Cell Therapy
Clinical Trials
Raw Materials
Supply Chain

Innovation in an Integrated and Robust Clinical Trials and Biomaterials Solution

18 January 2022
Brandon Harper – COO of Cenetron Diagnostics, Versiti Suite of Services – and Dan Waxman – Vice President and Senior Medical Director of the Versiti Blood Center – discuss key challenges facing the delivery of clinical trials, and biomaterials supply.

Brandon and Dan explain how an innovative, integrated and collaborative approach is crucial for the continued scale-up in advanced therapies, as well as lessons learned from interruptions to clinical trials and biomaterials delivery supply due to the pandemic.

What are some of the key challenges or obstacles facing clinical trials right now?

BH: I think it’s probably speed to market and efficiency of the processes. It’s such a competitive landscape right now that getting your drug approved as quickly as possible obviously benefits pharma companies on the financial side, but just in general across the industry, it’s a race. On our side, that means that we are trying to come up with processes that make everything more integrated and easier for the client.

How do these challenges affect biomaterials development and delivery? Are they widely similar or are there other knock-on effects that need to be considered?

DW: The challenge is similar. The big issue in terms of biomaterials is that the regulatory environment is very complex and dynamic so cell therapy manufacturers and drug manufacturers want to be confident that we are doing things appropriately and being guided through the regulatory pathways. They really need to know that what we’re doing on the biomaterials end is completely streamlined, but you also have to follow the rules. Being a part of Versiti Blood Centre, we live and breathe in the regulatory environment. We bring lifesaving blood products to patients 24/7 and are bringing that background and experience to handling biomaterials, too.

How have clinical trials been affected by Covid-19, and what have you done or are you doing to overcome either exacerbated or novel challenges?

BH: If Covid-19 has taught us anything, it’s to expect the unexpected and just to be prepared. I think we saw a big shift in the way clinical trials were run during Covid-19 and there were lots of issues from the supply side, the FDA even issued some guidance about decentralising supply chain.

For clinical trials in general, we saw a shift from patients being seen at doctors’ offices to being seen at home. With a lot of home visits as opposed to doctor’s office visits, the supply chain supply chain was one of the biggest problems that we ran into.

More generally, the supplies that were needed for clinical trials or other projects changed drastically. For one client where we would usually manufacture 100,000 tubes of a molecular transport medium, we found ourselves manufacturing ~8 million from March/April 2020 through to January 2021. This was a huge scale up for us personnel-wise, manufacturing-wise, clinical trial-wise, trying to keep our staff safe.

We run a lot of oncology and infectious disease trials so we couldn’t not be in the office or the lab. We therefore had to find ways of doing this safely, and also pivoting our business model a little bit. For example, we were very clinical trial-heavy at one point and moved over to manufacturing when the clinical trial piece slowed down because they couldn’t see patients. So I think that the biggest change was trying to overcome staffing and really just supply chain in general.

How did you collaborate with people who were perhaps outside the typical or expected sphere of potential partners?

BH: During the project I described above, where we were manufacturing molecular transport medium cryovials, the vials that were typically used to store this medium weren’t available. They came from overseas, you couldn’t get them in, there were huge delays in having them manufactured and we saw Coca Cola step in to help with manufacturing. So if you can imagine their 20-ounce Coca Cola bottles before they were blown up into the actual bottle itself, these are called preforms. These were small tubes with great seals, and we were able to obtain millions of them so that they could be used for the testing of Covid-19.

How about with biomaterials provisions – have there been any unique opportunities for innovation here?

DW: During the pandemic, we had very limited access to traditional methods for recruiting and collecting donors. Typically, with blood centres, a lot of the time they’re going out to the donor and going to universities and high schools, which can count for 20-30% of the donor base. During the pandemic, those were closed or they were virtual and so we had to go back to a more traditional recruitment process where the donors come to our fixed sites with apheresis technology and the safe recess technology we use.

Every day we’re collecting stem cells for therapeutics. We can recruit – which is something that that we really know how to do – and then build this pedigree donor base and be able to perform all types of testing because we have our own infectious disease testing laboratory.

We can also do HLA typing among many other types of testing which means that not only do we have a large and expansive donor base, it is also highly differentiated.

So we’ve really learned over the last few years how to bring people to us and how to do it in a safe and regulated.

What has it been like to scale up clinical trial operations in the midst of a pandemic?

BH: If I said it was easy, I would be a liar. I’ve been in clinical trials for well over 20 years and it’s been one of the most difficult things I’ve ever had to do, and really more on the supply side than anything else because it’s just not something you could have expected.

We’ve been very fortunate to be able to bring in enough supplies and have them available at any time, but we really had to revamp our systems internally for the supply chain and making sure you have supplies for these clinical trials.

Pre Covid-19, you needed to look out a month or two, but what we’ve learned during Covid-19 is that we have to look out six, eight, even 10 months predict what the usage is going to be because sometimes it’s taking six to eight months to get these supplies, so we had to redesign our systems to be able to look out that far. We also had to think about labour as well, making sure we have enough people in the lab to manage demand.

The other thing we have seen is that clinical trials were put on hold for a short period of time because of Covid-19, and now everybody wants to start back up. Well, when that happens, you better be ready for it, and so we had to make sure that we had staff in place who were trained and ready to go when everything restarted.

How does this compare to the scaling up of biomaterials over this time?

DW: One thing that we’re really working on is becoming very vertically integrated so that we have a ‘one-stop-shop’. We’ve had this for decades as a business in terms of blood, blood products, and now getting into biomaterials.

We’ve had to consider, how do we bring it into our supply chain where we have a research institute, for example. We have worked with a number of IRB-approved protocols with many different protocols and different entities with a highly characterised donor base, and we know that people can come to us and say, OK, we need this and we need it in this time frame.

Another thing we have had to consider is that a donor may need to be on an apheresis device for a number of hours, and so we have had to consider, how do you give that donor of a good experience so that they want to stay in your program? And so a lot of the work we have been doing is customer service, making sure donors will come back and advocate to others to join our programs.

A lot of what we’ve covered today relates to innovation, so where have you seen the strongest demand for innovation within your respective areas and what has this meant for your area of expertise?

BH: So for clinical trials I would say, flexibility and nimbleness – being able to pivot and turn on a dime –  and I think that’s what we’ve seen because of the pandemic as we didn’t know what to expect.

During the pandemic, some clinical trials continued, especially within oncology. When we then started to see new guidance about testing for Covid-19 antibodies, we then needed to think about how we were going to manage that and how we were going to collect those samples, get them tested, collect the results and how we were going to do it all in a rapid timeline. We couldn’t wait for 6 weeks, we needed those supplies within a week.

However, all of a sudden these patients couldn’t travel anymore. Doctor’s offices were shut down, so then how could we care for those patients? How do we collect those samples? How do we monitor those patients? How do we make sure that they’re safe while they’re on the drug? The challenge then was not just come up with a way to do it, but to come up with a way to do it yesterday! I think that was the biggest thing that our clients were looking for.

DW: And talk to batsman for the biomaterial side, as new research is going on and therapeutics are being developed, companies are really looking for very highly characterised, very specific types of donors and materials, and so you need to have a donor base that that you can go to. You can’t just go out and recruit donors for single, specific projects.

What we’re doing day by day is recruiting donors, performing a lot of characterisation and testing, and then really looking at analysing them, which allows us to build a donor base that is robust and ready to go, but it was challenging during the pandemic considering how to recruit donors and then perform the testing methodology.

We do have our own donor or viral testing lab and so we can do all this testing within our own facility which means we can perform the characterisation testing ourselves, and further means we can manage a project from the start all the way through to the end.

Finally, what do you see for the future of biomaterials and clinical trial delivery? What are the obstacles that remain and what are you doing to mitigate or overcome these challenges?

DW: I think we’re really building that ‘one-stop-shop’ where an organisation, company or research lab can come to us and say, ‘this is what we need’ and for us to be able to say, ‘OK, we can handle this’. We are able to get the biomaterials we can, manage the project and make it very specific.

From this, we can develop very targeted types of therapies and really be able to get the pharma-grade products with the right approvals and set-up for clinical development.

BH: For clinical trials, I think the changes that we’ve seen over the last year are probably here to stay. I think we’ve all experienced that in the workplace. I think a lot of the changes we’ve seen where we were protecting ourselves from supply chain issues where we are seeing patients at home, we’re having to figure out ways to do that where we’re having to pivot and seek studies constantly change. I think that flexibility is here to stay.

This feature has been produced in partnership with Versiti