DNA analysis for early virus detection

Carnegie Mellon University’s Department of Chemical Engineering is working to create a form of biomanufacturing that will be able to scan and test for adventitious agents while biopharmaceuticals are being produced.

Biomanufacturing is defined as the production of biomaterials and molecules that can be used in applications like medicine and the processing of food and beverages. Adventitious agents are any foreign virus, bacteria, or other biological contaminant that might have found its way into a certain biopharmaceutical product.

The Department of Chemical Engineering is not undertaking this enormous project on its own, but has partnered with the biotech firms Genentech and LumaCyte. Genentech is a groundbreaking research-based biotechnology company based in San Francisco, California; LumaCyte, meanwhile, is based in Charlottesville, Virginia and primarily works on biotechnology instrumentation, or the maintenance, repair, and calibration of biomedical equipment.

LumaCyte will utilize a laser analysis and sorting instrument known as Radiance, which permits the characterization and sorting of particular cells by measuring their optical force. It is a “high-content, label-free microfluidic device.” Researchers will use both Radiance and Carnegie Mellon’s rapid DNA analysis program to quickly scan for viruses or bacteria present in bioprocess streams.

The National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) has already funded this research project, so researchers from all three parties can create and test new technologies that will improve the testing of biologic medicines while they are being produced and before they are released.

NIIMBL is an “Innovation Institute” which was formed to revolutionize the manufacturing of domestic biopharmaceuticals. It was funded by a $70 million cooperative agreement with the United States Department of Commerce’s National Institute of Standards and Technology. The organization provides funding for projects aiming to create products that save and improve lives at a more rapid pace and a lower cost. The NIIMBL-funded project aims to quickly and precisely locate viral infectivity in medicines.

This is a major innovation, because there is always a risk that viruses can infect the batch while researchers produce pharmaceuticals with biological materials like mammalian cell lines. Currently, researchers test for these adventitious agents quite late in the manufacturing process, but this project aims to create new technologies allowing biopharmaceutical batches to be tested during production. Members of the research team creating these new technologies include a professor of chemical engineering, Jim Schneider, and Adjunct Professor Todd Pryzbycien.

“If you don’t find out about infection until very late in the process, you will have wasted a lot of time and money as more downstream equipment and product becomes infected. Current infection detection techniques, such as cell-based assays and polymerase chain reaction, can take days to complete,” reported Schneider in a press release. “Our methods can provide readout in less than 15 minutes, which enables a routine, continuous type of testing that could detect infections almost as soon as they take hold.”

Schneider and Pryzybycien have been working on rapid DNA analysis for many years. Schneider’s lab has already developed a rapid DNA analysis technique which looks in the process streams used to create pharmaceuticals, and localizes bacteria and viruses in these streams. To accomplish this, researchers perform rapid electrophoresis to separate tagged and untagged DNA so researchers can discern whether virus or bacteria are present in a given process stream.

“The focus of NIIMBL is to translate existing technologies into biomanufacturing contexts. One of the top priorities that the industry has identified is rapid adventitious agent screening. As one of the first four projects funded by NIIMBL, this research with LumaCyte and Genentech shows our commitment to collaboration between academia and the pharmaceutical industry,” Schneider said in a CIT press release.