A New Way to Manufacture Small Batches of Biopharmaceuticals on Demand

Biopharmaceutical drugs are normally manufactured at large facilities dedicated to a single product, using processes that are difficult to reconfigure. To help make more of these drugs available, MIT researchers have developed a new way to rapidly manufacture biopharmaceuticals on demand. Their system can be easily reconfigured to produce different drugs, enabling flexible switching between products as they are needed.

“Traditional biomanufacturing relies on unique processes for each new molecule that is produced,” said J. Christopher Love, a professor of chemical engineering at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research. “We’ve demonstrated a single hardware configuration that can produce different recombinant proteins in a fully automated, hands-free manner.”

A streamlined process

One key element of the new system is that the researchers used a different type of cell in their bioreactors-a strain of yeast called Pichia pastoris. Pichia pastoris secretes only about 150 to 200 proteins of its own, compared to about 2,000 for Chinese hamster ovary (CHO) cells, which are often used for biopharmaceutical production. This makes the purification process for drugs produced by Pichia pastoris much simpler.

The researchers also greatly reduced the size of the manufacturing system, with the ultimate goal of making it portable. Their system consists of three connected modules: the bioreactor, where yeast produce the desired protein; a purification module, where the drug molecule is separated from other proteins using chromatography; and a module in which the protein drug is suspended in a buffer that preserves it until it reaches the patient.

In this study, the researchers used their new technology to produce three different drugs: human growth hormone; interferon alpha 2b, which is used to treat cancer; and granulocyte colony-stimulating factor (GCSF), which is used to boost the immune systems of patients receiving chemotherapy.

They found that for all three molecules, the drugs produced with the new process had the same biochemical and biophysical traits as the commercially manufactured versions.

With colleagues at Rensselaer Polytechnic Institute, the researchers also designed software that helps to come up with a new purification process for each drug they want to produce.

Decentralized manufacturing

The ease with which the system switches between production of different drugs could enable many different applications. With the new MIT technology, small-scale production of the drugs could be easily achieved, and the same machine could be used to produce a wide variety of such drugs.

Another potential use is producing small quantities of drugs needed for “precision medicine,” which involves giving patients with cancer or other diseases drugs that are specific to a genetic mutation or other feature of their particular disease.

These machines could also be deployed to regions of the world that do not have large-scale drug manufacturing facilities.

“Instead of centralized manufacturing, you can move to decentralized manufacturing, so you can have a couple of systems in Africa, and then it’s easier to get those drugs to those patients rather than making everything in North America, shipping it there, and trying to keep it cold,” said Crowell.

The researchers are now working on making their device more modular and portable, as well as experimenting with producing other therapies, including vaccines.

The research was funded by the Defense Advanced Research Projects Agency, SPAWAR Systems Center Pacific, and the Koch Institute Support (core) Grant from the National Cancer Institute.

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