Note to readers: A short laymen version of this article with suggested problems and proposed solutions is published in Crain’s Cleveland Business. Here, we present a situation assessment for more advanced readers.
If George Orwell were alive today, he could have pointed out that ‘all viruses are equal, but some viruses are more equal than others.’
In May, at the annual meeting of the American Society for Gene and Cell Therapy, presenters discussed viral and cell manufacturing almost hourly. They concurred that demand for the capacity grows much faster than the supply. As a result, the industry enjoys high profit margins and struggles to hire enough full-time employees. We just cannot get enough of these living therapies.
Many organizations are building their own manufacturing capacity for gene and cell therapy products. Ohio is not an exception. Academic and for-profit organizations are expanding their scale and compliance level. Ohio is not quite at the level of the East Coast hubs, such as Cambridge and Baltimore, but it is definitely an up-and-coming state in regards to cell and vector manufacturing.
However, not many people in the state realize the scope and the future impact of this transformation. I interviewed key manufacturing experts in the region with the goal to summarize current state and future plans for the industry.
Ohio Cell Manufacturing
Below, two maps show Ohio cell manufacturing landscape, as of April 2020. We included only non-minimally manipulated cell production that requires substantial expertise and infrastructure. To see expected capacity and expertise expansion, toggle between TODAY and FUTURE. (for full-screen, click on the low right corner).
Looking into the future, CWRU and Abeona are considering expansion. Also, Cleveland Clinic (CCF) has capabilities to handle commercial CAR-T products, and it would be interesting to see if CCF expands its capabilities beyond minimal manipulation. Finally, people across the state are talking about Hitachi potentially bringing commercial-scale cell manufacturing capacity to the region. However, no plans have been publicly announced to the best of our knowledge.
In my opinion, having a local commercial manufacturing organization (CMO), like Hitachi, is a huge plus for Ohio. First, non-profit academic center should focus on what they do best, i.e., being flexible and innovative, supporting translation and early proof-of-concept trials of small scale. Second, currently, technology transfer (from a university to a CMO) takes most novel technologies outside the state. Therefore, the region does not capture profits generated from GMP manufacturing of those products.
Ohio Vector Manufacturing
Below, two maps show Ohio vector manufacturing landscape, as of April 2020. Many facilities are able to handle vectors using dedicated clean-rooms. However, here, we included only facilities that engage in vector production. To see expected capacity and expertise expansion, toggle between TODAY and FUTURE. (for full-screen, click on the low right corner).
Key non-profit vector manufacturing players are, not surprisingly, NCH and CCH. NCH is a well-known leader in adeno-associated virus (AAV) research and manufacturing. Whereas CCH is leading lentiviral vector (LentiV) production in the state, supplying customers locally and nationally.
Among for-profit companies with vector GMP capabilities, Abeona Therapeutics manufactures AAV for its own clinical trials in Cleveland. Additionally, Sarepta announced building of 85,000 sq ft R&D space in Columbus. Its website indicates that 80,000 sq ft are dedicated to manufacturing.
Future is bright for AAV. Two new commercial players are planning on building manufacturing facilities in Central Ohio. First, Andelyn, an NCH’s spinout, aims to ramp up AAV production for pivotal trials by est. end of 2021 and commercial production by est. 2023. Second, Forge Biologics aims to build commercial capabilities for AAV to support a broad range of customers.
Key Challenges
Even though Ohio manufacturing facilities strive to differentiate from other local players, all of them continue to share common challenges. Currently, challenges include time, space, staffing, and, most recently, COVID.
Time
Delays in cell and vector production are very typical for the industry.
First, you wait for the open slot to start the production. This may take a month to a year or more. On the map, we showed typical queue times for some facilities.
Second, it takes time to make and release a product. This time may vary. For example, it takes a month to make a lentiviral vector and then additional ~4-6 months to certify it. The biggest delay is getting results from independent testing labs – these labs are overwhelmed.
Space
Space is valuable, but freezer space is even more so. For example, vector production requires large quantities of materials taking up a lot of freezer space. In cell manufacturing, production of allogeneic natural killer cells may require the use of feeder cell lines. Feeders occupy a lot of freezer space; they also require very skilled handling due to being cancer cell lines (usually, AML).
Staffing
Qualified and experienced technologists are a rare breed. Every expert I have spoken with agrees that staffing is always an issue. There are just not enough people who has such training, and there are almost no educational programs (either 2-year, BS, or MS) that prepare qualified techs for cell and vector manufacturing jobs. Between competitive salaries, fluctuating demand, and training needs, getting enough FTEs is just a hard sell for most non-profit facilities.
COVID19
Finally, COVID has been a huge challenge for the facilities. Most of these facilities are part of a hospital. Thus, they are focusing on providing therapies, while de-prioritizing or putting on hold other activities, such as R&D and contract manufacturing.
First, the facility staff is cognizant of using personal protective equipment, saving it for more urgent hospital needs.
Second, social distancing requirements force facility directors to stagger shifts, slowing down the work. Additionally, when one person gets sick, everyone the sick person worked with in the past week may need to stay in isolation for a while.
Lastly, many activities such as training, aseptic process validation, process development are non-essential and on hold.
As a result, many cell and vector products needed for clinical trials will be significantly delayed.
In summary, here, we presented a situation assessment for cell and vector manufacturing in Ohio based on primary and secondary research. A short laymen version of this article with suggested problems and proposed solutions is published in Crain’s Cleveland Business. Below is a high-resolution map for non-experts.
We welcome any comments, corrections, and feedback to help us build the complete picture of Ohio cell and vector manufacturing landscape. To find more articles visit our Insights page.
Disclaimer: This article is for the educational purpose only. It is the property of BioHeights LLC. This article is written based only on non-confidential information including public announcements, websites, press releases, non-confidential interviews with manufacturing experts in the region. BioHeights LLC and its members are not responsible for any damages resulting from reading this blog article. In addition, this article may be missing certain information that interviewees and public announcements chose not to disclose. BioHeights LLC takes no responsibility for completeness or correctness of this article, these maps, and information they contain.
