By Luisa Sterkel & Joana Loureiro, Tenthpin Consultants and Dr. Frank Altznauer Chief Industry Advisor at Tenthpin
Despite the now evident impact of cell therapies on the standard treatment of patients suffering from different medical conditions, the progress of cell therapies in development gets hindered by challenges such as regulatory framework gaps, stringent Food and Drug Administration (FDA) requirements, high costs, and limited access to therapies. These aspects underscore the pressing need for collaborative efforts to overcome these barriers and bring innovative treatments to those in need.
Actually, cell therapy trials faced delays in FDA approvals, mainly regarding clinical trial applications (CTA), impacting the progress of innovative treatment methods. A significant development from the FDA took place in March 2023 with the creation of a super unit called the Office of Therapeutic Products (OTP). This resulted from the reorganization of the Center’s Office of Tissues and Advanced Therapies (OTAP) by the Center for Biologics Evaluation and Research (CBER), which oversees the regulation of biological products, ensuring their safety, efficacy, and availability in the United States. The response aimed to manage the increased workload caused by the growing number of Cell and Gene Therapy (CGT) projects in biotech pipelines and the subsequent rise in trial numbers. The specialized OTP unit within CBER has dedicated teams for various products and processes, ensuring expertise and timely interactions with sponsors (See FDA press release).
With the increasing number of CGT projects in pharmaceutical company pipelines, Tenthpin recently published an article delving into the intricacies of the supply chain for these trials. The article, titled “Untangling the Complexities of Cell and Gene Therapy Clinical Trials: A Supply Chain Perspective”, highlights challenges ranging from manufacturing to product delivery. Addressing the demand for an affordable and efficient CGT manufacturing and delivery approach is crucial. Pharma companies grapple with significant delivery challenges, especially for individualized cell therapies, where infrastructure, equipment, and expertise present notable bottlenecks. Outsourcing the production of these therapies to Contract Development and Manufacturing Organizations (CDMO) has proven effective, though businesses should carefully weigh the pros and cons to optimize benefits. Cost implications must be considered diligently to ensure affordability.
How can pharma companies overcome major delivery challenges of cell therapy products? Which approach is believed to be the most effective strategy in terms of accessibility and costs?
Point of Care (PoC) manufacturing emerges as a transformative solution, positioning the manufacturing process close to patients and significantly reducing logistical complexities. On-site production of therapies within hospitals and academic medical centers is specifically tailored for scenarios with limited opportunities for medicine storage or those requiring time-sensitive delivery. By promising shorter lead times from cell harvesting to therapy delivery, PoC manufacturing stands as an ideal solution to overcome challenges associated with the entire journey of autologous cell therapy trials and is particularly well-suited for critical clinical situations.
Despite the evident benefits, life sciences companies express reservations regarding process standards, compliance, cost savings, regulatory approaches, and facility readiness. Nevertheless, the introduction of PoC manufacturing marks a revolutionary paradigm shift, strategically bringing the manufacturing process closer to patients and adeptly addressing logistical challenges. From an end-to-end perspective in clinical trials, this decentralized approach represents a cost-saving measure for trial sponsors. The streamlined logistics steps, in comparison to a centralized manufacturing approach, contribute to cost reduction and accelerate the entire journey. It expedites patient treatment by eliminating the need to ship materials to a centralized production site and then back to the patients.
The traditional centralized model, with its complex logistics involving multiple steps and stakeholders to guarantee the cold chain, track the chain of identity, and maintain the chain of custody for each individual batch, is simplified with PoC manufacturing sites. Additionally, close real-time monitoring of trial progress and patient status, along with reduced dependence on biotech or pharma production slots for treatment scheduling, enables the treatment plan to better align with the clinical readiness of the patient.
Collectively, these factors simplify the scheduling process, reduce waste due to higher chances of delivering the product in the appropriate quality, and improve overall coordination, leading to cost reductions. Undoubtedly, the application of PoC manufacturing in the context of multicenter trials will increase patient access to these studies from multiple locations worldwide.
From a perspective of the hospital, PoC manufacturing also presents an opportunity. It not only allows the streamlined conduct of trials but also enables the establishment of specialized facilities managing independent research. This strategic investment aligns with the broader goal of advancing medical knowledge and innovation, facilitating the development of new therapeutic options, even without the necessity of industry partners.
With the success of these therapeutic modalities, there has been an increase in investment for the investigation and further development of new therapeutic opportunities. As regulatory roadblocks are being addressed and solved, more trials are underway, leading to a heightened demand for clinical finished goods (CFG). Consequently, the existing capacity does not always meet the demand, and biotechs in such scenarios struggle to provide therapies quickly enough for infusion. This not only poses a challenge to supplying the market with approved therapies but also affects the supply for clinical trials, which must ensure delivery during the patient’s clinical readiness window.
Given that some manufacturing units cannot keep up with the demand, this supply inefficiency becomes a motivation for hospitals and healthcare centers to shift towards the PoC manufacturing strategy as an alternative to meet trial and commercial demand.
PoC manufacturing holds significant promise for individualized medicine and faster treatment access, streamlining the vein-to-vein supply chain for autologous therapies by eliminating the need for extensive transportation and complex distribution networks. Examples such as the collaboration between Orgenesis and Johns Hopkins University showcase the potential of PoC facilities (see press release), facilitating efficient transitions from laboratory research to clinical trials.
The successful implementation of PoC requires planning, technology investment, collaboration between pharma and healthcare providers, and adherence to strict quality and regulatory standards. The FDA’s commitment to providing clear guidance on distributed manufacturing and PoC scenarios underscores the industry’s evolution.
A final thought:
In conclusion, this article encourages pharmaceutical and biotechs to strategically address financial and logistical obstacles in cell therapy trials by integrating PoC manufacturing into their global supply chain operating model. Collaborating with and supporting hospitals in adopting and executing this manufacturing approach can enhance its effectiveness.
Pharma companies have been considering to enable global clinical trials and ensure widespread access to cell therapies for everyone through the establishment of semi-centralized facilities worldwide at a regional level. However, this approach would undoubtedly present logistical challenges and financial burdens for biotechs, patients, and insurance providers, requiring a substantial number of resources, networks, and facilities to ensure the final product’s administration. In light of the insights presented in this article, PoC manufacturing appears to be a viable solution encompassing the full spectrum of benefits.
Understanding complexities, proactive problem-solving, and fostering collaborative relationships can unlock cost-saving advantages, making therapies more accessible across social strata. Despite perceived slow progress in PoC as decentralized manufacturing, the increasing investment in cell therapy pipelines underscores the need for a serious consideration of this strategy as the primary option for biotech and pharma companies.
We believe that the impact of PoC manufacturing on the cell therapies supply chain deserves our best attention and investment in a future article to explore whether PoC manufacturing represents the ideal scenario for decentralized clinical trials.
