The project, sponsored by Thermo Fisher, Ohio State and Latham Biopharm, aims at warzone use but the tech could also be applied to public quarantines, personalised medicine, and ultra-low cost vaccine manufacturing, says Govind Rao who leads the research at the University of Maryland, Baltimore County (UMBC)’s Center for Advanced Sensor Technology.
Speaking at Bioprocess International conference in Boston on Tuesday, Rao described the team’s breakthrough in large molecule manufacturing as “beyond revolutionary […]my head is still spinning.”
‘Welcome to Betty Crocker bioprocessing’
The portable tech relies on a cell-free expression platform from Thermo Fisher; it lyophilises the contents of a cell, minus the nucleus. “It’s incredible,” said Rao, “the entire [raw materials] are freeze-dried powder: welcome to the Betty Crocker world of bioprocessing. Within a few hours you are expressing a high quality protein.”
These powder kits allow rapid expression of about 500 micrograms of protein per millilitre. “Imagine no need for cold chain – you can produce on-site and administer to the patient [immediately].”
UMBC’s students even simulated conditions where soldiers use their own body heat to trigger protein production.
The team successfully experimented with human-EPO (erythropoietin), CHO (Chinese Hamster Ovary)-human EPO, and streptokinase across three bioreactors and for one batch brought expression time down to an hour and a half.
Cigarette pack reactors
Rao’s team has created 3D printed designs for their next goal: flat-chip bioreactors shrunk down to the size of cigarette packs.
The scientists are also working on making purification portable. They are aiming for a one-size-fits-all purification process to make the platform flexible, and have discovered a “self-cleaving peptide”: a split NPU (Nostoc punctiforme) intein which leaves just one column. The scheme is also looking at non-intein-based capture methods, and at polishing methods for purity.
‘It sounds nuts’
The project was prompted by a $7.9m grant from DARPA, the US Defense Advanced Research Projects Agency. Military experts believed current pharmaceutical supply methods to battlefields – sometimes requiring airdrops – were obsolete, and need to be replaced with manufacturing at the point of care – “a specific threat response without requiring specific preparedness.”
Rao told Tuesday’s conference moving biomanufacturing to the front lines echoes the decentralisation of pharma supply chains to civilians, as healthcare increasingly moves from hospitals to patient homes with the advent of technology like home diabetes tests.
“A perfect storm in healthcare is happening, with costs going through the roof.” The effects of high drug prices and bad press are “unsustainable”, he said – and as recent coverage shows, “if we don’t respond, someone else will come and fix the problem.”
“Our goal is to leverage this and replace this large [manufacturing] footprint that is the bread and butter of our industry today with a suitcase-sized device that will make GMP therapeutics at the point of care within a few hours.
“I know it sounds completely nuts.”
Field tests so have have produced G-CSF (Granulocyte-colony stimulating factor), Interferon, and antibodies using the tech.
The team still has to contend with a host of regulatory issues, and Rao recognised that this sort of expensive military medicine touches only “the 0.01 per cent.” But he said he hopes this high-end, high-tech work will fund pharmaceutical projects with a wider reach.
Cell-free production tech could be used to produce low-cost vaccines – “a tremendous paradigm shift is definitely coming” – as well as personalised medicines. Any future civil quarantines in response to flu pandemics could also provide a “jump-start” to adoption of portable tech, he said.