Hosted by Open Bioeconomy Lab and Cambridge SynBio IRC and funded by the Redistributed Manufacturing in Healthcare Network (RiHN), a recent workshop explored the “Challenges and opportunities for Cell-Free Biomanufacturing in Crisis Zone”.
The aim of the workshop was to identify key challenges for the development and implementation of cell-free technologies and better understand whether or not they offer a realistic solution to healthcare problems in crisis zones.
Experts from science, humanitarian work, medicine, regulation and other fields of interest convened and kicked off with breakout groups to summarise “Three things you should know” about the topic.
In terms of the principles of cell-free biology, important information includes that lysate-based cell-free or transcription-translation (often called TX/TL) systems are being produced from an increasing number of organisms providing greater diversity of metabolic abilities and particularly post-translational modifications as well as increasing the number of “test beds” for protoyping in vivo organism engineering. Technology transfer was highlighted as a major consideration for distributed biomanufacturing as there are considerable skill and infrastructure considerations in what is still a niche field. In this regard, “shelf life” and stability of extracts was highlighted as one of the most important logistical considerations. The challenge across all cell-free work was characterised as variability: between researchers, between batches, between protein expression experiments.
Having discussed the challenges, the translation of cell-free technologies group emphasised the opportunities in terms of allowing for freeze-dried, distributable manufacturing of diagnostics and therapeutics. Their takeaway was that we are closer than people think for applying cell-free systems to diagnostics and protein vaccines, for example these can already produce vaccines at $0.40 a dose which are stable for 4 days at 40C. However, protein therapeutics are harder than vaccines because a lot of protein is needed wihtout depending on the immune system to act as the transducer in the system. The group concluded that the main gap is scale and the need to shape the systems in which medical biomanufacturing operates as no one has made a medicine this way before. Costs are still an issue for some applications but for others they are economical e.g. small molecule sensing is relatively inexpensive at $0.10 for lead testing.
The group who are expert in distributed manufacture of healthcare technologies thought we should know that the most important thing is assessing how and when distributed manufacture provides better clinical outcomes and why e.g. is the product better, feaster, cheaper or all of the above? They also pressed for being careful not to get too polarised in terms of thinking: distributed does not necessarily mean last mile and parts of the procoess could be more centralised in hubs. As well as manufacturing being appropriate to the context, its outcomes need to be predictable, repeatable and robust across the network of manufacturers, which could clash with the challenges raised around high levels of variability in cell-free engineering at present.
Focusing in specifically on the topic of healthcare technologies in crisis zones, this breakout group emphasised resource inventory and management as having limitations which are unique to crisis or conflict zones. Technology failures and unreliability are almost inherent in the context which results in the reallocation and innovative application of technologies beyond the purpose for which they were originally designed. The topic of self-dependency came up as one to consider in terms of the politics and economics of distributed manufacturing in crisis or conflict zones.
We then went on to discuss in three breakout groups:
- the future of cell-free technology
- deployment of health technologies in crisis zones including supply chains, infrastructure, human resources
- medical device regulations, procurement policies, health systems policies and other relevant factors.
A report is being drafted to summarise in more detail the considerations and a webinar and Q&A will be organised in upon publication.