It’s been over a year since the outbreak of the novel coronavirus in China and its spread to all corners of the world. During that time, a phrase once confined to the business world has now become part of everyday parlance: supply chains.
We’ve seen the impact of supply chain disruptions in food, hygienic products—and most recently—the distribution of the latest COVID-19 vaccines. But the COVID-19 supply chain situation has also brought to the forefront issues known by scientists, researchers and the many contributors in the evolving therapeutic area loosely defined as cell and gene therapy (CGT). The complex Pfizer and Moderna vaccines, developed with messenger RNA for example, share many of the challenges that other less publicly known therapies face.
One of the biggest challenges for CGT therapies is the availability and viability of starting material.
These therapies—used in the treatment of lymphoblastic leukemia, spinal muscular atrophy, retinal dystrophy, and other diseases—are often developed using human cellular material that has a level of complexity not found with traditional pharmaceuticals. Other biotech therapies use different platforms and production mechanisms that—although complex and delicate—do not have as many risk factors as these CGT therapies.
Building New Patient-Centric Supply Chain Models
Traditional supply chain models no longer apply with CGT therapies. This new patient-centric model begins and ends at the point of patient. Literally. It’s called “vein-to-vein” because these supply chains begin with the extraction of human material—the starting materials (or active ingredient). Different therapies use a variety of human materials, including blood, human tissue and organs.
Materials are both time-and-temperature sensitive and supply chain coordination is absolutely essential to ensure success.
One of the biggest challenges for CGT therapies is the availability and viability of starting material. This can include patient-specific therapies using human cellular materials from the same patient. For example, in a process called “apheresis,” blood is extracted from a specific patient, then processed and transported to the production location for individual drug substance production in a form of personalized therapy.
Alternatively, it could be donor cellular material, including blood, skin, tissues and other biological substances. Either way, these materials are both time-and-temperature sensitive and supply chain coordination is absolutely essential to ensure success.
In addition to the biological starting materials, there are many other reagents and materials used when analyzing and processing that need to be sourced, procured, received and stored in specific environmentally controlled conditions.
7 Key Steps to Maximize Supply Chain Efficiency
There are also additional process steps that should be planned for and built into the standard operating procedures and ways of working. For a new product, it’s important to perform a detailed process review and risk analysis.
Based on our experience working with several biotech firms, we recommend a number of steps to help ensure maximum supply chain efficiency, starting with evaluating each of the items that are part of the bill of materials and their relationship to the production process:
- Evaluate the relationship between each of these items and the materials, ingredients and/or products they are related to.
- Consider inventory planning approaches already in place for these items and the cost to procure and hold this in appropriate quantities to meet projected demand.
- Review your relationships with direct suppliers—and related extended suppliers contributing to this supply chain—right down to the first participant (the patient or donor).
- Develop a supplier profile including both source of production (or patient/donor location/clinical site) as well as risk factors potentially impacting supply security.
- Categorize these suppliers based on strategic impact: high- and low-risk suppliers.
- Develop alternatives if possible (in many cases there are sole or single supply sources) and/or how to secure supplies in case of disruptions.
- Contact all key suppliers and engage in open and honest conversations. Develop strong relationships where possible.
Each of these steps should be integrated and formalized into work instructions as part of your standard operating procedures. Due to the criticality of the starting materials—and the requirement for quality control and assurance—this is a teaming exercise that should include internal and external entities.
Partnering to Acquire Materials for Clinical Trials
The current CGT transition model from discovery to distribution includes the participation of a contract development and manufacturing organization (CDMO). These companies are well versed in the complexity of the material acquisition process, which requires partnering with medical institutions—in many cases the same partners that collaborate in clinical trials. They also frequently develop relationships with specialized cell banks and donor management organizations, like “Be the Match.”
Because many of these activities often take place in more than one facility, additional planning … is also required.
Once material has been acquired and production initiated, you need to consider other supply chain factors, such as the starting materials used to develop the drug substance, including a ”bulk” format in bags, bottles or other configurations used to process and package the final drug product.
Because many of these activities often take place in more than one facility, additional planning for the packaging, labeling and transportation of these fragile substances from one link to the next is also required. At this stage, the critical path is shipment planning, ensuring that the material is transported and stored within the optimal temperature range as well as protected from a variety of environmental hazards.
As with the material acquisition, shipment planning should be coordinated with transportation providers as well as the receiving location to ensure that each step in the process is risk-assessed and mitigation strategies are planned for. This includes an extended, end-to-end process flow—identifying transportation modes, material-and-item handling, QC inspection and storage destination requirements. In some cases—especially for drug products—these destinations could be a clinical site where synchronization for patient preparation and infusion requirements need to be considered.
One of the most important aspects of the shipment planning process is understanding the material stability profile, potential environmental hazards and risk factors. Appropriate packaging elements need to be defined to mitigate against these risks, including temperature monitoring and control as well as smart technologies to enable the real-time track, trace and management across each leg of the transportation cycle.
Supply chain management challenges need to be overcome quickly for some of science’s best advancements to have any impact in the real world.
Coupled with GPS, applications, data acquisition and reporting tools, this facilitates a “real-time” view of the location, state and any exceptions to or deviations from the shipment plan. Available technologies include smart-time and temperature-monitoring devices, many of which also monitor other hazards, including tilt, light exposure, impact and shock. In addition to a digital record, the identity and control of each shipment can be used to qualify a variety of packaging configurations and variations across seasons.
During the clinical trial process, these source and destination locations are relatively predictable. It gets much more complicated, however, during the final post-approval commercial production stage. Depending on the nature of the therapy, the targeted patient infusion population could be very small and distributed across an extended geographic region creating special challenges. In these situations, there are additional considerations for product storage and distribution. These challenges need to be addressed as they evolve.
Today, “vein-to-vein” cell and gene therapies are among healthcare’s most cutting-edge solutions. But as the world’s COVID-19 vaccine distribution has shown, supply chain management challenges need to be overcome quickly for some of science’s best advancements to have any impact in the real world. The time to start is now.
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