Part 1: Unforeseen challenges brought on by the pandemic
Rupa Pike, PhD, Sr. Director for Technical Affairs- Advanced Therapies, Thermo Fisher Scientific
This is the first 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.
The COVID-19 pandemic placed unprecedented demand on the biopharmaceutical industry to operate with unwavering flexibility and efficiency. To fulfill increased production needs during the pandemic, much of the available raw materials and manufacturing capacity typically allocated to cell and gene therapy programs were redirected towards development of treatments and vaccines to combat SARS-CoV-2. This shift led to a shortage of resources that profoundly affected the complex processes supporting cell and gene therapy development, ultimately causing a decline in new non-COVID-19 related research and development and magnifying pre-existing manufacturing challenges surrounding standardization and scalability.
Pandemic-related cell and gene therapy delays
Clinical trials for cell and gene therapies faced unexpected obstacles, as COVID-19 cases started surging. Travel restrictions and heightened precautions made it difficult for patients to safely travel to clinics to receive scheduled treatments (1). Both allogeneic and autologous therapies were hindered due to social distancing and quarantine requirements which prevented healthy donors and eligible patients from traveling to the clinic. Many apheresis centers either closed or were reorganized to focus on COVID-19 care (2), restricting the collection of patient or donor starting materials which, in turn, affected both trial operations and material supply. Additionally, cold-chain systems were used to move and manage supplies dedicated to fighting the pandemic, affecting the ability to ship and store cell and gene therapy materials and products.
As hospitals became overwhelmed with COVID-19 patients, there was a lack of available medical personnel and space for monitoring patients for treatment efficacy and side effects. Many medical institutions also paused non-essential services, leading to study delays. In the realm of discovery research, critical lab activities slowed as new measures were put in place to ensure the safety of staff. Similarly, good manufacturing practice (GMP) facilities implemented protocols to isolate operators with extra personal protective equipment (PPE) and distancing barriers. While these mitigation efforts were important in reducing infection risk among workers, the new rules and restrictions prevented facilities from operating efficiently and at full capacity.
Supply chain issues and a lack of essential raw materials
Research and manufacturing of COVID-19 vaccines and treatments led to increased demand for plasmids, cell culture media and other materials essential to cell and gene therapy development. With supply chains strained, developers faced shortages that led to slowing down of some programs or even a temporary shutdown of others.
Advancing cell and gene therapy development post-pandemic
With some approved treatments already commercially available, cell and gene therapies continue to offer tremendous hope for patients facing a spectrum of life-threatening diseases. Although progress in the cell and gene therapy space has been impeded by the COVID-19 pandemic, the disruption has also led biotherapeutics manufacturers to renew their commitment to optimizing both development and production processes to help ensure future clinical and commercial success. COVID-19 has offered developers and industry leaders the opportunity to collaborate on new, innovative solutions that will ultimately advance cell and gene therapies.
References:
1. Qiu, T., Wang, Y., Liang, S., Han, R., & Toumi, M. (2021). The impact of COVID-19 on the cell and gene therapies industry: Disruptions, opportunities, and future prospects. Drug discovery today, 26(10), 2269–2281. https://doi.org/10.1016/j.drudis.2021.04.020
2. M Kulik, J Ochs, N König, R Schmitt. Automation in the context of stem cell production – where are we heading with Industry 4.0? Cell Gene Therapy Insights, 2 (4) (2016), pp. 499-506.