Consistent management and communication are the keys to success when managing the supply chain of any advanced therapy clinical trial. In this article, we’ll review two case studies that demonstrate the importance of supply chain management by focusing on scaling up for commercial distribution and on packaging challenges within a cryogenic environment.
This figure shows the distribution and logistics workflow for an autologous therapy from the point of cell collection through manufacturing, packaging, and distribution to the clinical site. This demonstrates the many activities that occur both before and after drug manufacturing, all of which are critical components, and require careful management and strategic planning.
Reducing Risk in the Supply Chain
Reducing the risk to the product can be done at almost every point in the supply chain. For example, validation of equipment to standard process parameters reduces the risk by ensuring the storage equipment meets all required specifications. Validation of shipping lanes reduces risk by ensuring that customs clearance procedures, documentation, and transport methods are verified so the drug product does not get held or damaged. Overall, standardization of procedures (including collection, distribution, pack-out, and receiving/handling) can greatly reduce risk and variability in the process, which helps to reduce the total cost of the trial to the sponsor.
For autologous therapies, the challenges within the supply chain can be quite unique. Minimizing risk is absolutely critical for these therapies, as there is often only a single lot of drug product for a specific patient. These patient-specific therapies require unique labeling and packaging, which is often processed at the time an appointment is scheduled. This can drive up production costs, making efficiencies and control of these processes critical to managing cost. Additionally, the chain of custody is often more extensive for autologous therapies, as these are generated from a unique cell collection process.
Commercial Planning for Autologous Therapies
In our first case study, we’ll review the commercial planning for an autologous therapy currently in phase III clinical trials for patients with advanced renal cell carcinoma. The therapy is generated from a tumor collected from the patient, which is then transported to the manufacturing facility for processing into the final drug product. The drug product is then transferred at cryogenic temperatures to a storage depot, where it is packaged just-in-time for a clinical request. Challenges when planning for commercialization revolved around standardization of processes between vendors (for things such as labels, manifests, and handling techniques) and managing the just-in-time pack and label process for commercial distribution.
When planning phase III and commercial activity for this client, several components were identified within their supply chain that could be optimized to help control both risk to the product and cost to the sponsor. The first step was to standardize collection kits used by the global collection centers. By standardizing the kit components and having them distributed from a central manufacturer (which in this case was Fisher BioServices), we were able to reduce simple errors in the collection process, receiving time at depots, CMOs, and clinical sites. This standardization was critical to this trial and helped to ensure a consistent chain of custody from collection to manufacture of the therapeutic.
With regards to just-in-time secondary packaging, Fisher BioServices worked with the sponsor and the clinical sites to develop processes that worked with a current IVRS system. This helped to automate notifications of patient appointments, which allowed for faster, more efficient communication to the depots to begin packaging operations. Using validated shipping lanes assisted in determining the required transport time (depending on site location). The data gathered in these validation studies helped to drive operational processes to ensure that any shipments with a longer transport time were processed first; ensuring the patient dose is able to be given on schedule. By working to standardize processes and communication between all partners involved in this study, we were able to optimize the efficiency of the supply chain. This helped not only to manage the overall cost of the trial logistics, but also helped to ensure that each patient received their treatment on time and at optimal efficacy.
Planning for Allogenic Therapies
When planning for allogeneic therapies, the supply chain management challenges are different than those for autologous therapies but equally impactful. There are several key factors that can reduce the risk and the cost within the supply chain. One key area for cost reduction is standardizing labeling procedures. By using standard labeling such as barcodes, depots can reduce time and cost for sample pulls for distribution. This also aids in reducing variability and human error when QC checks are performed. Standardized processes also facilitate reduced cost by implementing efficient solutions for sample handling across multiple vendors.
In this case study, Fisher BioServices was working with a partner to manage the supply chain for an allogeneic drug that was going into a global phase III clinical trial. The challenge in this case was the cost of production and subsequently, the cost of the entire global trial. Production costs for biologics, especially advanced therapies, can be quite high due to regulatory demands, material and facility cost, and the time associated with process scale-up. This sponsor had decided to manufacture lots of drug product to support multiple countries within the trial, requiring country-specific labeling and packaging to be done at -120°C, or the drug efficacy may be compromised (based on stability data).
Keeping in mind the need for efficiencies and the temperature specifications for product handling, the teams of engineers at Fisher BioServices partnered with the client as well as a medical device developer to create a semi-automated process for secondary packaging and labeling that can be executed at temperatures colder than -120°C to ensure product integrity. The device developed also helped to reduce the total packaging cost by reducing the labor time required to package material by 50%.
The solution ultimately enabled our client to use a single production lot to support clinical trials in 17 countries. Additionally, the packaging process was designed to be scalable for use in commercial distribution, which helps to reduce any further development costs after phase III.
As you can see, advanced therapies pose many unique challenges to the supply chain. The keys to overcoming these obstacles lie in careful planning and central management of the entire supply chain.