The Need For Digital Networks To Support Cell And Gene Therapies

By Carla Reed, president, New Creed LLC

Cell and gene therapies are game changers. Critical health conditions that were once chronic or terminal are now being addressed, which is exciting news for patients and caregivers. But these therapies have a level of complexity from a supply chain perspective that needs new approaches, including a high level of information sharing and integration.

This topic was covered from different perspectives at two conferences I recently attended. What was fascinating was that both events highlighted a key enabler for these personalized therapies — a community-based supply chain supported by a responsive digital network.

Creating The “Digital Twin”

The first of these two events, the Futurelink conference hosted by Tracelink in Nashville, TN, included presentations and case studies from experts in the field of network technologies and tools, the use of orchestration platforms, and the growing value of data available through the mandates for serialization down to the item level. Participants and presenters provided thought leadership from the pharmaceutical/biotech industry sectors, while experts in the area of digital technologies explored solutions.

A theme reinforced by each presentation was the increasing complexity of the chain of custody — and in many cases a chain of identity. Technologies addressing the challenges of collaboration and communication across a network of diverse entities were discussed from a variety of perspectives. The term orchestration platforms, used to describe common digital platforms and data integration tools, highlights the need for collaboration and real-time communication across communities of participants. The outcome, a shared view of the sequence of activities, with related reference data across the chain of custody and into the chain of care, was a common goal. This should effectively create a “digital twin” of the physical flow of raw materials and products as they circulate around the patient in the center of the supply chain.

Once the challenge of connecting the dots between the different players in an increasingly global supply chain community is mastered, there is additional benefit in the digital data. Presenters debated what to do with the oceans of data that could be shared in digital format. Artificial intelligence — or machine learning — was touched on in a variety of presentations, highlighting many opportunities to monitor trends and predict requirements across geographic regions and specific therapies. These present exciting opportunities for the life sciences community in general.

Addressing Issues Specific To Cell And Gene Therapies

Presenters focused on cell and gene therapies addressed issues specific to that sector. This therapeutic area includes small patient populations whose previously unmet needs are now being addressed by a combination of highly personalized and novel therapies.

Although many of these therapies are still in early stages — Phase 2 and 3 clinical trials — the subject of supply chain is one that challenges all constituents. The complexity of these environments — from starting material acquisition to delivery of drug product — requires new approaches and process innovation. Unlike traditional therapies, which are characterized by linear supply chains, with cell and gene therapies each functional element revolves around the patient, the clinical environment, and the caregivers who are integral to the patient journey.

Figure 1: Evolving models for a patient-centric supply chain for cell and gene therapies

Presenters and panels discussed the differences between traditional biopharma and cell and gene therapies, highlighting some of the critical elements. Whether autologous or allogeneic, the product life cycle is supported by a complex supply chain, from acquisition of the starting materials through to delivery to the patient for infusion and treatment.

Unlike traditional pharmaceutical and biotech manufacturing, where starting materials are inventoried and can be integrated into production planning, the timing and schedule for the acquisition of materials for cell and gene therapies have a high level of variability. Whether using patient-specific blood or donor materials, the scheduling and acquisition of these biological ingredients needs to be balanced with the requirement to align personnel and production resources. This is challenging, as many of the required details are generated by clinical resources captured on paper or multiple media, across a variety of information systems and networks. This lack of integrated systems and controls is currently addressed through a series of emails, telephone calls, and unstructured information that needs to be harmonized and aligned with the batch records of subsequent production steps. This is no simple task, and it is compounded by different activities taking place across geographic boundaries and time zones.

This complexity extends into the supply networks that deliver the final product to the point of patient. Even without the requirement for personalization (for potentially more mainstream therapies) order fulfillment for cell and gene therapies does not take place through traditional channels — in many cases the request for specialized therapies comes directly from the physician. This is a very different model and one in which the standard communication flow falls short. There is no room for error, and timing and communication must be flawless. Once an order has been placed, the patient needs to be scheduled for treatment, with product delivery aligned with the infusion process. In this environment, a cohesive flow of information through a responsive communication network from point of supply is critical.

During the course of the event, a resounding message was communicated:

• There are many options available to address these challenges; the key is to identify all the primary constituents and review the current and desired processes for information sharing.
• This can then be standardized using the technology and tools that are now available.

This is good news for those already integrating their communities into their information system environment as part of the global serialization initiatives.

Cell and Gene Therapies Require Communal Collaboration

This train of thought moved onto another track as I prepared for the second event on the circuit, the Annual Conference of the Bio Supply Management Alliance (BSMA). This is a highly focused organization of pharmaceutical manufacturers and the service providers that support the increasingly complex biotech research, development, and path to commercialization. In the past, the event has focused on the more mature biotech companies and their specific supply chain related challenges. For the first time, a track was added to support a growing interest in cell and gene therapy.

The program for the afternoon included experts engaged in the production and commercialization of cell and gene therapies, including:

• Heather Erickson, VP supply chain, Sangamo
• Laura Alquist, VP global supply chain, Kite Pharma
• Carlo Guy, global head, supply chain, Novartis
• Franck Toussaint, managing director, BioLog Belgium

Presented as an overview of some of the challenges being addressed by each of these organizations, the common message was clear.

• This is an immature supply chain environment requiring a different approach for design and development of distribution networks.
• Patient populations are small, the cost of the therapy is high, and there is no tolerance for delay or disruption.

A resounding theme was the need for increased collaboration, consistency at the process and documentation level, and stringent monitoring of time and temperature for all materials, from acquisition of starting materials — donor or patient blood and tissue — all the way through to final delivery and infusion at the point of patient.

Although a couple of cell and gene therapies have made it through the approval cycle and into commercial distribution, the majority of the therapies discussed are still in the exploratory and clinical trial stages. This creates its own challenges:

• Unlike more traditional clinical trials where patients are recruited and treated with drug product and placebos, in many cell and gene therapies the source material for the clinical trial product is blood or other patient material.
• In the case of autologous therapies, this is a batch of one — with the experimental product produced from the blood or other cellular material from each unique patient.
• Allogeneic therapies share many of the same challenges, further compounded by the complexity of retaining the digital DNA (or audit trail) of the source material, important for all cell and gene therapies.
• Ensuring product integrity is critical — each activity should be captured and recorded, reflecting time, state, and chain of control from material acquisition, transportation, quality control through transformation of biological materials to drug substance, drug product, and, finally, reconstitution and infusion at point of patient.

Centered around the patient, supply chain participants include caregivers who are responsible for the acquisition of biological material and the administration of the final drug product. They constitute a complex network of entities that use different information systems but are inter-dependent and need immediate access to accurate data and information across the vein to vein life cycle.

A follow-up conversation with one of the keynote presenters engaged in the development of a supply chain for two of the few commercial cell and gene therapies provided the following take-aways:

• Developing strategies for these “one size fits one” supply chains requires deep functional expertise and hands-on experience working in complex, global supply chains.
• This is a moving target — physical and digital networks need to be agile and responsive.
• Technology is an enabler, but global variations in regulations need to be understood and planned for.
• The cost of failure is high, not only in monetary terms but in potential lives lost.

Other presenters reinforced this message, highlighting the interdependence of the flow of material and information and coordination of clinical, production, and logistics resources across the chain of custody and control.

The focus of the final presentation of the day was the acquisition of the starting material — something that had not been reviewed in depth earlier in the day. Panelists represented three important constituents in these first links in the chain:

• Donor Community: Donor engagement and collaboration with clinical environments for the acquisition of the patient material, the starting ingredients for cell and gene therapy (Greg Bodnar, senior client engagement manager, Be the Match Bio Therapies)
• Clinical sites: Representing the patient experience, from acquisition of blood, tissue, or other materials to administration of the therapy (Heather Steinmetz, QA manager for bone marrow transplant, UCLA)
• Manufacturers: The production of new and novel therapies is fraught with challenges and although there are a growing number of therapies that are getting closer to the finish line, the list of companies with commercial products can be counted on one hand. (Grace Randhawa, tissue operations expert, Apheresis Operations, Novartis)

Each panelist reviewed challenges and opportunities they were facing, describing how they were collaborating with others in the industry to overcome obstacles to success. One of the biggest issues facing all participants — and the constituents they represent — is a lack of standards and common practices for the acquisition of material and the final administration of the drug product.

This is further aggravated by the variety of different information systems used across different manufacturers and the complexity of following different procedures for each clinical trial. Challenges include:

• Training and ongoing compliance with a variety of requirements
• Different procedures for the packaging, labelling and shipment of materials
• Complexity of temperature management and control — some materials are shipped at a controlled range of 2 to8 degrees Celsius, while others are cryo-preserved at the point of acquisition and shipped in LN2 packaging units.

A shared goal was a common system of record, which is something not currently available. Initiatives for serialization and tracking/tracing at the line item level are under development and promise to address many of these challenges. However, to date this is not a standardized process and variability leads to high levels of risk.

Conclusion

Although neither of these two events had conclusive messages, there was consensus in terms of what needs to be done, including development of common digital networks to facilitate collaboration, communication, and consistency across these integrated communities of clinical practitioners and the manufacturers and service providers that support this supply chain.

This is a call to action for practitioners and providers of services for digital networks, technologies, and applications. And it is one that I am sure will be responded to, no matter how difficult the road ahead. All constituents share a single goal — addressing the needs of the patient in the center of the cell and gene supply chain.

About The Author:

Carla Reed is a seasoned supply chain professional with more than 25 years of experience providing leadership and program management across a variety of programs for the life sciences industry. Her broad range of experience and expertise has provided solutions for pharmaceutical and biotech companies challenged by the growing complexity of extended supply chain environments. Her firm, New Creed LLC, provides change leadership to facilitate sustainable solutions, providing hands-on experience in all aspects of supply chain operations. You can email her at carla@newcreed.com or connect with her on LinkedIn.