Post by James Smith and Mackenna Roberts. Ms. Roberts is an English-qualified lawyer, trained bioethicist and strategic adviser for the commercialization of emerging biomedical technologies and is widely published on how the law should govern cutting-edge medical therapies. She is an associate at IP Asset Partnership Ltd in London, IP consultant to IP Asset Ventures and adviser to the Centre for the Advancement of Sustainable Medical Innovation (CASMI), a European initiative aimed at accelerating more affordable therapies to patients. Ms. Roberts holds a Masters in Medical Law and Ethics from King’s College London.
If you attended the Informa 2016 Cell Therapy Manufacturing & Gene Therapy Congress in Brussels in February, you’d think “quite a lot.” Day 2 was replete with pertinent analogies that provided inspiration and advice on how to approach pervasive design and manufacture issues relating to cell therapies.
Jim Faulkner, Head of manufacturing at Autolus, a “second-generation” CAR-T immunotherapy company that spun out from University College London (UCL), found industry wisdom in the words of Lewis Carroll’s the Cheshire Cat who asks the lost Alice in Wonderland where she wants to go. After she replies that she does not care, the Cat quips, “Then it doesn’t matter which way you go.” Dr. Faulkner’s point was that if you do not know what product you are designing, then it is difficult to design.
It may sound obvious, but retaining a simple vision of the end product when so many possibilities exist – not only when tackling the multifactorial and complex immune system, but also involved with using and processing living biomaterials such as cells – means the direction the product design and manufacture should take is anything but straightforward. So amidst the fray of choice to assemble and innovate an optimum (T cell) therapy, a simple guiding principle to keep in mind – whether from experienced industry veterans or the Cheshire Cat – is certainly welcome.
While those in the cell therapy field may identify with Alice feeling lost and bewildered at times, it is clear that what the cell therapy story has most in common with the novel is creativity. Ohad Karnieli, who is on the Process and Product Committee of the ISCT and Co-founder & CTO of his own company, Karnieli Ltd, compared cell therapy manufacturing to the car industry. He showed a picture of cars on a conveyor belt and workers adding features. These days, a customized Range Rover is created every 68 seconds and that factory conveyor belt is completely automated.
If even the Queen of England embraces the benefits of an industrialized era as she drives around her estates in a Range Rover, then surely it is high time for the cell therapy industry to modernize the lab. Dr. Karnieli acknowledged that mere automation of cell manufacturing will not help these promising therapies reach as many patients as possible. The car analogy falls short.
So up flashes a picture of operators manually connecting telephone calls at an old-fashioned switchboard. Automation alone did not elevate the benefits of Alexander Graham Bell’s discovery of the telephone to its full potential. Bell likely could not have conceived of the iPhone. Cell therapy will need both automation and innovation to achieve its full potential.
Karnieli walked through a series of innovative lab equipment design changes he implemented and many were simple DIY steps others could easily follow. For example, he eliminated the need for manually hanging and switching cell culture bags and reconfigured them so the manual valves, which caused imprecise amounts of solution to be added, became mechanically controlled.
He achieved impressive uniform results for his makeover efforts. The consistency of his results better allowed him to isolate and evaluate single variables such as which serum-free solution is the best medium. A series of these innovative solutions, often developed the hard way, was shared at the conference.
There was also lots of advice to consider these design issues early. Nasser Sadr, who is Manager Process Development and Research at PharmaCell BV, discussed how even the layout of their facilities were renovated to better service a “high through-put” autologous production pipeline that needs more open, shared space rather than compartmentalization for “scale-out” allogeneic production.
For Autolus, a single antigen approach to CAR-T construction limits the number of cancer tumors that can be targeted and it needed a better product design. By combining computer programming with science, Autolus created a Boolean-like technology it refers to as “Logic Gates” that increases recognition capability to target multiple cancer antigens.
Let’s hope the next literary analogy, at the Informa 2017 conference, is the homecoming scene from Homer’s Odyssey rather than a lost girl freefalling down a rabbit hole trying to makes sense of an alternate world. After being lost at sea for 20 years, Odysseus, by sheer force of will and determination, reaches his desired destination: Ithaca.
It may have taken some time to build the know-how and tools to get there, but cell manufacturing has been an epic journey trying different “cultures” and ideas. At long last, large-scale efficient and quality cell manufacturing appears to be on the horizon and is due its homecoming soon.
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