, which are important for many ATMP products. ATMPs are mentioned in several ICH guidelines (e.g., ICH E2F2; ICH Q5A(R2) (Annex 6)) 3 and are in scope of ongoing revisions of quality guidelines on stability of drug substances and drug products (ICH Q1(R1))4 and specifications (ICH Q6 (R1))5. However, common documentation standards for ATMP quality information are not yet established within the ICH framework, though the updates in the ICH M4Q (R2) revision 6 may address several aspects. In addition, efforts on a new guideline, ICH E23 7 Considerations for the Use of Real-World Evidence (RWE) to Inform Regulatory Decision Making with a focus on Effectiveness of Medicines, will be valuable to the ATMP field.
At this time, the absence of international guidance on many considerations during the life cycle of an ATMP and the lack of harmonisation for ATMP regulatory expectations result in challenges to global drug development and regulatory decision making. The rapid evolution of new technologies in the ATMP field also makes it challenging to establish regulatory expectations, particularly given the emerging new types of ATMP products and manufacturing processes.
There is a wide variety of complexity across ATMPs, and special considerations often depend on the specific ATMP subclass. Notably, many regional guidelines focus on a specific subclass of ATMP products. While nomenclature and classification of ATMPs are not globally aligned, these are typically codified in regional laws and regulations and are out of scope of ICH.
For the purposes of the ICH CGTDG’s work, the WHO framework 8 and associated terminology were applied. Applying the WHO definitions, ATMPs include four subclasses of medicinal products: (1) Gene therapy products, (2) cell therapy products, (3) tissue engineered products, and (4) combined ATMPs, and the WHO definitions of these ATMP subclasses are provided in the Glossary. Gene therapy products include both in vivo products that deliver therapeutic genes or correct genetic mutations directly in the patient cells (e.g., nucleic acid-based or viral vector-based) and ex vivo products where the recombinant gene is delivered to cells outside of the patient’s body. The latter are often called ex vivo genetically modified cells, ex vivo gene therapies, or cell-based gene therapies (e.g., CAR T-cell products).
The nature of these products and their manufacturing processes can require alternative approaches (with scientific justification) from those established for traditional biotechnological and biological products. In addition, the unique considerations often differ between ATMP modalities (e.g., nucleic acid-based ATMPs versus cell-based ATMPs). While the principles of drug development generally apply to ATMPs, existing ICH guidelines are not always directly applicable and fit-for-purpose approaches may be justified. The CGTDG herein provides a strategic roadmap with specific recommendations for new ICH guidelines, revisions, or annexes to existing ICH guidelines to address the special circumstances for ATMPs, while adopting high level principles given their complexity, diversity, and evolving nature. The strategic roadmap is aligned with ongoing revisions of ICH guidelines, which include in their scope consideration for a broad range of ATMP modalities. Neither the recommendations in the strategic roadmap nor the high-level principles are to be understood as scientific guidance but instead may be the basis for future guidelines.
ICH_2025.12.01.
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