sia Pacific (AP) is an immensely diverse and dynamic region with varying regulatory capabilities and capacities; consequently, AP regulators and industry are always seeking opportunities to improve the regulatory environment by adopting best practices and leveraging innovative technology to accelerate patient access to new medicines. This spirit of close collaboration and interaction was reflected in the theme of DIA Singapore Annual Meeting 2024: Cultivating Synergies in Clinical Research and the Regulatory Environment to Innovate Healthcare. One thing is clear: AP is moving forward in step with contemporary global trends and innovations in adaptive regulatory frameworks, clinical research, and drug development.

Regulatory System Optimization

With the emergence of new technologies such as artificial intelligence (AI)/machine learning (ML) and new product types like regenerative cell and gene therapies, several AP regulatory authorities are going through a major transformation to rapidly adapt to this evolving environment while safeguarding public health. Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), one of the most stringent regulatory authorities in the region, announced the agency’s New (Fifth) Mid-term targets, with the objectives of actively contributing to promote practical applications of regulatory science; to strengthen the agency’s international capability; and to improve the quality and efficiency of their services. Specifically, PMDA shared news of the establishment of its Centre for Regulatory Consultation of Paediatric and Orphan Drugs; its new notification regarding the Basic Principles for conducting Phase 1 studies in Japanese prior to initiating multiregional clinical trials (MRCTs); and the setup of regional offices in (Bangkok) Thailand and in Washington DC (US).

South Korea’s Ministry of Food and Drug Safety (MFDS) highlighted its recent World Health Organization (WHO) Listed Authority (WLA) designation and introduced the implementation of an enhanced expedited pathway, Global Innovative Products on Fast Track (GIFT). The agency also shared that they co-hosted their first international symposium on the use of AI in medical products with the US Food and Drug Administration (US FDA) in February 2024.

Other AP regulators such as the Indonesian Food and Drug Authority (BPOM) and Thailand FDA shared how their regulatory frameworks are optimized with digitalization, including the issuance of electronic labeling guidance and the initiation of pilot programs. For example, in September 2023, BPOM embarked on a two-year eLabelling pilot program utilizing the GS1 data matrix for serialization purposes, supported by the website and mobile app they developed. Other AP markets provide additional examples of eLabelling implementation.

Accelerating and Streamlining Regulatory Processes for New Product Registration and Post-Approval Changes (PACs) with Regulatory Reliance

Industry associations often contribute recommendations to shape regulatory policy through sharing case studies, such as the experiences in applying regulatory reliance via work-sharing/reliance programs (e.g., Project Orbis and Access Consortium) for new product registration. Application of reliance principles for a post-approval changes (PACs) pilot submission to 48 National Regulatory Authorities (NRAs) resulted in the reduction of global approval timelines and implementation from 2.5 years to 6.5 months. This PAC reliance pilot was facilitated by a cloud-based data and information exchange platform, allowing health authorities’ questions and assessments to be shared among the NRAs.

Reducing country-specific requirements and adopting international standards for effective PACs submission remain important goals for industry and regulators. In this spirit, PMDA, the Australia Therapeutic Goods Administration (TGA), and the Philippines Food and Drug Administration (Ph FDA) shared examples of their respective agencies’ tools to facilitate regulatory reliance, such as publication of English-language assessment reports and adopting flexibility in national provisional/priority review pathways with work-sharing programs to improve regulatory timelines.

Innovation in Clinical Research and New Regulatory Trends

Big data analysis, disruptive innovation, and patient perceptions are increasingly important and imperative in drug development. For research institutions, pharmaceutical companies, and clinical research organizations (CROs), drug development has been revolutionized using circulating tumor cell-derived organoids as tools, better research materials, and biomarkers for assessing drug sensitivities and drug screening.

Research institutions continue the lessons of adapting quickly and applying flexibility learned during the COVID-19 pandemic for conducting clinical trials. This includes the utilization of Real-World Data/Evidence (RWD/E) in drug development in the region; for example, in early asset planning, disease/treatment landscaping as well as protocol optimization. Digital health technologies are being adopted to simplify trial procedures, reduce caregivers’ burden, and facilitate patient recruitment and improve patient diversity in clinical research. US FDA’s guidance provides examples of potential digital health technologies in clinical research.

With artificial intelligence (AI) and machine learning (ML) progressively playing a vital role in healthcare, the Singapore Health Sciences Authority’s (HSA) considerations and perception in regulating AI/ML medical devices include exercising clinical governance and oversight over the adoption and implementation of AI/ML medical devices as well as contingency plans to remove the AI/ML medical devices from the operational workflow where necessary. Industry shares many overlapping perspectives and goals on regulating AI/ML-connected medical devices and related products, such as the implementation of risk management processes; conducting high-quality training, validation, and testing of data from AI; and setting up quality management systems for the regulation of AI/ML products.

Continuous manufacturing (from ICH Q13 below: “the continuous feeding of input materials into, the transformation of in-process materials within, and the concomitant removal of output materials from a manufacturing process”) is another key regulatory trend that enables flexibility in batch size manufacturing, production processes, and formulation adjustments. With the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q13 (Continuous Manufacturing of Drug Substances and Drug Products) guidance finalized in 2022 and subsequently adopted by various health authorities, the need for further engagement and sharing of best practices to drive globally aligned solutions remains.

ICH E6 (R3) Data Governance and Decentralized Clinical Trials in Asia Pacific

In response to the increasing diversity of clinical trial designs and data sources employed to support regulatory and other health policy decisions, the ICH published a reflection on Good Clinical Practice (GCP) Renovation in May 2021. The European Medicines Agency (EMA) has since shared the corresponding progress of the subsequent renovation of the ICH E6 (GCP) guideline; in particular, on how the new guideline provides clarity in the application of quality control to the relevant stages of data handling to ensure clinical trial data quality for reliable results. Computerized systems should also be fit for purpose proportional to their importance to safety and reliability of results.

As more digitalization measures (e.g., electronic consent and remote patient monitoring and data collection) were adopted in clinical trial designs, and as trials are becoming increasingly patient-centric, several regulatory guidance documents on decentralized clinical trials (DCTs) were published in 2023. A presentation summarizing the AP DCT regulatory landscape noted no divergence among US FDA, EMA in the EU, and AP regulatory requirements for DCTs in, for example, Taiwan; the Singapore HSA has also issued guidance on two topics related to digital clinical trials, one in response to the COVID-19 pandemic and another for implementing electronic consent. However, further refinement of such guidance may be required to address local operational challenges.