The journey of SS 656 — Singapore’s first national standard for miRNA-based diagnostics—is a showcase in ecosystem synergy. It represents a seamless “bench-to-bedside” transition driven by three core organisations, using the development of GASTROClear as the definitive roadmap.
Early Conception
Bridging the Gap in RNA Diagnostics
Until 2019, the development of RNA-driven molecular diagnostics lacked clear guidelines that could address technical gaps in pre-analytical variability and analytical inconsistencies. This created clinical risks of patient misclassification and screening errors.
SS 656 was developed as a direct response to this gap, by providing clear definition of clinical context, intended use, indications, and limitations before biomarker discovery, providing explicit guidance on controlling pre-analytical variables and formalising analytical validation for miRNA assays.
This collective effort united government agencies, academic institutions, and industry leaders. By drawing on the specialised expertise of the Health Sciences Authority (HSA), Diagnostics Development Hub (DxD Hub), and the NUS Yong Loo Lin School of Medicine, the group established the technical and quality benchmarks essential for facilitating regulatory approvals and expanding global market access. Despite significant logistical challenges posed by the COVID-19 pandemic in early 2020, the Working Group, supported by Enterprise Singapore and the Singapore Manufacturing Federation, launched SS 656 in a record time of one year — compared to the typical standards development timeline of one and a half to two years.
To ensure global competitiveness, SS 656 was carefully aligned with Global Harmonization Task Force (GHTF) and International Medical Device Regulators Forum (IMDRF) guidelines, providing a strong regulatory foundation for Singapore-developed diagnostics to meet international expectations.
The foundation of Singapore’s miRNA leadership was laid at the Yong Loo Lin School of Medicine in the National University of Singapore (NUS). Through their non-coding RNA (ncRNA) Core Facility, the university ensures that early-stage research is “regulatory-ready” from the first day.
- Protocol Implementation: The facility integrates sample collection and processing protocols from SS 656 directly into its early-phase biomarker discovery projects. This ensures that initial research data remains valid as the technology progresses toward clinical use.
- Knowledge Dissemination: In 2022, they published an open-access review article summarising the key principles of SS 656, extending critical knowledge across the global research community. The article has been cited more than 30 times, effectively exporting Singapore’s technical standards to the global research community.
The early adoption of SS 656 has benefited the core facility by providing a strategic differentiator that signals reliability to clinical collaborators and regulators. This standard has enabled the facility and its partners to adopt consistent sample collection and processing protocols within early-phase miRNA biomarker discovery projects. By establishing these rigorous benchmarks, SS 656 ensures that research outcomes are robust and positioned for seamless transition into clinical application, thereby increasing the credibility and international standing of the facility.
The Triple-Helix Engine
NUSMed ncRNA Core Facility: The Discovery Engine
“Early adoption of recognized frameworks, such as SS 656, signals reliability to clinical partners and regulators, and helps to build credibility that differentiates our core facility from other competitors.” — Dr Cheong Jit Kong, Director of ncRNA Core Facility (left)
The Triple-Helix Engine
DxD Hub: The Translation Engine
“DxD Hub’s mission is to take early-stage discoveries and turn them into ISO 13485 compliant, regulator-ready products. SS 656 essentially maps out what that journey should look like for miRNA diagnostics.” — Dr Weng Ruifen, CEO of DxD Hub (left) and Dr Dominic Phua, Principal Scientist of DxD Hub (right)
Bridging the gap between laboratory discovery and a clinical product, Diagnostics Development Hub (DxD Hub) at A*STAR functions as the primary translational platform, taking early-stage discoveries and turning them into regulatory-compliant and ready products.
SS 656 directly supports DxD Hub’s productisation principles through several key mechanisms:
- Upstream Alignment: SS 656 prevents “biomarker in search of a question” initiatives by mandating developers to define clinical needs and intended use from the outset, fostering critical alignment with realistic diagnostic decision points and risk-benefit trade-offs.
- Structured Path and Evidence Integration: SS 656 establishes a clear pathway from discovery through validation and aligns closely with international standardisation concepts. This simplifies the document and presentation of evidence, and enables DxD Hub to seamlessly construct regulatory dossiers without reinventing the structure for each new assay.
In practice, benchmarking incoming miRNA signatures against SS 656 allows DxD Hub to rapidly identify gaps and design development programmes that moves efficiently from prototype to Class C IVD kit.
As the commercial lead and a commercial entity originating from NUS, Mirxes applied the principles of SS 656 to achieve international regulatory success.
An early-stage success story of SS 656 can be seen through GASTROClear, which was co-developed through a major public-private partnership between Mirxes and DxD Hub, along with several other key clinical and research institutions in Singapore. GASTROClear was the world’s first miRNA-based test for early gastric cancer Detection.
Although SS 656 was published in 2020, Mirxes had already integrated its core principles into GASTROClear’s development in 2019. SS 656’s alignment with International and HSA Medical Device Regulatory guidance helped to produce the robust data necessary to secure regulatory confidence and approval from Singapore’s Health Sciences Authority (HSA) for in-vitro diagnostic applications.
Leveraging its success in regulatory compliance and the standard’s alignment with international GHTF and IMDRF guidelines, Mirxes recently achieved a major milestone: in 2025, GASTROClear received regulatory approval from China’s National Medical Products Administration (NMPA) to be registered as an in vitro diagnostic (IVD) product. SS 656 formed the technical foundation for this successful application, opening GASTROClear to a market of over 500 million high-risk individuals.
The Triple-Helix Engine
Mirxes: The Industrial & Commercialisation Engine
“We believe these embedded practices produced the robust data that facilitated regulatory confidence and subsequent approval by Singapore’s Health Sciences Authority (HSA).” — Mr Jeremy Lim, Mirxes
SS 656 is anticipated to become a cornerstone for miRNA diagnostic innovation, with its potential impact extending well beyond current users. The standard is viewed as a strategic asset that positions local organisations to compete effectively on the global stage by demonstrating consistent quality and safety.
The anticipated ecosystem for SS 656 adoption includes:
- Clinical Laboratories: Laboratories accredited under the Singapore Laboratory Accreditation Scheme (SAC-SINGLAS) that are performing Laboratory-Developed Tests (LDTs) for circulating miRNAs are expected to adopt the standard to meet technical competency and regulatory requirements.
- Point-of-Care Innovation: Developers of point-of-care testing (POCT) devices are expected to follow suit, potentially scaling the deployment of miRNA diagnostics to primary care clinics and home settings.
- Training Programmes: DxD Hub envisions leveraging SS 656 as and educational framework for training programmes, such as the Executive Certificate in Product Development and Manufacturing of In-Vitro Diagnostics (IVD) and Software as a Medical Device (SaMD) jointly offered by the DukeNUS Centre of Regulatory Excellence (CoRE) and DxD Hub.
- National, Regional & International Programs:
- National RNA research programs like National Initiative for RNA Biology and Its Applications (NIRBA) and Nucleic Acid Therapeutics Initiative (NATi) are expected to benefit from the standard.
- Within the ASEAN Diagnostics Initiative (ASEAN-DXI), SS 656 can be utilised as a practical technical template for miRNA-based molecular diagnostics, or even as a general guide for molecular diagnostics development.
- Furthermore, the standard has gained international traction, having been introduced to a UK-based developer of livestock diagnostics (MI:RNA Diagnostics) and the Thailand Institute of Scientific and Technological Research (TISTR).
As Singapore takes bold steps forward in healthcare diagnostics, the adoption of SS 656 enables the future of precision healthcare. By ensuring optimised pre-analytical sample handling and reliable analytics, the standard supports the delivery of clinically actionable results, integral to early disease detection.
Moving Forward
Global Relevance and Future Adoption
YOUR STANDARD COULD BE NEXT
SS 656 demonstrates how industry-led standardisation can profoundly benefit the ecosystem. If you have identified a gap in existing standards—whether in healthcare, manufacturing, sustainability, or emerging technologies—we want to hear from you. Proposing a Singapore Standard can help your industry establish consistent practices, support regulatory frameworks, and build international credibility.
Published on 20 Mar 2026