ACTRIS secures GMP status, ready to provide home grown novel treatments to patients

Meet the incredible teams who orchestrated ACTRIS’ journey to operational readiness and how they navigated hoops and hurdles of SOPs, policies and protocols to launch toward success.

We speak with key leads from ACTRIS’ various departments where mutual trust in one another’s expertise was evident in this feat.

Mr Samuel Yang, Head of Quality, Ms June Chia, Head of Lab & Production, Ms Wong Silk Yean, Head of General Operations and Dr Sudipto Bari, Head, Translational Services and Regulatory Management (TSRM), who recount the preparations and concerted effort that made this milestone possible.

A facility to manufacture CAR-T therapies in the face of rising cancer incidence

In Singapore, it is expected that 1 in 4 Singaporeans will be diagnosed with cancer by the age of 75. Cell, tissue and gene therapy (CGT) has come to the fore as possible treatment options for certain forms of blood cancer. Advances in CGT research have now opened up new ways to treat cancer with cells, dubbed as “living drugs”. 

One such class of products available locally is the chimeric antigen receptor (CAR) T-cell that uses patients’ immune cells to target specific cancer cells. Patients who are undergoing CAR-T therapy would first have their immune cells collected in hospitals; these live cells would then be transported to a GMP-compliant facility where it undergoes various stages of processing. 

ACTRIS, which was officially launched in August 2023, is the largest facility alongside several smaller CGT manufacturing facilities available in Singapore prior. For many of the lab officers and staff in ACTRIS, this would be their first full-scale GMP inspection for a 1,450 sqm CGT facility, a significant career milestone indeed.

The road to becoming fully operational

Following the launch, ACTRIS needed two critical green lights before it could be considered fully operational: a Manufacturer’s License to support manufacturing of products to be given to patients under specially authorised clinical use and Good Manufacturing Practice (GMP) certification to supporting manufacturing of investigational products in clinical trials.

Both required rigorous, months-long preparation which culminated in a one-week inspection that pushed the limits of the young ACTRIS team, many of whom joining mid-way on this journey.

This mammoth task pulled together the strength of all four GMP-related departments across ACTRIS.

“We assembled a taskforce led by Dr Francesca Lim, who was the first and then Chief Medical Officer of ACTRIS, to lay the groundwork, identify potential gaps, and work on closing them to mitigate costly errors,” Mr Samuel Yang, Head of Quality said.

Comprising leads from Quality, Lab & Production (L&P), General Operations (Gen Ops) and Translational Services and Regulatory Management (TSRM), the taskforce met twice weekly for months to outline project plans.

Among them was Ms Wong Silk Yean, Head of Gen Ops, whose team had been deeply involved since the facility’s construction back in 2022. Their familiarity with the layout and operations proved invaluable as they quickly briefed and brought new joiners up to speed.

“Under the Gen Ops department, our Facility & Logistics team pre-emptively identified potential gaps and ensured every piece of documentation was ready for the assessors. It was a lot of groundwork, but it laid the foundation for everything that came after,” Silk Yean said.

Building firm foundations through solid workflows and maintaining the clean suites

In line with the Health Sciences Authority (HSA) guidelines for GMP manufacturing of CGT products, the team had to provide a comprehensively designed and well-implemented Quality System that not only complied with GMP standards but also incorporated risk management protocols, that had to be well documented in written Standard Operating Procedures (SOPs). 

Just like a risk-assessment exercise, preparing for the inspection also meant producing a fully mapped out Corrective and Preventive Action plan, leaving no stone unturned. 

While the team could draw on their previous experiences, the reality of operating in a brand new facility brought with it a fresh slate, and most workflows had to be created from scratch.

“On average, this would usually take a year to a year and a half. But we had to expedite the entire effort to six months,” Silk Yean said.

Each SOP required an in-depth understanding of the GMP guidelines, performing GAP assessments and rounds of rigorous reviews before the Quality department could approve them. It was an arm-in-arm effort across the board. 

Against all odds, the team developed an original set of workflows in that time frame. 

Together with the Quality department, by the end of 2024, ACTRIS had prepared a total of 221 SOPs and 487 GMP documents. 

The L&P department also had their hands full with maintaining the clean suites and ensuring all equipment and air-handling systems were properly qualified and ready for use – it was a tedious task, given the sheer volume of equipment under their care. As with celebrating small wins, the team first focused to get two clean suites operationally ready for product introduction during the inspection, and thereafter, continually tweak their approach till the official inspection in September 2024.

“It was an extremely stressful and jam-packed time, and we were heartened by the welfare support from the administrative team who ordered in catered meals, these gestures lifted our spirits and reminded us that we were not alone,” Silk Yean said.

Staying a step ahead with no room for error

As the months whittled down and the inspection dates loomed closer, the taskforce ramped up its preparations, running several dry runs on a weekly basis to fine-tune every documented process. Each session was an opportunity to rectify, put in stop-gap measures and improve, tweak presentation flows, and sharpen the team’s coordinated response strategy. Scribes were appointed as ‘eyes and ears’ at every station to ensure every detail could contribute to learning points and ensure seamless communication during simulations.

“The capabilities of the clean suites ensure that CAR-T cells, which are live cells are transported to a GMP-compliant facility, where it undergoes various stages of processing. Hence, to put it simply, there is no room for error, both on the equipment front and staff protocol front,” Samuel said.

Team insights: ‘Gemba’ may be the alternative ‘G’ in GMP

Ms June Chia, Head of L&P, recounts the many dry runs with professional experienced GMP practitioners from the ecosystem. These dry runs involved “Gemba walks”. She cites a phrase that is often used in manufacturing: go to the Gemba.  It is a concept rooted in the Japanese philosophy of going to the ‘real place’ to truly understand what happens on the ground — a tool that uses thorough walkthroughs to observe and re-learn processes to bridge gaps between theory and application.

During the actual inspection of the facility, equipment and utilities, the mock audits proved valuable in preparing the team to be quick on their feet and answer quick-fire questions posed by the internal inspectors.

“We developed what was called storyboard, to develop answers for anticipated queries, just like how candidates prepare for an exam,” June shared.

With these storyboards and early preparation, the team would “already be few steps ahead with visual mind maps” to present the protocols in place to ensure compliance.

“For the Logistics team, the storyboards ensured we were clear on the SOPs and day-to-day workflows,” Silk Yean added.

With practice and rigorous testing, the team gained confidence that the Gemba method would see them through.

Perfectly attuned with one other

“On inspection day, we functioned like an orchestra performing a well-rehearsed symphony,” Samuel said. By then, every cue, every note had been practised, refined, and timed to perfection.

The Logistics and Warehouse Gen Ops teams were the first to be audited.

From there, the baton passed smoothly to the lab officers, where together with the cell specialists, they performed demonstrations for handling live cell cultures without a hitch. The lab officers explained their workflow with clarity, emphasising how measures were in place to prevent cross-contamination of living cells.

Developing cell therapies at scale

Live cell handling and processing plays a critical role in developing cell therapies but scaling it for GMP manufacturing to achieve clinical dosage poses complex challenges, such as incorporation of automation and ensuring cell viability in maintained consistently in the bioreactors.

"It was satisfying to see all stakeholders and staff coming together, showing confidence and knowledge beyond their areas of responsibility."  

“In-depth questions which would usually be answered by the Quality department, were fielded confidently by our lab officers,” Samuel added.

Months of preparation came together in perfect harmony

After the week-long inspection, ACTRIS worked on addressing the concerns raised by the inspection team and proposed measures for mitigation. On 27 February 2025, ACTRIS was officially granted the Manufacturer's License from HSA, along with the issuing of the GMP certificate.

The ACTRIS cell therapy facility is now officially licensed to produce life-saving and regenerative therapies for patients in Singapore. Being able to manufacture high-quality cell therapies locally will mean that treatments can reach patients in less time, and they get access to life-saving therapies sooner.

Dr Francesa Lim, former Chief Medical Officer, ACTRIS and Adj A/Prof Danny Soon, former Interim Executive Director and Senior Adviser, ACTRIS, sharing words of encouragement with the team after receiving the GMP certificate.

However, the ACTRIS team is not taking a breather just yet.

“This is only the beginning. Moving forward, we will continue to engage with the ecosystem to demonstrate ACTRIS’ capabilities in supporting our healthcare system and patients,” Adj A/Prof Yap Eng Soo, current Chief Medical Officer of ACTRIS since 1 March 2025, said.

With the facility now fully licensed, “ACTRIS is ready to serve the needs of the ecosystem. We have begun triaging the steady stream of business opportunities on the horizon,” said Dr Sudipto Bari, Head of TSRM.

Setting the score for the road ahead

Samuel shared the immense pride he felt was not just from successfully passing the inspection but to see those “who were facing their first inspection at ACTRIS, step up despite the heavy responsibility.”

“Initially, everyone was just working in silos. However, as the months passed, you start to see everyone working together and cheering each other on. The audit was a testament to what we can do as a team,” June said.

“Despite our different backgrounds and expertise, we were driven by the same mission to attain the certification and license to serve our local patient population,” Silk Yean added.

As the team turns its focus to what lies ahead, A/Prof Aloysius Ho, Executive Director, ACTRIS since 1 March 2025, reflected on the people who made it possible, “The team’s dedication to getting this centre operationally ready was evident. With the right infrastructure, talent and systems, it reflects a shared commitment to advancing healthcare and enabling access to therapies for those who need it most. I’m excited for what we’ll continue to build together.”

Kudos to the team that led ACTRIS to secure its GMP status, a memorable feat!