Timing, technology, and partners: when it comes to process development, all three are worthy of consideration. Learn from Gary M. Pigeau, Ph.D., who discussed each of these considerations in a recent webinar.
A successful path to commercialization isn’t accidental; it’s paved with intricately thought-out bricks.
And before the cement dries, it’s important to optimize process development (PD) — prior to scaling up or out — to help ensure you don’t scale your inefficiencies. In a recent webinar, Gary M. Pigeau, Ph.D., Director of Research and Development, Nucleic Acid Therapeutics at Cytiva outlined three key considerations for PD optimization: timing — evaluating a realistic timeframe, technology — supporting your organization’s immediate and future growth strategies, and people — choosing the right PD partners and onboarding staff to meet operational efficiencies.
This case study assumes that a customer has already established a proprietary CAR and that they have a handful of host cell lines for the lentivirus (LV). The work done in the customer’s lab has been performed on a small scale in well plates or T-flasks and has shown promise in various models. They have the funding to move ahead with PD and the manufacturing of this asset.
In the webinar, Pigeau outlines four phases of therapeutic development and associated timelines to consider, each of which build off each other: LV manufacturing PD, CAR T manufacturing PD, LV Good Manufacturing Practice (GMP) manufacturing, and CAR T GMP manufacturing. In this article, we’ll mostly focus on the CAR T manufacturing PD and CAR T GMP manufacturing timelines.
However, a consideration regarding the first scope of work (SOW): “You can’t start CAR T work until you have a virus and a method to produce the virus,” notes Pigeau, “and the LV manufacturing PD phase is meant to address that first part.”
Following LV manufacturing PD, the CAR T manufacturing PD has an estimated timeline of eight to nine months, with five months dedicated to process development and optimization. “The individual tasks in Phase two can be optional, depending on the background development performed by the customer,” says Pigeau. During the last stages of the LV GMP manufacturing SOW, lentiviral master banks are manufactured and tested. That batch is then released in the last task of this SOW, which leads into CAR T GMP manufacturing.
The CAR T GMP manufacturing SOW — which culminates with a Phase I clinical trial — has an estimated timeline of one and a half years. From initiating process development with the CDMO to manufacture for a clinical trial, the proposed timeline is roughly two and a half years. This is dependent on how you interface with your CDMO, the current state of your technology, and what needs to be developed and characterized.
PD timelines greatly affect the overall journey to market. With patients waiting for these treatments, in addition to the cost of additional time, there’s high value in the efficiency of every step of your process.
Overall, Pigeau recommends that you “Keep in mind the initial time required to establish all the agreements that are going to define your journey. Be transparent about the GMP-readiness of your technology, and if you are not ready for manufacturing, choose a partner with PD facilities and experience with technology transfer.”
When considering cell therapy manufacturing technology, it’s essential to think about your organization’s immediate needs and future growth strategies. Scalable, functionally closed, and flexible systems are becoming more prevalent as the industry matures.
Pigeau points out that moving a process into a bioreactor takes work, so the sooner you consider implementing automated, closed, and scalable systems, the better. “The cell and gene therapy industry has seen tremendous growth. However, many processes remain open and manual, and require highly skilled, manual interventions. As more therapeutics enter GMP manufacturing, we will see maturation of the manufacturing processes to closed and automated, with minimal operator intervention. For today’s therapeutics developers, there is an advantage to invest in compatibility with closed and automated solutions early in pre-clinical development, as this will facilitate the transition to the evolving GMP manufacturing paradigm.”
When looking to develop your process with a CDMO, the first thing to keep in mind is the people. “Your first interaction is likely to be with someone from business development,” explains Pigeau. “This should be followed by conversations with a subject matter expert who can engage the developer’s experts in technical discussions.” The key with these conversations: transparency and collaboration. Any risks should be well-communicated and understood by both parties.
In addition to communication, it’s important to choose a partner with the facility and services that align with your needs. There are CDMOs that offer both PD support and manufacturing capacity, while others focus strictly on production.
Pigeau notes, “In preclinical or early-phase manufacturing, there are opportunities for continuous improvement programs, so a facility that offers both PD and GMP manufacturing is beneficial.”
Once you’ve chosen a partner, you’ll need to have a set of documents in place that capture key details relating to the work that will be done. Typically, the agreements required for this arrangement are the:
Confidential disclosure agreement
Master services agreement
Scope of work (SOW) — including the project change order and the material transfer agreement
It’s worth noting the time needed to negotiate these agreements, which can be additional months to a year, and is not included in the case study timeline (Figure 1) above.
“Ultimately,” says Pigeau, “it’s important to choose a partner that’s experienced in the science and manufacturing of your therapeutic.”
Another component to consider: your — and the CDMO’s — staff. With the large talent gap looming over the cell and gene therapy industry, the question of how to reduce / mitigate turnover is crucial for consideration.
So, how can you address concerns stemming from the talent shortage? One way is proper onboard training and guidance. PD success, and the success of your commercialization journey, is related to the development of talent dedicated to long-term employment. Improving the capabilities of your team and strengthening their confidence in the organization is foundational for success. Specifically, GMP continues to be a training gap for process development graduates. This knowledge is both essential in the biopharma industry and required by regulatory bodies. Learn how Fast Trak™ training can help fill that knowledge gap. Our Online Advanced CELLT1 course is an excellent resource to help onboard your staff in cell therapy. This free online learning course provides instruction within cell therapy processes under GMP. Typical workflow steps such as cell isolation, expansion, harvesting, and cryopreservation are covered. In addition, we also offer an instructor-led hands on cell therapy course to assist with your training needs.
Our Enterprise Solutions offering is designed to assist you, whether you’re scaling up — or out — to prepare for clinical trials and/or commercialization. Our equipment enables functionally closed and automated workflows, which may facilitate regulatory compliance. Plus, the equipment is flexible — it can support multiple cell therapies. Our mission is to propel you to your next milestone and into the clinic.
The three pillars of our Enterprise Solutions include the FlexFactory™ platform, Fast Trak™ services, and KUBio™ facility. These three pillars come together to provide a comprehensive solution including equipment, integrated services, and staff training to solve challenges encountered during scale-up, scale-out, manufacturing, and site expansion. Click here to learn more about Enterprise Solutions.