In an exclusive interview with BioPharma APAC, Raman Rao, the Chief Executive Officer of Hilleman Laboratories Singapore, delves into the transformative capabilities of the ACES cGMP facility and the strategic initiatives aimed at advancing global public health. With a focus on the unique position of Hilleman Laboratories as the only multi-modality vaccine and biologics development organization in Singapore, Rao sheds light on the agile manufacturing practices that enable rapid response to future pandemics and the collaborations fostering technology transfer in low- and middle-income countries. Join us as we uncover the innovative approaches driving Hilleman Laboratories' commitment to preventing outbreaks and strengthening healthcare resilience globally.

Can you provide more details about the ACES cGMP facility and its capabilities in terms of vaccine and biologics development and manufacturing?

• The ACES cGMP facility is a 30,000 square foot manufacturing facility which primarily focuses on early clinical development of vaccines and biologics., 
• The facility supplies clinical trial materials for development of up to the Phase II stage and has the built-in capability to pivot to producing vaccines and biologics for Singapore’s use during future pandemics and public health emergencies.
• The ACES facility also works in tandem with the research and development (R&D) laboratory in Biopolis to provide comprehensive end-to-end biopharmaceutical product development solutions, from concept to the pilot manufacturing of clinical trial materials (CTM) for phase I and II clinical studies.
• Through the ACES facility, Hilleman Laboratories can supply scale-up batches and clinical trial materials to local and global research and development (R&D) partners to facilitate early phase clinical development of new and cost-effective vaccines and biologics. 

Capabilities in terms of vaccine and biologics development and manufacturing

• The ACES platform revolutionizes pharmaceutical manufacturing with transformative flexible manufacturing, featuring portable, skid-mounted single-use systems for modular, reconfigurable drug substance (DS) production. Integrated upstream and downstream processes optimize facility use for continuous processing, enhancing speed and efficiency. 
• Concurrent Multiproduct Production is enabled by functionally closed operations in dedicated cleanrooms, preventing cross-contamination.
• On-the-floor real-time analytical testing and Process Analytical Testing (PAT) utilize advanced technology for rapid decision-making, minimizing sample transport. End-to-end production capabilities integrate platform-agnostic DS suites and a pilot-scale fill-and-finish drug product (DP) suite. Manufacturing support infrastructure includes media preparation, equipment staging, warehousing, quality control labs, and utilities holding areas.
• A key highlight of ACES is that it can pivot to manufacturing vaccines for Singapore in the event of a pandemic. The facility is designed to enable production to be agile and easily adaptable for future or emergency needs, which means it could pivot to produce new vaccines to fight the next pandemic without disrupting ongoing operations. 

How does Hilleman Laboratories plan to leverage the facility to advance global public health and address infectious diseases with unmet medical needs?

• The ACES cGMP facility and the R&D laboratory at Biopolis form a vaccines and biologics development and manufacturing hub capable of producing biological starting materials (BSM) and clinical trial materials (CTM) – from early discovery through pilot manufacturing – to deliver global health impact (especially in low- and middle-income countries (LMICs)) and for Singapore’s strategic healthcare needs and pandemic preparedness.
• Facilitating quick access to important CTM, particularly in development of vaccines and biologics as part of clinical trial studies, will elevate Singapore’s role in addressing global health needs and enhance the country’s responsiveness to emerging epidemic and pandemic emergencies. 
• Through expanded global strategic partnerships with LMICs, the ACES facility can hasten the development and scalability of new, cost-effective vaccines and biologics for early phase clinical development, and create more opportunities for technology transfers to larger manufacturers.
• Consequently, high-value, life-saving vaccines and biologics can be made more affordable and widely accessible, especially to people living in LMICs.

Could you elaborate on the significance of Hilleman Laboratories being the only multi-modality vaccine and biologics development and manufacturing organization in Singapore?

• The cGMP facility complements our R&D facility at Biopolis and together, these two facilities form a vaccine manufacturing and development hub that provides comprehensive end-to-end production capability from concept to pilot manufacturing, which is a first-of-its-kind in Singapore.
• As the only multi-modality vaccine and biologics development and manufacturing organization in Singapore, Hilleman Laboratories is able to respond to the next pandemic quickly as the cGMP facility is designed to enable production to be agile and easily adaptable for future or emergency needs
• To date, Hilleman Laboratories remains the only vaccine R&D and manufacturing organization in Singapore capable of developing both drug substance and drug product (to fill and finish) and is well-poised to share our expertise in vaccine and biologics manufacturing to foster local capabilities while bolstering Singapore's resilience against disease outbreaks, especially those with a pandemic possibility. 
• The opening of our ACES facility will certainly provide us with more opportunities to collaborate with stakeholders both with and outside Singapore to drive growth and innovation within the vaccine R&D sector.
  
  

The facility is designed for agile manufacturing. How will this agility help in responding to future pandemics and public health emergencies?

• The ACES cGMP facility is designed to achieve agile manufacturing, through a highly compact and configurable design, with end-to-end production capabilities. Portable, skid-mounted, single-use systems allow the facility’s manufacturing model to remain platform-agnostic and product-independent, thus enabling production to remain agile and easily adaptable for future or emergency needs without significant disruption to ongoing operations. 
• As the facility is designed to be modular and nimble, Hilleman Laboratories is able to pivot its manufacturing quickly during times of crisis, such as switching from regular pilot-scale manufacturing of CTM to the production of vaccines for emergency use in Singapore should such a need arise. Such setup enables the ACES facility to respond rapidly to emerging public health threats, especially at the onset of a pandemic.

Can you discuss the collaborations and partnerships that Hilleman Laboratories has in place to facilitate early phase clinical development and technology transfers, especially in low- and middle-income countries?

• Hilleman Laboratories has established strategic partnerships with the Developing Countries Manufacturers Network (DCVMN), International Vaccine Institute (IVI) and vaccine organizations in South Korea as well as several African countries for technology transfers, clinical trial networks, translational research and training initiatives. 
• For instance, Hilleman Laboratories has rolled out workforce initiatives in Africa in the form of industry partnerships and internship programs focused on vaccine manufacturing to strengthen manufacturing capacity in the continent. 
• Partnerships with regional and global organizations such as the Developing Countries Vaccine Manufacturers Network (DCVMN) to conduct training programs that upskill vaccine manufacturers in low-and-middle-income countries to facilitate technology transfer, so that populations in LMICs have access to vaccines for even the most fatal diseases. Many organizations globally are seeking a trusted and reliable partner for GMP manufacturing of Phase I and II clinical trial materials. With the opening of our ACES facility, Hilleman Laboratories is well-poised to play that role has been in discussion for global partnerships with various organizations.
  
  

Hilleman Laboratories has invested in advanced vaccine platforms like mRNA and viral vectors. How do you see these platforms contributing to preventing outbreaks, both locally in Singapore and globally?

• Through our investment in these vaccine platforms, Hilleman Laboratories aims to support the development of affordable, high-value vaccines that meet public health needs, especially those in developing regions or LMICs.
• The use of live viral vector platforms enable us to develop thermostable vaccines for viruses such as Ebola that are prevalent in LMICs, with the aim of making the vaccine more affordable and improving access for populations in regions where the disease is prevalent. 
• Locally, Hilleman Laboratories is collaborating with the Agency for Science, Technology and Research (A*STAR) to test if a novel circular ribonucleic acid (circRNA) technology could be used to develop a biologically stable and thermostable RNA vaccine against pathogens with outbreak potential.
• This technology could potentially provide greater flexibility in adapting a vaccine to evolving virus strains, allowing for faster response to an outbreak, as well as stability at regular fridge temperatures of between 2 deg C and 8 deg C.

arcilla.fran@biopharmaapac.com