Standards necessary to guarantee the volumes and quality of the raw material
Adding capacity, boosting efficiency, and reducing bottlenecks within the cell harvesting infrastructure are key to ensuring the availability of high-quality starting material, the company said. , which provides cell supply services for allogeneic cell or gene therapy, as part of its range of services. .
Any misstep in this area can lead to significant and costly setbacks and delays.
Optimizing the identification, procurement, collection and delivery of starting material from allogeneic donors is therefore essential, said Chris McClain, senior vice president, sales and business development, BTMB.
âAt this time, no one knows exactly who or what consortium of suppliers may be able to deliver the potential trade volumes. An additional challenge will then be to guarantee these volumes in a consistent and high-quality manner.
“We, as suppliers, are working on this issue, but we also need the participation of the industry”,he told BioPharma-Reporter.
He calls on cell and gene therapy (CGT) developers to step up their engagement with BTMB and other suppliers to develop standards as part of efforts to ensure a reliable supply chain for raw materials.
“Right now there’s a lot of customization, a lot of customization in terms of allogeneic donor seed request requests and I think it’s not sustainable, and I would bet a lot of things are unnecessary.
âLet’s eliminate what is essential and what is not for the betterment of the industry. “
There are a variety of different starting materials that the developers of CGT might want to craft with: from whole blood to stimulated apheresis to bone marrow to basic blood units.
âThey might all be great vehicles for manufacturing, but within each category what we, and I believe other suppliers, are observing is that companies are experimenting with the specific criteria they would like. Within each category of donors, some want donors who match a certain demographics, often resulting in the use of more sophisticated screening panels, such as genetic panels.
âAnd while we have to constantly remind ourselves that the field is trailblazing, innovating quarterly, and there really aren’t any proven ways to do a lot of that, the question, on the supply side, is how many of these [multiple and varied demands] can we stand?
“For example, if we have 15 customers who all want an unmobilized apheresis product – a leukopack – but each of them wants something slightly different in that leukopack, then that can be done, it’s going to take a lot of time. time and it’s going to be expensive.
“And if that’s the model for the future, then you might have a potential scenario where each of those 15 companies would have an approved product, and they’d increase all of their demands for their particular type of donor by a factor of 10,” or even 15 times. I just don’t see such a model working â,McClain pointed out.
Companies can also request that the harvest take place on a specific machine, using specific tubes and bags. âWe all understand that: the manufacturing of these drugs is highly regulated and you don’t want to change the process. But does it really make a difference if the specific machine, bag and tube are used? Probably not. We, as an industry, may therefore seek to standardize these aspects in the future. “
And the industry could also seek to standardize in terms of donor characteristics, McClain added.
Standards development projects
Before the pandemic, the BTMB hosted the AcCELLerate Summit,where he brought together industry stakeholders to advance standardization efforts in the CGT space, said McClain, the executive acknowledging that there are currently a number of standards development initiatives.
Some of the most significant ongoing projects include the initiative led by the FDA-funded organization, Standards Coordinating Body for Regenerative Medicine (SCB); it seeks to identify and understand the areas most in need of standardization to help the industry move so quickly, to the benefit of patients.
The ASTCT recently launched a standards development initiative, and management consulting firms, Accenture and Deloitte, both have similar efforts underway, with additional work in the space being done by smaller groups at across the EU and the US, the BTMB executive said.
However, such work, McClain pointed out, requires a lot of resources and it is difficult to achieve consensus on many issues from the multiple actors involved in the field. “BTMB is in the middle, we lead in some cases, we participate in others.
Building donor pipelines
Another constraint he highlighted is the fact that many organizations do not have decades of experience in building value chains with thousands of donors.
The strength of BTMB is that it is a business unit of Be the Match, a group essential to the global ecosystem of bone marrow transplants and hematopoietic stem cells, and which relies heavily on allogeneic donors, has he declared.
âIn the case of Be the Match, this involves more than 6,000 donors per year; we must guarantee them for the benefit of patients with leukemia and lymphoma. So as an organization we are very good at it. We have built a pipeline through which we can acquire thousands of donors each year for the special purpose of bone marrow and hematopoietic stem cell transplants. We are unique that way; the rest of the cell therapy industry has not been in a position where organizations have had to acquire this number of donors per year for all therapies because they are all still in clinical trials. The number of patients who could be treated prospectively in a clinical trial for cell therapy could be 100 people over two years, and this requires a very different set of processes than what is required to acquire more than 6,000 donors per. year.
âSo we have experience in this area and the BTMB is the avenue through which the emerging cell and gene therapy industry could tap into this infrastructure. “
But, regardless, a bottleneck remains: the lack of providers who could supply thousands of donors to support commercially approved cell and gene therapy, he added.
âBasically, the offer doesn’t exist. We will be one of the greatest players [in the CGT space] but it is also a new enterprise for us.
In addition to these challenges, there is the question of the capacity for apheresis.
The US national capacity for apheresis has never been built with approved cell therapies for prevalent solid tumor cancers – lung or breast – in mind, where hundreds of thousands of patients could be treated. every year, he noted.
“There is not enough capacity in the American network, not even close, to collect so many donors, whether they are autologous or allogeneic. There are not enough machines or beds, and there are not enough staff. I think that the industry must be ready to invest in this infrastructure to secure this critical capacity because, for the moment, it is only an addition to the existing infrastructure â,McClain commented.
For comparison, he noted how, compared to the CGT manufacturing bottleneck, with limited contract manufacturing capacity and labor-intensive and man-intensive production processes, the industry was quick to find solutions.
âHow has the industry reacted to the manufacturing bottleneck? These are developers who raise hundreds of millions of dollars and build their own manufacturing facilities. It is happening all over the industry. So maybe companies can raise hundreds of millions and dollars and invest in their own apheresis centers as well. It goes hand in hand with manufacturing.
In the field of allogeneic cell therapy, there is still hope, however, that the requirement for a massive amount of donor material could be drastically reduced if the end product created from a single donor can be. expanded, stored and used to treat multiple patients, McClain commented.
âMaybe from a handful of a few donors you could make thousands of therapies. If this is the case, if this is the future, of course the simple math is that the ability to apheresis is much less of a problem.
“At the other end of the spectrum, however, there are allogeneic cell therapies that rely on building inventoried cells in banks and these will continue to need increasing volumes of donors just to maintain the bank.” cells. So it depends on which model wins.
Sanjay Srivastava, who heads Accenture’s global center of excellence in cell and gene therapy and its consultancy firm, will address some of these bottlenecks in our free access to the webinar On cell and gene therapy on December 1.