The biotech industry is beginning to replace metal vats in the manufacturing process with single-use plastic bags. But concerns remain about whether compounds could leach out of the films inside the bags. Such compounds could negatively affect cells during biomanufacturing or persist through purification processes and end up in protein drug formulations, causing a potential risk to patients.
A team led by Jonathan Bones of the National Institute for Bioprocessing Research & Training, in Ireland, has measured the compounds released by 34 single-use bags from five suppliers (Anal. Chem. 2018, DOI: 10.1021/acs.analchem.8b01208).
The team looked for two kinds of molecules: extractables, which represent all possible compounds that could be released, and leachables, which would be present only under normal conditions. To identify the extractables, the researchers extracted bag films with four solvents chosen to represent potential worst-case scenarios in biomanufacturing. They obtained the leachables by using cell culture medium as an extraction solvent. The team used mass spectrometry to analyze semivolatile and nonvolatile compounds, trace elements, and organic solvent residues.
One statistical analysis method clustered the bags’ data into groups based on the date of manufacture, most likely due to different types of polyethylene used to make the bags. The oldest bags were manufactured in 2006; the newest, in 2016. Another data-clustering method divided the bags into five distinct groups, classified by the type of polymer in the inner layer followed by the extraction solvent.
In the case of nonvolatile compounds, the researchers identified 113 extractables and 14 leachables, six of which were not among the extractables. The researchers say that the presence of leachable compounds that weren’t also extractable provides evidence that just analyzing what can be extracted from bags may not be sufficient to model actual culture conditions.