Rapid growth in the cell and gene therapy industry is driving the demand for more efficient and cost-effective manufacturing solutions. Last week, Cell and Gene Therapy Insights hosted a webinar, Automation of cell & gene therapy manufacture: Challenges, options & opportunities for innovation, where panelists shared their insights on bioprocess automation. Here are some of the highlights of that discussion along with insights we have gleaned from our interviews at institutional and commercial manufacturing facilities, cell therapy companies and other industry organizations.
Cost and process complexity are two of the main reasons to implement automation, say both Brian Hanrahan, Program Manager at Invetech and Mary Murphy, Principal Investigator, Regenerative Medicine Institute, University of Ireland. And according to an industry survey these are also the top two barriers to implementation. While bioprocess automation is costly to implement, it can dramatically reduce manufacturing costs in the long-term, Hanrahan explains. Automated, closed single-use systems can reduce direct labor costs by 40-90%. In addition, these systems reduce the cost of the facility required for the manufacture of cell and gene products. There is a 5-fold cost difference between leasing a Class B space for open, manual processes and a Class C space for closed processes. Savings on owner-occupied facilities are even greater. At Nelsen Biomedical we recently analyzed the primary drivers of manufacturing costs. In our interviews, facility and labor costs were cited as the largest percentage of manufacturing costs, at least for small-scale manufacturing. So, decreasing these costs could have a significant impact in reducing Cost of Goods Sold (COGs).
What to Automate?
Hanrahan says that it is unlikely that everything about the manufacturing process will be amenable to automation, because in cell therapy one size does not fit all. So, he recommends that companies identify complex steps in the process where there is inherent variability and prioritize these for automation. In addition, consider which parts of the process automation will be able to be integrated at the commercial scale. We also note in our interviews when we asked, “When does bioprocess automation make sense?” leaders in process development and manufacturing cited two areas where bioprocess automation is important:
- Steps that are difficult to validate in GMP
- Steps that are time consuming or laborious
When to Automate?
Implementing bioprocess automation has to be a business driver for the company – e.g. better COGs, quality, throughput, etc. explains Biren Mistry, Senior Bioengineer at Celgene. In Phase 1, getting clinical data as fast as possible is typically the goal. But Phase 2 is a critical inflection point in developing a cell therapy, and this is the time to invest in automation. Any earlier, in his opinion, and the money is likely better spent on research and clinical trial activities.
Others suggest it is never too early to anticipate automation. Kate Sneddon, CEO at Biovault Technical Ltd. cautions that companies should prepare and design for automation early on. She says that cost becomes prohibitive when doing so many units that it becomes difficult to change over to automated methods. Biovault is currently using a semi-automated approach to process umbilical cord blood and is looking to switch over to fully-automated. This transition could have happened sooner if they had planned ahead.
The Future of Automation
Panelists believe that we will see bioprocess automation in place in next 5 years. To get there the industry needs:
- Real successes at the clinical level to drive investment in automation.
- More systems and solutions for upstream, downstream and analytical functions.
- Increased collaboration:
- Across different parts of the supply chain to integrate the entire process.
- Industry consortia. These have been important in Europe in regards to providing funding and private-public collaborations. For more on how these private-public partnerships drive manufacturing improvement see here.
The consensus from our interviews with key leaders in this field is that the industry is headed away from clean rooms and toward automated, fully enclosed systems that can manufacture cells from multiple patients, or for multiple programs, simultaneously. Bioprocess automation will reduce contamination and process variability, facilitate cell qualification and regulatory compliance, and allow parallel processing. The result? Increased manufacturing throughput, reduction in COGs, and commercialization of clinically promising cell therapies.