Part 2: Unexpected innovation and solutions brought on by the pandemic
Rupa Pike, PhD, Sr. Director of Technical Affairs- Advanced Therapies, Thermo Fisher Scientific
This is the second blog in a two-part series that will explore the impact of the COVID-19 pandemic on cell and gene therapy development and how to apply lessons learned throughout the pandemic to enhance process workflows.
Cell and gene therapy (CGT) programs have faced a number of supply chain and personnel obstacles since the pandemic began. Although the full impact of COVID-19 pandemic on research and development is still unclear, there have been some surprisingly advantageous learnings over the past two years. The many sources of functional disruptions during the pandemic have led to an increased focus on optimizing cell and gene therapy manufacturing operations that leverage automation to make production processes more efficient and less prone to manual error.
There is also a renewed interest in improving the robustness of diversified supply chains to maintain reliable access to key raw materials. Given the urgent need to approve new COVID-19 vaccines and therapeutics, regulatory agencies have quickly adapted to streamline the review and approval processes. All these advancements are expected to have a positive impact on clinical and commercial success of future therapies.
Cell and gene therapy manufacturing automation maximizes safety and efficiency
There has been a concerted effort towards automating manufacturing workflows for some time, but the need to work as safely and efficiently as possible during the pandemic enhanced this focus and accelerated implementation. Cell and gene therapy manufacturers are embracing and optimizing automated systems to meet diverse manufacturing needs and accelerate the success of these therapies without compromising quality and efficacy. (1)
With a reduced need for labor-intensive manufacturing, automated systems make it easier to keep production lines up and running with fewer people onsite. This capability is especially critical when pandemic-related mitigation strategies, such as social distancing and building capacity limits, are in place.
The use of fully closed and automated manufacturing platforms offers significant advantages in terms of maintaining consistently high product quality. Fewer manual steps and touchpoints helps reduce the risk of human error, helps drive standardization, and helps prevent contamination. By offering real time process insight and control, automation helps manufacturers respond to alarms, alerts and equipment failure quickly and develop a more in-depth understanding of deviations. When addressing these issues to improve process limitations, digital control systems offer the ability to precisely fine-tune key metrics and parameters. Together, these added capabilities will
Related Resource: Learn how closed system automation for cell therapy can decrease overall costs.
Building robust supply chains for cell and gene therapies
When the life sciences industry rapidly reallocated resources to support COVID-19 treatment efforts, bottlenecks and the inability to access key materials brought many cell and gene therapy programs to a halt. The need for optimization in this space existed long before the pandemic. Supply chain challenges faced during the pandemic highlighted the weakness in supply chain links – and forced suppliers to adapt by designing new strategies to cope with the strain and increased demand.
The pandemic taught many therapy developers that resilient supply chains require transparency and an in-depth understanding of both the quality and availability of raw materials. Since the space has such strict product standards, research laboratories and manufacturers have recognized the need to work with reliable suppliers who maintain rigorous product specifications, have extensive regulatory experience, and can provide real-time information about inventory and lead times to keep programs moving forward. Since the onset of the pandemic, digitalization has been helpful, as manufacturers move toward more efficient virtual audits for vendor qualification and cloud-based systems improve demand forecasting and management of critical material stock.
Related Resource: Vendor qualification process guide
To build robust supply chains that can withstand unexpected and disruptive events, developers are now more readily pursuing dual-vendor sourcing to maintain relationships with multiple suppliers for key raw materials. Extensive border closures during the pandemic also fueled motivation to work with local suppliers, eliminating the risk of being unable to receive essential supplies due to travel restrictions. A digital twin, which is a virtual supply chain replica that simulates the supply chain and can monitor chain of custody and chain of identity and allow for dynamic planning and physical flow of raw materials. can play a significant role in the success of a complex supply chain process. (2)
Streamlining regulatory processes expedites critical approvals
In response to the public health crisis, regulatory agencies modified their processes to conduct swift reviews and approvals of COVID-19 related therapies. For example, while regulatory bodies continue to ensure patient safety through inspections, many have adapted to accommodate remote product or process reviews which can happen more quickly than in-person, onsite audits.
The increased adoption of automated systems is also contributing to increased regulatory efficiencies, as streamlined workflows, improved process oversight, and the reliable delivery of high-quality therapeutics support good manufacturing practice (GMP) compliance. Digitalization can streamline GMP record-keeping process and quality oversight functions. Through large data management and remote access, it can offer superior traceability of all manufacturing steps to improve deviation management.
The faster overall pace embraced by regulatory agencies during the pandemic along with the increased use of systems that promote compliance could potentially transition into more efficient review and approval operations in the long term across multiple therapeutic applications. Since therapies are often developed for populations with otherwise limited therapeutic options, more efficient review and approval processes could lead to earlier initiation of treatment for very sick patients.
Developing cell and gene therapies in a post-pandemic world
COVID-19 pandemic highlighted a spectrum of existing obstacles in cell and gene therapy manufacturing, but also showcased how quickly the industry can adapt to overcome unprecedented challenges and implement improvements as needed. Researchers, developers and industry leaders are collaborating more strongly than ever before, to develop innovative and cutting-edge solutions. The result of these efforts and the lessons learned are set to pave the way for a new era of government-industry partnership, streamlined regulatory reviews, maximized manufacturing efficiency, superior information sharing and robust supply chains. When the pandemic-related disruptions stabilize, this progress will help promote clinical and commercial success in the exciting and promising cell and gene therapy space.
References:
1. Moutsatsou P, Ochs J, Schmitt RH, Hewitt CJ, Hanga MP. Automation in cell and gene therapy manufacturing: from past to future. Biotechnol Lett. 2019;41(11):1245-1253. doi:10.1007/s10529-019-02732-z
2. C. Reed, “The Need For Digital Networks To Support Cell And Gene Therapies,” Cell & Gene, Dec. 30, 2019.