October 11, 2018
Neox attended our first Cell and Gene Meeting on the Mesa in early October. Over 1200 attendants gathered at the beautiful Estancia Hotel in La Jolla, and the conference covered a range of topics from market access and reimbursement to the latest discoveries in gene and cell therapies. I heard from many attendants that the meeting has grown significantly, especially this year. In 2019, the meeting will move to Carlsbad to accommodate the expansion of vendors and vendors in this field. The Meeting on the Med in Barcelona in April 2019 was also announced, again reflecting the global growth in the regenerative medicine industry.
The workshops brought together panelists to share their lessons learned from many aspects of regenerative medicine and advanced therapy, including funding, manufacturing, and patient engagement. During the session on developing clinical programs for cell and gene therapies, panelists discussed how cell and gene therapies differ than traditional pharma products, in that they require more submissions, higher rounds of review, specialty labs and assays, intense site training, longer patient consent processes, and are associated with higher costs/patient and higher costs/site. In addition, global regulatory frameworks are less harmonized. To provide a perspective from the FDA, Dr. Marks spoke on their current initiatives at CBER, like the INTERACT program, which is a nonbinding discussion between companies and the FDA, without the formality of a pre-IND meeting. He also referenced FDA’s recent guidances on regenerative medicine and gene therapy.
US-based trials for cell and gene therapies can be lengthy. From the perspective of one panelist, it is not uncommon to experience a timeline of 12-18 months from site selection to site opening. Cell and gene therapy trials require longer approval, and sometimes other activities, such as site training, cannot be completed in parallel to IRB approval. Biocardia has “protocolized” the company’s site selection and recruitment process, which involves building a strong clinical team who are invested in the risk benefit of the therapy. They developed a formalized training protocol that interacts with departments involved with the procedures associated with the study, to design a normal workflow. A panelist from WuXi provided a manufacturing perspective, in which he described the workflow as knowing the “chain of identity”. For example, who will author the SOP for the cell processing and handling? How will that SOP change during transit of the therapy? How will those process be implemented at hospitals, where the settings are more stringent and often require one cell processing suite/patient? As academic centers have the capacity to drive manufacturing processes, enabling spin out companies from the bench, how will they format their SOPs? Concerns related to documentation of cells preparation and hospital training records were also discussed. Would GCP documents be used as a general template, as there is no current industry standard?
Trials outside of the US can also be lengthy. One of the panelists listed a number of challenges specific to the EU: approaching 15-20 member states, delays in approval, GMO, timing, and expectations for long-term follow-ups being the same as in the US. Challenges in patient recruitment are true for most indications. In the US, the standard of care is changing. Combined with the competition among companies to recruit, as often companies may be targeting the same patient with cell in gene studies, recruitment continues to be a hurdle.
As innovation and cell and gene therapies advance to the clinic, manufacturing plays a major role in getting these treatments to patients. Challenges in the supply chain for advanced materials include growing volumes, growing geographies, and increased temperature needs. For example, World Courier predicted that the industry would see imports in Central and Eastern Europe in the next 5 years. Increased temperature needs refer to the changing landscape in temperature shipping, specifically using colder temperatures to increase shelf-life. It was eye-opening for me to see the complexities of an autologous cell therapy supply chain mechanism, from screening of the patient, physician trainings, to freezing therapies, QC, transport from/to hospital and to/from manufacturing and how they all fit together to ensure a chain of custody and clear responsibilities among all parties. Specific hurdles can affect the entire process, such as issues with transportation unions going on strike during a delivery or the infrequency of advanced therapy procedures performed at hospitals for site staff to become familiar with the activities. Even in this space, automated, digital platforms are available to help various activities of the study: capacity and planning, scheduling and collection, in bound logistics, manufacturing, outbound logistics, and confirming completed orders.
Looking forward to next year’s meeting!