A case study following the adoption of BeadReady™ for the room temperature shipment of cell therapies in India
by Steve Swioklo, Senior Scientist and Co-founder
It was the 20th April 2017 when I first visited Hyderabad, to attend a workshop hosted by the L.V. Prasad Eye Institute (LVPEI). This was an initiative supported by the British Council and Royal Society for Chemistry aimed at finding novel solutions to confront problems associated with sight loss following damage to the cornea, the transparent window at the front of the eye. I was soon introduced to the magnitude of the problem in India, with 5 to 6 million people suffering from blindness in one eye, and 1.2 million people with both eyes affected. Sadly, this incidence is still growing with up to 30,000 new cases being added every year and a large number of these being children less than 6 years of age. Prompt and proper treatment of corneal damage is necessary to prevent blindness. This is a major aim of the LVPEI, the largest eye care network in India. It is a not-for profit eye care institution committed to delivering high-quality treatment and care for patients, embracing all socio-economic backgrounds. Their motto is “So that all may see” and in evidence of this, they have treated 24 million people over the last 30 years, with more than half of the service provided free of charge.
Shelf life of 6-8 hours
On my second day there, Dr Vivek Singh from LVPEI presented some really exciting clinical trial data that described the use of stem/stromal cells that are taken from cadaveric corneas, cultured in a cGMP facility, and implanted back into the eyes of patients with corneal damage. The trial, based on years of multinational research, represented a potential solution to prevent or reverse corneal scarring and subsequent sight loss. This opportunity came with a problem. Once the cells were ready for implantation, they only had a shelf life of 6-8 hours. This allowed the treatment to be available at their centre of excellence, where it is manufactured, but impeded its accessibility to those patients in remote rural areas that needed it the most. Either: (i) the cells had to be transported to clinics in these remote areas, or (ii) the patients would have to travel to their main centre in Hyderabad. With a shelf life of hours, the first of these options would not be possible. They could freeze the cells and transport them frozen, but the complex costly infrastructure for cryologistics is not feasible and the cell viability and function of cells post-thaw would likely be compromised. The second of these options was also not possible. It is often the poorest of people that need to access the therapy and they simply can’t get themselves to Hyderabad for treatment; where speed of treatment maximises the therapeutic outcome, this had major disadvantages. In order to maximise accessibility “So that all may see” the shelf life of the fresh product needed extending.
This is where we came in. I was attending the workshop as a post-doc with my PI Prof. Che Connon. A major part of my research was focussed on the development of an alginate hydrogel-based technology that preserved cells at room temperature to allow their storage and shipment for multiple applications. At the time, we were in the process of translating this University-born research into a commercial opportunity and were in the process of starting a company with myself, Che and Dr. Mick McLean. Atelerix, was incorporated less than 2 months after this opportune meeting in Hyderabad. Discussions continued after our return to the U.K. and we developed a plan. The prospects seemed exciting!
15-fold extension to shelf life
By January 2018, I was back in Hyderabad. The visit, supported by the Department for International Trade, aimed to evaluate the capacity for our technology to preserve LVPEI’s therapeutic cells at room temperature using a simple process of cell encapsulation that we now call BeadReady™. I worked in the cGMP manufacturing facility to conduct this process, accompanied by Mukesh Damala from the LVPEI. Everything went to plan and the cells were placed into storage. We then had to wait for 3 days before the first time-point for cell recovery. This day arrived and within minutes gels were dissolved, cells were recovered and ready to count. These cells that previously had a shelf life of hours were now recovered with high viability, yield and function after days! Similar results were seen after 5 days of storage, a 15-fold extension to shelf life. It was clear how much impact this technology could have and the simplicity of the process demonstrated how easily it could be adapted to clinical use.
Extreme Indian Summer temperatures
In a way, that was the easy bit done. These were the results that we expected to see! Next we had to test whether cells remained alive when transported through the busy roads of Hyderabad in extreme Indian Summer temperatures. Over the course of months, cells were repeatedly encapsulated by Mukesh, packed into shipping boxes and driven around India. Ambient temperatures reached up to 38 degrees Celsius, but the cells still survived! The potential to now use BeadReady™ to stabilise this new cell-based therapy with maximal accessibility and reach was now reality. In November 2019, this work was published as an article in Scientific Reports and BeadReady™ is expected to enter clinical trials later this year.