Advanced therapy medicinal products (ATMPs) made from human genes, cells, and tissues are providing impressive results in patient treatments. Opening presentations of this year’s annual meeting from the Parenteral Drug Association (PDA) included an emotional talk from Tom Whitehead, the father of a girl who beat leukemia through CAR-T cell therapy. Emily Whitehead, now 15, has been cancer-free for eight years.
These scientific breakthroughs also come with significant changes to traditional manufacturing processes and drug supply chains. Added to a traditional drug supply chain model are new levels of complexity as the raw materials for these drugs are cells or tissue coming from the patient, as is the case with the autologous CAR-T process used in Emily’s treatment; or a donor, as with an allogeneic hMSC product process that can be used for multiple patients.
Traceability begins when the cells are collected and continues through manufacturing, packaging, transport, and administering to the patient. “There’s little room for error because this might be the patient’s last chance for survival,” said Monique Sprueill, senior manager of strategy, insights and innovation at Johnson & Johnson.
Sprueill spoke at the PDA Annual Meeting—held virtually because of the COVID-19 pandemic—about data and risk management in the drug supply chain, focusing on the particular complexities of ATMPs. There’s a complex web of interaction that needs to occur in the supply chain. Though that’s true through much of the pharmaceutical industry, she noted, it’s especially critical in the case of patients being treated with these innovative methods. “We’re working with shorter timelines and patients that are very sick,” she said. “We need to make sure we deliver the medicine as quickly as possible and it needs to be effective for that patient.”
The ATMP supply chain faces challenges in planning and forecasting; vendors; raw materials; manufacturing, packaging, and labeling; logistics; and storage. Because it’s a patient-driven process, there’s some level of uncertainty in the forecasting process. But targets need to be set nonetheless, Sprueill said. “Schedules must be closely monitored due to patient changes,” she added. “There need to be plans to communicate changes, adjust schedules, and align as necessary. Order and management are integral to the end-to-end process.”
Supplier quality standards are not always aligned with expectations, Sprueill noted, so it’s important to communicate sourcing requirements and understand vendor capabilities. “With cells and tissues collected from patients and donors, they become part of the raw materials,” she said. “You need to make sure agreements with all parties are in alignment and use standardized procedures whenever possible.”
One major challenge is cell variability from patient to patient, which can result in lower yields. Sprueill advocated using automation in closed-loop processes and also using advanced analytics to correlate data with desired outcomes.
“An additional challenge is the turnover time is shorter,” Sprueill said. “It’s very important to make sure people working on the process are adequately trained. And make sure the expertise is there to minimize errors during the process.”
The final product is a single batch—one that has to be transferred at cryogenic temperatures. “If you’re using multiple vendors, it could cause issues,” Sprueill noted. “Look for opportunities to standardize processes where possible and minimize the number of vendors.”
Supply chain management
Across the entire supply chain, the use of data and analytics is key. “One thing that has to occur throughout all processes is chain of custody and chain of identity,” Sprueill said. “Who provided the starting material? You need to make sure that same material is administered to the patient.”
It’s also important to track where the material has been, how long it took to get from one place to another, and who touched it along the way. “Data and analytics are a way to make sure you keep track of the chain of custody data,” she said, but they also track quality, vendors used, raw materials, where it’s packaged, controls put in place, tracking material, interactions, handoffs, storage, temperature conditions, and more.
Because the cells are temperature-sensitive, it is key to make sure there are trackers. “Temperature sensors offer information that can be used if there is a delay in shipment. When you’re not able to maintain conditions, deviations are written and proper investigations are performed,” Sprueill emphasized. “You have to adequately describe the impact of those deviations. There’s little room for error. We make sure we’re as careful as possible, but also have the documentation to demonstrate that appropriate controls are in place and procedures are followed consistently.”
Data can be used to monitor outcomes but also to put procedures in place to modify the process if there are issues with the outcome.
“Having data that tells a story, is informative, and is able to be communicated at the right time to the right people helps drive key quality decisions,” Sprueill said. A robust supply chain management system ensures that patients receive the products they need. “This is a lifesaving or life-sustaining product and it means the world to someone because that patient means the world to someone.”
>>Read more about supply chain concerns in new drug modalities from last year’s PDA conference in “21 Critical Supply Chain Tips for Cell Therapies.”