Written by : Chengxun Su
The essential stay home conversations is a series of webinars curated by BCS to explore how the biomedical community is responding to the COVID-19 pandemic and how they contribute to bringing this public health crisis under control. Diagnostic testing or detecting the virus in patients is a critical step in determining the public health response and controlling the outbreak. Following the successful launch of our first webinar with Dr. Timothy Barkham (TTSH) about the efforts undertaken at the front lines of COVID-19 testing, we were honoured to have Dr. Sidney Yee, CEO of Diagnostics Development (DxD) Hub at A*STAR, Dr. Lihan Zhou, co-founder and CEO of MiRXES, and Dr. Tan Min Han, CEO and Medical Director of Lucence, to share the exciting journey of developing and manufacturing these crucial diagnostic kits. The webinar was moderated by Dr Mayura Wagle, Vice President of BCS.
In brief, Dr Yee shared the experience of translating the R&D efforts by A*STAR into the first “ready-made” hospital laboratory SARS-CoV-2 RT-PCR diagnostic test kit – the Fortitude Kit – followed by Dr Zhou on how MiRXES became engaged to manufacture and supply the Fortitude Kit, and finally Dr Tan on the development of a saliva collection technology which can enable non-invasive testing of COVID-19. The speakers gave their insights on how local biotech/medtech start-ups can build and maintain partnerships with key players in the ecosystem to demonstrate value and propel their business forward.
To date, the Fortitude Kit has been deployed in 13 Singapore hospitals and labs, public and private, and more than 20 countries internationally (picture source)
Dr Yee started by briefly introducing the DxD Hub, which is a national platform led by A*STAR with the aim to accelerate the transformation of IPs (from both public institution and private R&D entities) into clinically validated diagnostic devices that are ready for market adoption. She highlighted acceleration as the key strength of DxD Hub, which was responsible for the speed at which they were able to complete product development and industrialization, and is what makes the difference at the time of crisis.
She then emphasized the importance of building collaborations and networks to serve the purpose of bridging and translation, a core activity of DxD Hub. This was illustrated by how existing partnerships that were forged in the past led to DxD Hub being able to start the collaboration between researchers and clinicians as soon as the COVID-19 virus sequence became widely known. When talking about how the process of optimization, regulatory approval (Health Sciences Authority approval and Conformité Européenne marking) and deployment was completed so quickly over the course of 3-4 weeks, Dr Yee also highlighted the importance of collaboration and joint efforts, and conveyed her appreciation to other departments in A*STAR, as well as the government agencies involved and the ONE Singapore approach that has been taken to combat the pandemic as one united nation.
As a public institution, once DxD Hub has done the optimization, development, and production of the test kit, the next step is to transfer the entire process to the local enterprises to fulfil the goal of mass production and bringing economic outcomes. Dr Yee pointed out that most of the time, the aspect of manufacturing a medical device is overlooked in the process of industrialization. This entails not only the production itself, but also theentire process of supply chain, warehouse, stock, sales and marketing, shipping and ordering.
Next, we heard from Dr Zhou about how MiRXES stepped up to ramp up the production of the Fortitude kit and the challenges they faced during this process. The technology transfer was enabled by the fact that MiRXES already has experience working with A*STAR, A*ccelerate and DxD Hub on licensing, transferring and deploying another PCR-based molecular diagnostics product, GASTROClear – a blood test for early stomach cancer detection. With its experience in PCR-based molecular diagnostics product, MiRXES was therefore in a good position to ramp up the production of Fortitude Kit.
Dr Zhou shared that the technology transfer started on the same afternoon on which the partnership was established. They were able to get the process up and running within a week with successful production of two lots of the kits in the first week, and 100k tests in the second week. Together with DxD Hub, they have gone through 7-8 iterations from the design of the packaging, the kind of tubes to use, the labels and the printout of instruction for use. These efforts were made to ensure the usability of the kit, in addition to its performance so that the kit is highly accurate and user-friendly, whilst at the same time relatively affordable to enable the widespread use of the kit worldwide.
Starting from mid-Feb till date, adequate supply was ensured to fulfil all of Singapore’s needs, which set the record for time taken to bring a diagnostic kit from design to field. This was achieved despite precautionary measures such as additional quality control by DxD Hub were put in place to ensure the quality of the kits. Dr Zhou attributed this unprecedented speed to the seamless communication between MiRXES and DxD Hub, as well as the collective efforts of all parties involved in this process and the ONE Singapore approach behind it. Although they encountered difficulties like disrupted supply chain due to border restrictions, they were able to mitigate the situation eventually. Overall, Dr Zhou noted the journey to be a very rewarding experience that has challenged their capabilities not only in manufacturing, but also other aspects such as technical support, logistics, and regulatory approval. Dr Yee also shared that the Fortitude Kit has recently obtained Emergency Use Authorisation (EUA) by the FDA, which is another testament to the quality of the product.
When asked about how local start-ups can be kept in the know-how about opportunities to apply for licensing rights and help with scale up and distribution in the future, Dr Zhou alluded to the fact that the Singapore government has been highly supportive to local biotech start-ups by enhancing their capabilities including product development, manufacturing, commercialization and collaboration with local Institutes of higher learning (IHLs). The information about new products and technology available for licensing has been very transparent in his experience. His suggestion for local start-ups is to stay connected with community and seek collaboration with them actively. Specific to licensing, he considered the experience with local institutions to be quite pleasant as compared to other countries, as a result of the supportive environment that government has forged. Local start-ups are advised to reach out and speak to the key players to bring their business forward.
Next, Dr Tan spoke to the audience about the motivation behind the development of SAFER-Sample saliva stabilization kit and how Lucence decided to undertake its development when the outbreak started. He briefly introduced Lucence, which is a services company that focuses on supplying ultra-sensitive liquid biopsy tests. As the first company to deploy a testing service covering both virus and cancer-related markers in one blood test, Lucence decided to make use of their existing technology on sample collection for COVID-19 virus detection in saliva, with the aim to achieve non-invasive testing of COVID-19.
The SAFER-Sample medical device helps in keeping viral RNA stable at room temperature for up to one week (Picture source)
The motivation behind this technology is the need for high-quality saliva sample to ensure the accuracy of the subsequent testing, which can be collected in a less invasive manner compared to the widely-deployed nasopharyngeal swabbing. Over the past two months, there has been increasing evidence suggesting that saliva may be an alternative form of sample towards COVID-19 diagnosis, which has been adopted by Hong Kong since February 2020. However, saliva has been known to contain RNase which causes the degradation of viral material at the very point of collection. It is hence crucial to ensure that the samples are immediately chilled and transported under a cold chain, which may be difficult to achieve for long-distance transportation and in resource-limited regions. While active investigation is ongoing to explore the usage of saliva sample as a mainstream strategy for COVID-19 diagnosis, less invasive and mass testing could be made possible by deploying the SAFER-Sample saliva stabilization kit, which has now obtained class A device registration within Singapore and looking at FDA EUA approval for global distribution. Dr Tan also spoke of how Lucence, originally a services company, has decided to take on the role of manufacturer to produce and supply the kit to the region at a low cost.
After a round of discussion on the behind-the-scenes of developing and manufacturing the diagnostic kits, the panellists talked about how it was like for their team to divert resources at full throttle towards addressing COVID-19, and how they have maintained normalcy and kept motivation level high during this challenging period. Dr Zhou mentioned that while their cancer-related work has been impacted at this moment, they haven’t pivoted away from it and hope to carry on with their cancer research and launch new products once the pandemic comes to an end. He also relayed his appreciation to the employees who are on the production line of the Fortitude Kit, who have been working incredibly hard since mid-February, highly motivated by the life-saving nature of the work they are doing.
Dr Yee also shared how things have changed at DxD Hub, with development being suspended for some projects. She gave her perspective on how they have learned to recalibrate some of the projects by allocating more time on activities focused on improving productivity such as setting up the quality management system, which is equally important in the process of industrialization. She shared that she has been working with her team together at the front line, which helped a lot to keep the motivation level high.
Lastly, Dr Tan spoke about how their team has expanded from 50 to 70 employees to ramp up the production capacity during this period, and also how his team was motivated when they received support from the community.
The webinar concluded with final remarks on how the biomedical industry would have changed after the pandemic. Firstly, the need for solutions to enable automation was mentioned, and the need to maintain the speed of developing and deployment of marketable medical solutions was also emphasized. Furthermore, it was recognized how resourceful, innovative and collaborative the local biomedical ecosystem has become to enable the successful development and wide spread use of the diagnostic kits during this crisis. Through combating this pandemic as a united nation, Singapore is more ready to tackle greater challenges. The ecosystem will also continue to evolve and hopefully become more vibrant after the pandemic.
Last but not least, BCS would like to thank our panellists for taking out their valuable time and sharing their experiences and insights with us, we would also like to express our gratitude towards A*STAR, MiRXES and Lucence for supporting us with this event.
By Chengxun Su on behalf of BCS