here has been a shift from late phase to early phase design and toward novel drug development in Asia Pacific (APAC), with particularly significant growth in China from 2012 to 2021. In 2021, one speaker noted, APAC accounted for approximately 50% of new global trials with an increasing trend of phase 1 to phase 4 trials being conducted in the region.

In Asia, apart from lower labor costs, running trials is less costly than in the US and EU due to tax incentives and government funding. One presenter noted that the cost per subject in many Southeast Asian countries is half of what the US offers. An example of a government-funded initiative to encourage research and clinical trials is the Research, Innovation and Enterprise (RIE) Project that was launched in 2010 in Singapore. In 2020, the Singapore government announced that it will continue to support investments in research, innovation, and enterprise with a budget of S$25 billion for the RIE2025 plan which covers years 2020 to 2025. Under RIE, the NMRC (National Medical Research Council) focuses on strategic R&D investment in three key areas: human capital and talent development programs, knowledge enablers and infrastructure initiatives, and research grants.

APAC also offers the advantage of an evolving regulatory environment where its national governments are working toward strengthening GCP compliance, streamlining regulatory requirements, and accelerating clinical trial application approval processes. This can be seen in various harmonization agreements among countries in APAC and ASEAN, such as the ASEAN Guidelines for Harmonisation of Standards adopted to support the implementation of Mutual Recognition Arrangements and harmonized regulatory regimes between ASEAN Member States, as well as implementation of regionally standardized documentation including the ASEAN Common Technical Documents (CTD) and ASEAN Common Technical Requirements (CTR).

Additionally, some countries within APAC are members of the ARO (Academic Research Organization) Alliance for ASEAN and East Asia (ARISE). ARISE supports its member countries (Thailand, Philippines, Indonesia, Vietnam, and Malaysia) to advance clinical trials, especially multiregional clinical trials (MRCTs) in Asia, by providing support from training to tools that enable effective and efficient clinical trials and contribute to regulatory harmonization in Asia.

Moving forward, innovative clinical trial designs will evolve towards being adaptive: allowing testing multiple drugs on a single disease, a single drug across multiple diseases, and integrating prospective and retrospective data. Furthermore, the global future of clinical trials will increasingly see adoption of artificial intelligence and machine learning from drug selection, site intelligence, patient enrollment and retention, to improving accuracy of data analysis and adverse event monitoring, and this adoption is anticipated to correspondingly increase in APAC.

Cell, Tissue, and Gene Therapy

While advanced therapies are transforming the treatment landscape, they also present unique challenges to developers, such as:

• Small sample size due to the nature of the disease.
• Complex manufacturing and distribution, leading to a shift from a supply chain model to a value chain model due to the uncertainty in vein-to-vein time for autologous CAR-T (e.g., limitations in supply of raw materials, manufacturing slot availability, manufacturing delay/failure).
• Unclear, ambiguous regulatory guidance due to an unharmonized yet rapidly evolving global regulatory framework. Without harmonization, there might be differences across countries in definitions, terminology, classifications, pathways, and data requirements. Furthermore, many countries rely on their guidance for biologics, which may not be fit for this CTGTP purpose. (One example is the inconsistency in GMO requirements for environmental risk assessment, which could lead to potential delay in clinical trial approval timelines.)
• Uncertainty about long-term product safety.
• Lack of resources: From experienced personnel, to limited suppliers for raw materials and other manufacturing-related products, to qualified facilities.

However, there are some positives to these challenges. For example, health authorities and industry, together with multilateral coalitions and initiatives, have opened dialogues towards regulatory convergence to facilitate global development as well as strengthen country capacity to regulate CGT products.

Examples of such collaborations include:

• Guiding principles on how to build a regulatory framework for CTGTP, Considerations in developing a regulatory framework for human cells and tissues and for advanced therapy medicinal products, published by WHO in May 2023
• ICH Harmonized Guideline Nonclinical Biodistribution Considerations for Gene Therapy Products S12, adopted in March 2023
• Position paper on Points to Consider to Promote Convergence and Reliance Approaches for ATMP, published by IFPMA in February 2023.

Lifecycle Management

Malaysia NPRA and Thai FDA have begun their journey toward digitalization and reliance, from accepting electronic documents such as e-CPP and e-GMP to embarking on NPRA e-Labelling pilots. NPRA and Thai FDA have also utilized reliance beyond review of new drug applications into post-approval changes and GMP clearance, respectively. Despite this positive outlook on reliance, there is still work to be done on further acceptance of reliance and building of trust among other national regulatory agencies.

The DIA CoRE Singapore Annual Meeting convened in July 2023 under the theme Asia at the Forefront of the Healthcare Evolution. Among the many topics shared and discussed, three highlights were (1) Clinical Trials in Asia and ASEAN as a hub for clinical trials, (2) cell and gene therapies, and (3) the special ASEAN Townhall.

Disclaimer: The opinions expressed in this article are solely those of the contributors and not necessarily those of Novartis. Novartis does not guarantee the accuracy or reliability of the information provided herein.

The authors thank Louise Watt and Wong Kum Cheun (Novartis Asia Pacific) for their assistance with this article.