Apparently, quite a lot. At the Informa 2016 Cell Therapy Manufacturing & Gene Therapy Congress in Brussels in February, 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, UK, a “second- generation” CAR-T immunotherapy company that spun out from University College of 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.” Jim Faulkner’s point (full name given to avoid literary reference confusion with William) 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 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 passing people who added features. Now, a customised Range Rover is created every 68 seconds and that factory conveyor belt is completely roboticized.
If even the Queen of England embraces the benefits of an industrialized era as drives around her estates in a Range Rover, then surely it is high time for the cell therapy industry to modernize the lab. 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 media.
A series of these innovative solutions, often developed the hard way, were shared at the conference. Many advised to consider these design issues early. Nasser Sadr, who is Manager PD&R at PharmaCell BV in the Netherlands, discussed how even the layout of the facilities were renovated to better service a “high through-put” autologous production pipeline that needs more open, shared space rather than compartmentalisation 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 wanted a better product design. By combining computer programming with science, it created a Boolean-like technology it refers to as “Logic Gates” that increase recognition capability to target multiple cancer antigens.
Let’s hope the next literary analogy at the Informa 2016 conference is Odysseus’ return to Ithaca after 20 years of wanderings rather than Alice freefalling down the rabbit hole. It may have taken some time to build the know-how and tools to get there but cell manufacting has been an epic journey trying out different “cultures” and ideas. At long last, largescale efficient and quality cell manufacturing appears to be on the horizon and is due its homecoming soon.
By James Smith & MacKenna Roberts – Reposted here with permission of Signals (www.signalsblog.ca)