A summary of the excellent meeting hosted by LRMN and Thermo Fisher Scientific, on scalable manufacturing of cell therapies
Yesterday’s LRMN meeting held three wonderful, engaging talks by experts in regenerative medicine. Sadly Myriam Jordan (Thermo Fisher Scientific) was unable to present as originally planned, so Alun Fowler (Thermo Fisher Scientific) stepped up to carry out the welcome instead.
‘One-stop-shop’ at MHRA
Dr Alun Fowler and Emily Culme-Seymour (LRMN) introduced the theme of the talk, ‘Scalable manufacturing and cell therapies’, and thanked the sponsor, Thermo (who handed out goodie bags — lovely!), but then Ian Rees of the MHRA surprised us with a talk about the on-stop-shop that the MHRA has generated to address the issue of the difficulty new or start-up companies have in getting easily accessible, consistent regulatory advice, as indicated by the 2013—2014 House of Lord Science and Technology Committee report. It opened on 13th October this year and will provide a single point of access from the four regulators in the field, the Human Tissue Authority (HTA), the Human Fertilisation and Embryology Authority (HFEA), Health Research Authority (HRA) and the Medicines and Healthcare products Regulatory Agency (MHRA), who will provide a single, coordinated, free regulatory advice service. This cross-regulatory counsel will hopefully have a massive impact for ATMPs, cell therapies and regenerative medicines.
The industrialisation of stem cell production
Next, we heard a lively talk from Aidan Courtney (Roslin Cells Ltd) on ‘The industrialisation of stem cell production’ that flew across the ages, drawing comparisons with previous industrialization and progress in other fields, and making predictions on the future. He stated that over the next few years, lots of small steps development or processes with large steps in imagination would result in reduced cost of cell manufacture and massive progress in the field. He believed that by 2034 there would be an industrialized process for iPSC production, which should be accelerated by the EBiSC project, and also that the gap between clinical- and research-grade cell lines would lessen in future.
Aidan stated that key steps by 2020 would be proteins and small molecules being used as footprint-free technology, the ability to use less-invasive samples, use of more stable, consistent and cheap reagents that are chemically defined, and development of automated, rapid, in-line QC tests.
Predicting the future use of the millions of research-grade cell lines he believed would soon exist, he stated they would mainly be used as a disease model when taken from diseased donors, and to select the best available drug for severe genetic conditions — I have a habit of getting excited by the direct therapeutic applications for cell therapies, so I enjoyed being reminded of the other applications of the technology.
Aidan concluded that the iPSC was the “transistor of our era” — a game-changing technology. In the Q&A session he did cause a stir by stating that the biggest limiting factor was mainly recruitment rather than technology, regulation or funding.
Maturing adherent cell therapies for commercialisation: strategy, technology barriers and possible solution
Next we heard from Pluristem’s Zami Aberman, a mechanical engineer, on adherent stromal cell therapies, and how they might become internationally commercially available. He began with discussion of how the manufacturing process changes the properties of cells and therefore how we have a requirement for equipment and processes that do not do this — the need for a scalable, 3D system from day one.
Overall the presentations had a keen focus on the PLX Technologies: the Pluristem product has completed two Phase I/II trials and is active in many regulators, from Korea to the US and UK, and covering cardiovascular, orthopedic, pulmonary and women’s health indications. The PLX cells survive for a few weeks in the site of injury, but do not engraft. By secreting growth factors they increased the survival rate in animal models in a dose-dependent manner and with a systemic effect. Of the four products, PLX-PAD, -RAD, -IMMUNE and -CNS, PLX-PAD is already in trials and has been approved by many agencies.
According to Zami, the main challenges are harvesting and scalability; however, he stated Pluristem’s PluriSphere product, patent pending, would be the next cell culturing technology owing to its 3D system and increased culture efficiency. He finished on an interesting note: cell therapy must have in-house manufacture to ensure it is known exactly how it is made. However, I wonder if this could be restrictive?
Addressing healthcare challenges posed by an aging global population, through innovative regenerative medicine technologies and advances in regulatory agencies
Our last talk was by the charismatic Gil Van Bokkelen of Athersys, Inc., and discussed how the current unprecedented demographic changes will significantly impact on healthcare costs and requirements in the future. The simple fact is, the older you get the more diseases you get and the more expensive you are to look after: and many indications do not have treatments or cures.
Providing some terrifying statistics, Gil showed us that from 2010 to 2030 there will be an 80% increase in the number of people aged 65+ years in the US, and it won’t be long before a quarter of the population will be aged 65+ in Japan. Moreover, despite public misconception that US health expenditure is mainly on prescription drugs and research, it is in fact only 10% and 6.7%, respectively; the majority is on palliative care (hospital care, nursing homes, physician services, etc.).
He next discussed the game-changing Japanese change in regulation: a clinical trial with safety and meaningful efficacy can get provisional approval and endorsement, therefore significantly earlier patient access in the development pipeline. Following from that there was information on the Phase II trials of MultiStem, which reduced stroke damage by preventing spleen-induced hyperinflammatory damage (pesky spleen!).
Gil concluded by sharing some thoughts on the need for a change in the cost of new medicinal products — we have limited resources, so although product generation is hugely expensive, making products so expensive that hardly anyone can afford to buy them is irrational. Regenerative medicine has high value, as it may actually offer a solution for many unmet clinical needs, so it can still be a profitable investment without being unaffordable.
Did you attend the meeting or have any further details? Please share your thoughts and comments below.