October 30, 2024
This article originally appeared in AABB News, a benefit of AABB membership. Join AABB today to read the rest of this month’s issue.
Advances in cellular therapies and other biotherapies throughout the past decade have transformed patient care and personalized medicine throughout the world. In August 2017, following 30 years of development, the U.S. Food and Drug Administration (FDA) approved the first ever cell-based gene therapy in the U.S., Kymriah (tisagenlecleucel), to treat B-cell acute lymphoblastic leukemia (ALL) and diff use large B-cell lymphoma (DLBCL) Since then, the FDA has approved six CAR T-cell therapies for the treatment of blood cancers. In 2019, FDA Commissioner Scott Gottlieb, MD; and Peter Marks, MD, PhD, director, Center for Biologics Evaluation and Research, predicted the FDA will approve 10 to 20 cell and gene therapy products every year by 2025.2 At the end of the first quarter of 2023, there were more than 100 different approved gene, cell and RNA therapies worldwide, with more than 3,700 more in clinical and preclinical development.
Additionally, the National Bureau of Economic Research estimates that more than 1 million patients will receive treatment with gene therapies, costing more than $25 billion annually by the end of 2034.4 These transformative therapies have the potential to treat and cure a variety of diseases and genetic disorders, including cancer, autoimmune conditions, beta thalassemia, sickle cell disease and much more. Despite the rapid growth and promising benefits to treat and potentially cure diseases, the biotherapies field continues to face infrastructure challenges that hinder the development and delivery of these therapies to patients in need and limit their access to treatment.
Becky Cap, senior vice president of biotherapies at Vitalant, spoke to AABB News about the barriers to scaling up gene and cell therapy manufacturing and how blood centers can meet the growing demand.
“The infrastructure requirements for apheresis, cryopreservation, manufacturing and the preparation of the final product for delivery are all significantly burdensome,” Cap stated. “The question is: how can we create space to allow the hospitals to focus on delivering patient care and take the burden of prepping a product off of them. This is something blood banks do extremely well. And the community blood banks can help extend that geography.”
Today, cellular therapies are increasingly being produced in centralized manufacturing facilities and shipped to medical centers for administration.5 With fewer than 200 hospitals in the U.S. accredited to administer immune effector cell therapies, blood facilities have become a viable option, as they are well positioned to support these therapies due to their existing infrastructure, trained staff, expertise in handling biological materials and established processes for donor recruitment and product distribution.
Vitalant, for example, is a leading provider of biotherapies for hospital oncology and transplant programs across the U.S. Vitalant biotherapy services include cell therapies that provide hematopoietic progenitor cells (HPCs), support of CAR-T product manufacturing, as well as cord blood services through its accredited cellular therapy and cord blood banks.
“When we started with the first CAR-T products, we had a very sick patient population in the hospital, and the only way to support these patients and our medical partners was by having our Vitalant nurses perform apheresis procedures in hospitals with a therapeutic apheresis program,” Cap said. “We are looking at how to extend our therapeutic apheresis services to assist medical facilities across the country, whether it's augmenting an existing hospital-based program or independent of that.”
As cell therapies move into earlier lines of treatment for solid tumors, freestanding collection sites may see an influx of patients, Cap noted.
“Patients who do not have a debilitating disease profile are more able to come into a fixed donor site and may prefer a collection site closer to where they live. To that end, we want to consider how we can support the hospital and the community closer to where the patient lives and lighten the burden on the patient and their family so that they don't have to travel long distances with a family member who has to take off work just to get their apheresis procedure done,” Cap said. “One hospital that we work with has built a lodging space for families. Collecting a patient in their home community also benefits the hospitals by freeing up resources for other patients. There's a huge benefit there that we can help fill, but it requires a different kind of conversation with the hospitals and clinicians in general.”
Developing and implementing standardized approaches for cell collection is critical to ensure safe, high-quality cell and gene therapies and streamline processes for providers. However, standardization is not an easy task due to the complexity of biological materials, variations in manufacturing processes and regulatory requirements. Bringing stakeholders together early on is key.
“Managing the many ‘similar, but different’ protocols is something that everybody talks about as being a huge challenge. It can and should happen, but it will take the stakeholders – therapeutic developers, academic centers, clinicians, regulatory agencies, and accrediting organizations working together to adopt a standard before a regulatory filing is submitted,” Cap said. “It makes sense to work with people who have licensed products to look at the variability in their procedure. Developers often collect a different total nucleated cell (TNC) count based on the specific cell type but there are certain parameters and nomenclature that could be standardized.”
Ultimately, there is no shortcut for standardizing cell collection. It’s a timely process. “You have to look at every procedure in general. This isn't just about apheresis,” Cap said. “You can't rely on muscle memory in these areas to get it right.”
There are multiple ways of collecting a product, including by total time apheresed, total blood volume processed, or by final target cell concentration. “Instead of being overly prescriptive on how to collect cells, we should be focusing on the target characteristics of the cellular starting material for the next step once it’s ensured that product is coming from a collection provider in good standing with the regulatory and credentialing agencies,” Cap said. “With a few key guard bands in place, a single, approved, and accredited protocol could be used for a variety of collections instead of a separate protocol for each unique CGT cellular starting material. This could harmonize up to 80% of the entire collection process. Ultimately, even the remaining 20% could undergo some degree of standardization by using industry-approved templates such as the recently created AABB-ISCT Joint Biotherapies Quality Agreement Template.”
AABB is committed to working with like-minded organizations to advance biotherapies. AABB partnered with the International Society for Cell and Gene Therapy (ISCT) to form a joint working group to tackle important biotherapy challenges and delivery bottlenecks. Some of the collaborative projects from this partnership include:
• In 2015, the AABB-ISCT WG established a project team to address issues concerning the production and standardization of pooled human platelet lysate (pHPL) based on the increasing need for a non-animal-derived source of cell culture growth supplement to support cellular therapy product development. In 2017, the pHPL project team presented its progress at the AABB and ISCT annual meetings. This project team then prepared a manuscript that summarizes the findings and was published as a joint submission in Transfusion and Cytotherapy.
• The AABB-ISCT Joint Working Group Stability Project Team (SPT) was assigned to roadmap a path toward standardization of cryopreserved hematopoietic stem/progenitor cell (HSPC) stability programs. A survey was prepared by the SPT and distributed to ISCT and AABB members. Eighty-two centers worldwide participated in the survey. The report was published in the March 2022 issue of Transfusion.
• The AABB-ISCT working group formed a team to develop a GTP interpretative tool that associates the GTP regulations with guidance references, considerations and additional resources. The tool was developed by a joint team of industry leaders with expertise in cell- and tissue-based product development and manufacturing and published for public use.
• AABB and ISCT developed the Biotherapy Quality Agreement Template to assist with development of a quality agreement. The template includes suggestions based on regulatory standards for the safety and quality of the product and processes and guidance on quality agreements.
Heather Munoz, MN, RN, CPN, CPHON, QIA, director of apheresis operations at Sana Biotechnology, Inc., shared several key factors for success in cell processing for blood collection facilities. “As blood collection facilities transition to cell processing, addressing variability in cellular starting materials is crucial. Variability among donors and external factors can significantly impact the stability and quality of the processed cells. Strategies must be implemented to accommodate this variability,” Munoz told AABB News. This includes standardizing donor qualification protocols tailored to characterization and regulatory standards, along with established procedures and comprehensive training programs for collection facility staff.
Optimizing cell collections through apheresis best practices, annual training and strong vendor relationships between blood collection facilities and equipment manufacturers is also essential. Munoz added, “Facilities should implement tailored training programs that meet customer-specific requirements and foster collaboration with customers to monitor compliance and performance based on feedback from manufacturing success.”
She also stressed the importance of establishing clear communication channels with internal and external customers through regular meetings and discussions about manufacturing challenges to help mitigate risks related to delays and logistics.
Additionally, scalability should be enhanced by adopting adaptable workflows and staffing models to meet increased demand, along with dedicated scheduling processes to improve accessibility, Munoz pointed out. This includes implementing scalable solutions for managing donor and patient screening and collection volumes.
Munoz also acknowledged that a robust regulatory and quality framework is “vital, ensuring strict adherence to standards, conducting regular audits and engaging with accrediting bodies... to guarantee high-quality products and processes, particularly in understanding requirements from non-U.S. sponsors.” She noted that AABB represents expertise in quality management systems relevant to biotherapies and has a long history of helping professionals in the fi eld navigate new regulations and updates. The Association offers such a quality framework and a variety of programs to support the biotherapies community.
Munoz’s key piece of advice for staff at facilities preparing to begin or increase cell processing efforts is to set clear expectations for the qualification process during the onboarding process and to fully understand customer-specific requests. “Establishing clear communication and flexibility to meet customer needs is essential, especially since many customers utilize multiple collection facilities,” Munoz said. “Focusing on standardization and risk mitigation strategies to reduce variability is crucial, so these facilities should prepare for customer-specific protocols, adhere to regulatory requirements and ensure access to large donor pools to meet scalability demands for successful end drug products.”
Looking ahead, Cap hopes the biotherapies community can overcome logistical and regulatory challenges as more blood centers expand their collection eff orts and enhance their role in biotherapies development.
“It’s a big ask and my nice pipe dream. It will require the participation of clinicians, therapeutic developers and hospital systems because it’s the outcome data that matters,” Cap said. “We’re currently dealing with a relative handful of products, and each product has a fairly small population target. If we don't figure this out now, we won't be able to scale. We're shifting to prevalent diseases, and that's going to create some challenges for the health care system.
“We must get more efficient collections, and it needs to happen closer to the patient’s home,” Cap continued. “We must figure out all these barriers to scaling, including high costs, limited treatment centers and logistical barriers. It's a pretty urgent need for our community.”
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