02UQ8YCGA Cell & Gene Therapy Manufacturing & Commercialization US Post Event Report personalized
We gather highlights from Cell and Gene Therapy Manufacturing & Commercialization US 2021 in its first time as a hybrid conference.
Cell & Gene Therapy Manufacturing & Commercialization US 2021
Post-event Report
In September 2021, Cell and Gene Therapy Manufacturing & Commercialization US returned for the first time as a hybrid conference.
Co-located with BioProcess International, the event spanned across seven days, welcoming audiences in Boston and online, with tracks exploring:
- Cell Therapy
- Gene Edited Ex Vivo Cell Therapy
- In Vivo Gene Therapy
- Partnering & Collaborations
- Tissue Engineering
In this post-event report in association with Avantor, we gather a collection of highlights from the week, including top presentations, a key panel discussion, poster and a spotlight session to watch on demand.
Jump to any article using the contents on the following page, or at any time using the Contents menu in the top left. There you can also download this report as a PDF.
COVID hit cell and gene therapy trials and suppliers but experts see signs of recovery
Industry leaders discuss the state of supply chains and clinical trials in the aftermath of the pandemic
COVID hit cell and gene therapy trials and suppliers but experts see signs of recovery
Freelance business and science journalist Gareth Macdonald picks key takeaways from BPI Magazine's State of the Industry Webcast.
COVID-19 disrupted cell and gene therapy trials as well as the contractors and suppliers that support them according to experts.
SARS-CoV-2, the virus that causes COVID-19, impacted all parts of biopharma. For example, the focus on vaccines highlighted manufacturing capacity limitations while increased demand for consumables and raw materials put pressure on suppliers.
The pandemic also disrupted R&D to the extent that some developers put projects on hold according to Amelie Boulais, head of market entry strategy at Sartorius, who told attendees at the BPI virtual conference that the problems fed back up the supply chain.
“The entire supply chain for the industry has been stretched by the pandemic…we try to mitigate any risk of shortages or unanticipated disruptions, we monitor our stock levels during daily operations.
“But all our strategies rely on forecasts from our customers and, with COVID, suddenly, some customers working, for example, in the gene therapy field, just stopped production because the trials were on hold.”
The disruption of supply chains had less of an impact on the cell therapy industry according to Patrick Lucey, CEO of CDMO Lykan Bioscience.
“We actually have avoided a lot of these delays in the cell therapy space. Obviously, the amount of materials we use is reasonably small scale… we're not looking for major demand of excipients, or media components or buffer components or disposables.
“So we've been able to navigate this in a couple of ways. First, you know, our supply chain team was pretty forward looking. So there are common materials across all biologics manufacturers, cleaning materials, and things like this. So we moved quickly and stockpiled a lot of these cleaning materials and things to be prepared for changeover and all that work.
“And then on the on the client or processing material side, again, cell therapy is reasonably small scale, so not a huge demand for common raw materials, we do use a shared raw material approach across clients, so they have a security of supply there.
But the cell therapy sector has not escaped the disruption, according to Lucey, who told delegates clinical trial activities were impacted.
“Where COVID did impact cell therapy is a lot of these therapies in terms of clinical trials require access to ICU for side effects. And certainly at the peak of COVID we saw ICUs in the US and globally overwhelmed with COVID patients.
“So the availability for the proper resources from that perspective, were constrained, and therefore, clinical trials were delayed,” Lucey said.
"A lot of [cell] therapies in terms of clinical trials require access to ICU for side effects"
Patrick Lucey, CEO, Lykan Bioscience
The positive news is that many trials halted during the early months of the pandemic have resumed. Partly, this is because trial sites have reopened or sponsors have switched to decentralized models. In addition, supply chains have recovered or been modified.
Vectors are an exception according to Lucey, who says that, despite commitments to increase production capacity, sourcing is still a challenge for the cell and gene therapy space.
“The one area that continues to dog the cell and gene therapy segment is really the access to lentiviral, or viral vectors in general. We've seen a lot of capacity go up for viral vector production, but yet we still see some of our clients challenged with sourcing.
“And so that's certainly an area that that's still challenging from a capacity perspective. But otherwise, I think we are we are getting back to normal in the cell therapy side.”
<small>A collaborative ecosystem to accelerate the commercial manufacturing of novel vaccines and other therapeutics
Dr. Nandu Deorkar, VP, Research & Development & Biopharma Production at Avantor presents
A collaborative ecosystem to accelerate the commercial manufacturing of novel vaccines and other therapeutics
This presentation by Dr. Nandu Deorkar, Vice President, Research & Development & Biopharma Production at Avantor, discusses how suppliers and manufacturers can partner to overcome the challenges of drug development related to the scale-up, technology transfer, regulatory considerations, and commercialization timelines of bringing new therapies to market. Watch the full on-demand session or read the overview on the following page.
Over the last 35 years, the biopharmaceutical industry has made significant contributions to improving human health outcomes by developing and commercializing recombinant protein and monoclonal antibody (mAbs) therapies. 2021 marked the FDA’s approval of its 100th mAb therapy while simultaneously, groundbreaking research has resulted in safe and effective nucleic acid and gene therapy platforms.
Innovation in these areas enabled the rapid commercialization of vaccines for COVID-19 and will continue to drive the future of medicine; however, the industry will need to achieve greater efficiencies and scale for its manufacturing and supply chain processes for innovation to continue to translate to successful, sustainable commercialization.
About the Speaker
Dr. Nandu Deorkar is Vice President, Research & Development & Biopharma Production at Avantor. During his more than 25-year career in materials technology research & development, Dr Deorkar has worked on various aspects of chemical/polymer R&D, drug development, formulation, drug delivery technologies, process development, and technology transfer.
Dr Deorkar earned his PhD in chemistry from the Indian Institute of Technology, Bombay, and his MBA from Fairleigh Dickinson University, New Jersey (USA).
Quality gene therapies require quality analytics says expert
Release testing, process development and platform methods: Biomarin Pharmaceutical's Lyndi Rice explains key analytical considerations for gene therapies
Quality gene therapies require quality analytics says expert
Gene therapy quality depends on choosing the right analytical methods and technologies for each part of the production process says an expert.
Lyndi Rice, head of the QC viral vector analytical group at Biomarin Pharmaceutical, told delegates at the BPI virtual conference “Analytics are really critical from the start of the manufacturing process and all the way to the end of product testing and monitoring.
“Release testing is critical for measuring product quality by assessing its identity strength, purity and safety.
"And stability methods measure the stability of the product under different conditions as well as over time and can help to inform shelf life for your product.”
The key to an effective analytics strategy is ensuring the correct methods are used as each part of the development and production process Rice said.
“It is important to ensure that the method performs as well as needed to monitor the manufacturing process at each of those steps.
She also said information needs to be gathered at all stages of production, explaining “It's important to collect data, especially early on in product development.
"These results can be leveraged during investigations to understand how product quality might have been affected, should there have been anything that maybe was a little bit off during the manufacturing process.”
Incorporating analytical systems into process development – even manufacturing facility design – is the ideal approach as it ensure that the desired critical quality attributes can be monitored effectively.
However, companies also need to consider the use of alternative methods according to Rice, who urged gene therapy producers to ensure a degree of flexibility in process and facility design.
“It is very important to thoughtfully design your analytical suites to be sure that they're measuring these attributes appropriately. And it is potential that orthogonal approaches may also be required to measure some of these attributes.”
Gene therapies have complex mechanism of action and it is critical that developers make sure that any therapeutic impact is due to the products itself rather than variation occurring during the manufacturing processes.
Analytical technologies are key to minimizing batch to batch variation and ensuring gene therapies are consistent, Rice said.
“Gene therapy products are known to be complex, heterogeneous and have complex mechanisms of action. Product characterization is therefore critical to ensure product safety as well as to demonstrate batch to batch consistency over time, and to help you interpret your clinical study outcomes.
“Robust analytical methods are therefore required for sufficient product characterization. And you can also consider during product development phase appropriate analytical method development.
"So by phase three pivotal trials, it is expected that you would have all of your methods validated.”
Again it is critical to select the appropriate analytic method and to ensure it is providing the information needed at each stage of the process Rice said.
“You can refine your methods as product knowledge increases, and focus on method robustness, accuracy and precision early, especially for your critical methods such as dosing and potency. And this is because you're going to be making really important decisions based on method performance and those method results.”
“So you should really focus on these methods early on in product development. Platform methods can also help to save time and resources without sacrificing quality, but they do require that your manufacturing process is also somewhat platform.”
For gene therapies manufactured using more novel processes such a platform focused approach may not be as effective. In such circumstances, firms should consider a” quality by design or QBD approach for analytical method development.”
From 50 million to 15 billion human iPS cells within a week
A poster by Anthony Renodon, Business Development Officer, Treefrog Therapeutics
From 50 million to 15 billion human iPS cells within a week: Highly reproducible exponential iPS expansion in 10l bioreactors with maintenance of cell quality
by Anthony Renodon, Business Development Officer, Treefrog Therapeutics
2D cell culture has been widely used to manufacture the first generation of cell therapies.
However, due to the drawbacks of scale-out processes (footprint, workforce use, variability and subsequent QC expenses), the industry is shifting towards the gold-standard for bioproduction scale-up, i.e. bioreactors, with the goal of addressing mass-markets with standardized and affordable products.
Here using new C-Stemâ technology based on a high-speed cell encapsulation microfluidics, we report the production of two single batches of 15 billion hiPSCs in 10L bioreactors with an unprecedented 276-fold amplification within a week.
Data demonstrates high-reproducibility and maintenance of best-in-class cell viability and pluripotency.
Also documenting the scale-independent amplification profile obtained with C-Stemâ in 30mL, 500mL, 1.5L and 10L bioreactors, we argue that the C-Stemâ technology is amenable to produce commercial-size batches of stem cells in larger bioreactors.
Click to the next page to view the poster >>>
<<<< Click to expand >>>>
Room for allogeneic and autologous product in the cell therapy space, says panel
Industry experts discuss whether autologous or allogeneic therapies could coexist in the industry
Room for allogeneic and autologous product in the cell therapy space says panel
Allogeneic products may dominate the cell therapy sector thanks to tech and cost advantages but there will always be room for autologous treatments, say experts.
Cell therapies are either allogenic – derived from a universal donor – or patient-specific, autologous products. The products treat disease in the same way, what differs is the types of immune responses they generate and the process used to make them.
And – according to a panel of experts at BPI – these differences that will ultimately will shape the development of the cell therapy market.
RoosterBio founder Jon Rowley told attendees “I do believe that they [allogenic and autologous therapies] are going to coexist, at least for the next 20 plus years.
"One of two things is going to happen: either our genetic engineering of cells or the body will allow us to reduce any immune rejection of allogenic cells.”
“Also, the allogeneic cost structure hands down beats autologous, so I think that the allogeneic model will win out, but, it's going to take like 20 or more years.”
A less likely possibility Rowley says is that the cost of making autologous therapies – which is usually higher than for making allogenic products because of their patient-specific nature – is reduced.
“It is also just as possible that the supply chain really get worked out of the autologous model to the point that the difference in cost isn't going to matter.”
In such circumstances physicians and payors may favor the immunological and potency benefits of “self-products.”
This view was echoed by Armon Sharei, SQZ Biotechnologies CEO, who said “There's two problems to be conscious of with cell therapies. There's the biology side, and then the manufacturing and logistic side of it.
“From a manufacturing and logistics perspective I think we would all agree allogeneic will always be faster and cheaper and from an accessibility standpoint than an autologous one could be. So it comes down to, on the biology side, how often would autologous be superior?
“And I think for many things, oftentimes, the auto will always be better biologically, because you don't have to worry about the donor cells reacting to your body, or your body reacting to the donor cells. And there's a lot more biological flexibility on what you could pursue with an autologous therapy.
“So I think that's where auto will always exist, and then allo to the extent possible for a certain cell therapy could be the kind of off the shelf alternative for it” Sharei added.
Sharei also suggested growth of the point-of-care treatments – in which the product is prepare or partly manufactured at the clinic – would impact the balance of cell therapy market by improving access.
“Squeeze is working towards a point of care version of our system where you can make autologous cell therapies available on site. And if you can get to that point, with certain autologous therapies, you may kind of stop caring, whether it is allo or auto from a manufacturing, logistics standpoint in biology alone will be what matters.
"Auto will always be better biologically, because you don't have to worry about the donor cells reacting to your body, or your body reacting to the donor cells"
Armon Sharei, CEO, SQZ Biotechnologies
“So in the end of the day, like at Squeeze, you know, we don't fundamentally care about auto versus aloe, but biologically, I think auto would tend to be the superior one, but you would do aloe if the biology allowed you to do it.”
Cenk Suman, Chief Technology Officer at Stemson Therapeutics, voiced a similar opinion, telling delegates that while there is room for both types of cell therapy at present but cost is a constraint for patient-specific products.
“We have to really consider making autologous, much more cost effective. And I like the idea of production by the bedside, essentially on site manufacturing… At Stemson. We are considering both autologous and allo.”
For Ali Mohamed, vice president of CMC at Immatics Biotechnologies, the question is about the number of doses required.
“My concern about allo is that you are spreading the cells too thin, too much expansion. So you're losing steam as you go. it's a delicate balance to say, why am I trying to get away from autologous because: A, the patient salts are already cooked and they're not suitable for cell therapy; B it's going to cost me a lot of money to make a single lot from one patient to one patient.
“But the problem that you're going to face with the allo is how much can you expand? You're not going to get 500 doses out of one donor, you're probably going to get 10 and potentially less and you may have to multi-dose because sooner or later these cells are going to get rejected.
“So at the end of the day… autologous is definitely the king. I think with some help and some development allergenic cells can catch up especially if it's the right paradigm, the cells are expanded in a way not to lose their way not to lose their memory phenotype.
“So 10 maybe 20 years from now we'll say allogeneic are better. But as of today, autologous cells are better,” Mohamed said.
