Author: Senija Selimovic-Hamza, Márcia Costa Edited by: Jun Hon Pang
The field of cell and gene therapy has seen tremendous progress and promises to treat a wide range of diseases, most notably genetic diseases and cancer. However, commercialization of such technologies from bed to bedside faces challenges particularly in manufacturing processes, logistics as well as regulation. Here, we interviewed two prominent professionals with expertise in supporting translation of such therapies:
(i) Dr. Bo Kara from GlaxoSmithKline (GSK), an expert on the process development of such therapies
(ii) Dr. Jacqueline Barry from Cell and Gene Therapy (CGT) Catapult, who has significant experience in the quality and regulatory aspects.
Both of them will be speaking in the upcoming SIULondon’s flagship event ‘Advances in immunotherapy: Innovations from the frontline’ on 2th May 2018.
Dr. Bo Kara, GSK
Dr. Bo Kara is the Head of Process Development of Cell and Gene Therapy Platform Chemistry, Manufacturing and Controls (CMC) at GSK. Dr. Kara leads the development of manufacturing processes for GSK’s cell gene therapy vector and autologous cell processing platforms. He possesses almost 30 years of experience in development of scalable manufacturing processes for biologics products, with knowledge of the technical, regulatory and commercial issues faced at each stage of the manufacturing process development. He is a primary inventor on a range of process and stem cell patents.
Throughout the years you have built up an impressive CV by working for companies such as Astra Zeneca, Fujifilm Diosynth Biotechnologies and now GSK. What has led you to take on the position at GSK?
I have been involved in biologics development and manufacturing for a significant number of years, focusing on protein therapeutics from the evolution of biologics as products. Back then, there were no biologics products such as recombinant antibodies or proteins on the market, and I got involved in the early days of growth of the technology and as the market increased. In my later years at Fujifilm, I had started looking into the bioprocessing of stem-cell therapies. When the opportunity for this role at GSK came along, I joined as I thought that it was an exciting opportunity to get involved in an area, which was at an early phase of development with lots of challenges. Another key factor for me was that cell and gene therapy is probably the closest that you can get to a patient from my area, which is process development CMC. Each product that we manufacture is for one patient, so that was the opportunity to contribute and make a difference, especially to individual patients.
What would a typical day as the Head of Process Development look like?
Other than battling with Skype, my primary role is to lead the process development activities to deliver our manufacturing platforms for our assets. I have technical teams involved in areas such as upstream and downstream development and process engineering. My job is to lead and guide the direction of the work so that we deliver industrialized manufacturing platforms for our viral vectors. In a typical day, I deal with technical work like looking at goals, updates, data reviews and future work. The other focus is the CMC, for which I look across projects. A lot of my time is spent in matrix meetings where we look at overall strategy to deliver the ‘medicine’ now into clinical development and longer term into commercial supply. As the head of the group, I’m unfortunately not a hands-on scientist anymore, which is a shame, but I do get to see the data and the ‘story’ as it evolves because it’s a science and data driven role.
While we know that academia cannot offer enough jobs for young scientists, many of them still have troubles deciding for industry. What advice would you give them?
Obviously, I am biased and my job is to attract and coach the best scientists from wherever they are: academia or industry. I just want to emphasize that folks in academia should not view the industry as “not doing science”. I think there is a misconception in academia that science happens in academia but does not happen in industry. My view is that the quality of science is the same - everyone is doing great science. I think the only difference is the focus. In industry, particularly in process development, we are application focused, as data and knowledge is gathered we can change our direction quite quickly. In academia you can often continue and learn something new and add to the knowledge base. In industry, if we are not delivering we can stop a particular direction, implement back-up plans or think of something completely different, but what we do is still high quality science. So, my first message to people in academia would be to not have a misconception about what happens in industry. My second message would be ‘Don’t not consider industry. Find out about what we do and the roles and career development we offer, and see if it lines up with your interests.’ Just to reiterate, I personally don’t see a difference in the quality of science, I just see a difference in the type of science.
What innovations and advances in cell culture process development would you like to see in the next ten years?
In my opinion, in five to ten years time we will understand viral vectors much better than we do now, we will be generating viral vectors of higher quality and we will be delivering viral vectors in autologous cell therapies where the cost of goods is something that is no longer an issue. In ten years from now, there will be a mix of autologous products, some using viral vectors as a manufacturing system and some utilizing direct gene editing as a manufacturing system. But ten years is a long time. I wouldn’t want to wait ten years to see advances in the area. My view is that we can exploit the lessons learnt about the biologics industry from both academia and industry to accelerate the development of viral vector manufacturing. We don’t need to wait ten years to get there. For me it is more about developments that are happening faster.
What can we expect from your presentation at the SIULondon ‘Advances in Immunotherapy’ event on 2th May? Who will it benefit?
My intention is to give a view of the direction of where the challenges are in viral vector manufacturing, and an indication of how we at GSK are addressing some of the challenges. I hope to give people a view of what we are trying to do, where we see the challenges and what our strategy is. We are a multidisciplinary team, so I do hope that the audience is also multidisciplinary because there’s a role for each discipline while working towards the end goal. It might be useful for cell culture scientists, process engineers, downstream scientists, etc.
Dr. Jacqueline Barry from CGT Catapult
Dr. Jacqueline Barry is currently the Chief Clinical Officer in CGT Catapult, which is a centre of excellence in providing regulatory help to researchers to make their newly developed cell and gene therapies commercially available. Dr. Barry started her career as an academic researcher studying neuromuscular regeneration. She then worked at the Scottish National Blood Transfusion Service in multiple quality and regulatory positions. She possesses experiences in the development, translation, clinical trial and approval of cell based therapies.
You started your career in academia, then moved to regulatory affairs. What led you to make that move in your career?
My career in academia was neuroscience and I really liked it, but I felt it was just too far away from clinical translation. I wanted to go somewhere where I could actually see where there would be a direct use (of the therapies) to patients. That was the main reason why I went to work with a blood transfusion service, where it’s very donor and patient focused. It was not because I disliked academia like some people do, it was just that it was not giving me everything I wanted for my career.
How was your transition to your current position at CGT Catapult? What does that entail and how’s your daily job routine?
Obviously moving from academia, there is a different pressure on you, especially when you move to the NHS. It was a challenge to move to a totally new environment, but I really enjoyed it, once I became used to using Standard Operating Procedures (SOPs) and working within a regulated environment and indeed I could see all their benefits. I started with plasma products, and subsequently moved to blood and tissues and cell therapies. I moved from there to Cell and Gene Catapult. Now a work day, oh my goodness, is a long day, and each day is different because we deal with many projects and have been involved in over 80 projects in 5 years since CGT Catapult was set up. These complex projects are at the forefront of technologies, so one has to keep up with the evolving science, which is both interesting and challenging. We also do a lot of engagement activities, where we interact with the regulators, government, trade bodies and other international bodies. I manage a team of about 33 people, which includes specialists in the field of cell and gene therapy field in regulatory affairs, nonclinical and clinical operations and programme management - so it is multi-faceted.
What is the main mission of CGT Catapult and why is it important to regulate this type of therapy?
Catapult is now well known and its role is to grow the cell and gene therapy industry in the UK. We received our funding from Innovate UK. In terms of the regulatory requirements, because this is a really new discipline, we are still understanding the science and the clinical implications. For example, CAR T-cells have a tremendous therapeutic value, but there is also an acute and serious clinical risk with them. Thus, they have to be regulated because they are very potent medicines. There are also other considerations, because you are taking cells or tissues from a patient or a donor, manipulating them for example with gene therapy, and then injecting them back with genetic modifications to the same or a new patient, so it is a very complicated regulatory pathway.
What advice would you give for researchers that are developing new cell and gene therapy techniques to see their ideas approved?
This is going to sound trivial, but plan early and understand early. Seek the long game. A really simple example might be stability trials for the material you’re using, which quite often academics forget. Product, which may otherwise be disposed of, can be retained and then retested at predetermined times to determine the stability of the product the developers is producing. Another example may be to think about the future development of the product because changes made earlier which could reduce the cost of manufacture of the product, or a targeted clinical path based on health economics and with reimbursement in mind then this shows a maturity of thought by the developer which is and hopefully more attractive to investors and funding bodies.
We are all looking forward to hearing more from your presentation at our upcoming ‘Advances in Immunotherapy’ event. Can you give us a sneak peak of what we can expect from your talk?
To help scientists who are looking to get their therapies approved or commercialized, I will be talking about innovation and adoption of therapies as I think it would be most informative, so I will show some success stories and what the next steps for clinical trials are. I will give some local, i.e. UK, examples.