With great excitement, PDA’s Singapore Chapter opened its March 21 meeting on cell and gene therapy to a wide audience. The meeting coincided with the release of PDA Technical Report No. 81: Cell-Based Therapy Control Strategy. More than 50 individuals across the industry participated, making this the second largest-attended event organized by the chapter.
Chapter president Dinesh Khokal, PhD, kicked things off with a rapid-fire overview of developments in the field of cell and gene therapies. According to Khokal, the U.S. FDA forecasts that approvals of advanced therapy medicinal products (ATMPs) will grow by 900% in 2019! After stunning his audience with that jaw-dropping statistic, he provided some back-to-basics information on the characteristics of cell and gene therapies. For example, these therapies can often be combined with medical devices, forming a combination ATMP to treat patients.
Khokal then moved on to the realities of the current landscape—low commercialization of treatments to date due to the complexity of the products, high developmental costs, low investment returns and difficulties in consistent and reproducible manufacturing. The greatest challenge? Regulatory hurdles. He appealed to the regulators in the room for greater clarity on ATMPs. Khokal concluded that, while these new treatments hold great promise, proceeding slowly will be more prudent to avoid putting patients at risk.
Expounding on Khokal’s update, Singapore regulator Lee Lee Ong, PhD, who specializes in ATMPs, provided more specifics. She reminded the audience of why regulation of this field was necessary, citing early complications and deaths due to these therapies triggering adverse immune system reactions in patients. Additionally, she pointed out that the cells used in these treatments are more complex in size and nature than classic pharmaceutical products primarily composed of an active molecule. Additional risks are linked to donor variability, complex manufacturing and batch-to-batch variation. With autologous manufacturing, i.e., one batch/dose produced, validation becomes a challenge. Ong reinforced that, due to a ATMP’s short shelf life, some QC test results for batch release may not be available until after therapy administration. And, she pointed out, such treatments would remain in the treated individual for a long time, as the product can integrate into the chromosome and be passed down to the next generation.
In spite of these challenges, Ong emphasized the potential of cell and gene therapies. Yet the need to rethink regulatory frameworks for cell and gene therapy applications is real. Although Singapore is considering revising its 1975 Medicines Act, in part, to take into account these new therapies, she acknowledged that the technology is moving much faster than the regulation. Thus, she supports a collaborative effort with industry and regulatory agencies going forward.
Next, Gary Khoo, PhD, offered an industry perspective on manufacturing challenges and opportunities in T-cell therapies. He presented an overview of the current cell and gene therapy landscape and a background on chimeric antigen receptor (CAR) T cell therapy science, highlighting similar challenges raised by Khokal and Ong. Khoo then gave a general overview of CAR-T processing, purification processes and technologies available. Despite its challenges, manufacturing of immunotherapies does present certain opportunities. Due to their highly potent and durable responses, including complete responses for patients who fail standard treatment, CAR-T cell therapies remain a treatment with great potential. The advent of these life-saving therapies would also accelerate acceptance and adoption of new technologies, possibly driving material and QC costs down and, ultimately, making them more accessible to patients.
The final speaker, Richard Chai, wrapped up the event by presenting a succinct review of regulatory guidelines pertaining to contamination control in ATMP manufacturing. He touched on the main sources of microbial contamination in cleanrooms, mitigation strategies and disinfectant selection using real-life examples of biofilm contamination and remediation.
Throughout the session, moderator Wallace Torres, PhD, drew the audience into the discussion. Consequently, the sessions were highly engaging, seasoned with spirited participation and robust discussions between the speakers and the audience.
The chapter thanks the speakers for their participation.
PDA Who's Who
- Richard Chai, Technical Service Manager, STERIS
- Dinesh Khokal, PhD, Director, External Affairs, JAPAC and LatAm, Amgen
- Gary Khoo, PhD, Head of Process Science and Technology, Tessa Therapeutics
- Lee Lee Ong, PhD, Senior Regulatory Specialist, Singapore Health Sciences Authority
- Wallace Torres, PhD, Quality Site Head, Amgen