Bioartificial livers are devices that consist of embedded liver cells, or hepatocytes, and temporarily replace liver functions while patients wait for a transplant. Although animal studies have proven the effectiveness of the devices, clinical trials have failed to show any survival benefit yet for patients with severe liver failure.
A partnership between EMD Millipore and PharmaCell announced Tuesday aims to produce protocols and methods for the expansion, harvest and use of large-scale quantities of the liver cells, known as HepaRG cells, between the next 12 and 18 months, Robert Shaw, commercial director of EMD Millipore's Stem Cell Initiative, told In-Pharmatechnologist.com. Although large-scale methods typically use multi-layer flasks to manufacture such cells, EMD Millipore and PharmaCell are attempting to use disposable bioreactors.
“EMD Millipore is providing the technical proof of principle for scale-up from their laboratories in Massachusetts, and consulting on the work in Belgium,” Shaw said. “PharmaCell is conducting the actual development and scale-up at their facility.
“Reproducibility will be ensured by analytical comparison of the cells to standard existing tissue culture produced cells,” he continued. “The ability to ensure that a population of cells can be reproducibly produced in a manner that can be validated is critical to the success of clinical applications. The technologies developed as part of this collaboration will help enable this and move the field forward.”
Bioartificial Liver Project
The three-year, more than $10M project to develop the bioartificial livers, known as the BALANCE project, began in June 2012. It aims to bring the HepaRG cell line from in vitro optimisation, validation and technical preparation in a bioreactor, to proving the cells' safety and feasibility in a liver failure model, to eventually forging a Phase I/IIa study to prove safety and feasibility in patients with liver failure.
“For the bioartificial livers that are the result of the BALANCE project, extremely large numbers of cells are required in a reproducible and cost-effective manner,” Shaw said. “This program should demonstrate the feasibility of bioreactor-based expansion of HepaRG and show that large-scale cultures are possible.”
The EU’s Seventh Framework Programme agreed to fund more than $7.7M (€5.99M) of the total $10M (€7.79M) project. The project, which is funded through May 31, 2015, is looking to produce three main results:
- An optimised and validated bioartificial liver, a GMP manufacturing process and a GMP grade and stable human liver cell line;
- Hep-Art, one of the collaborators on the project, will further pursue clinical development of the bioartificial liver towards EMA registration and marketing together with a large industrial partner, while PharmaCell will use the GMP manufacturing process for production of the trial and commercial material; and
- BioPredic will further exploit the GMP-graded HepaRG cells.
In addition to the participating companies, academic partners at the Amsterdam Medical Centre and University of Edinburgh have joined forces to work on the project.