A new way to manufacture small batches of biopharmaceuticals on demand mit news

“Traditional biomanufacturing relies on unique processes for each new molecule that is produced,” says 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.”

Biopharmaceuticals, which usually have to be injected, are often used to treat cancer, as well as other diseases including cardiovascular disease and autoimmune disorders. Most of these drugs are produced in “bioreactors” where bacteria, yeast, or mammalian cells churn out large quantities of a single drug. These drugs must be purified before use, so the entire production process can include dozens of steps, many of which require human intervention.

As a result, it can take weeks to months to produce a single batch of a drug.

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. Yeast can begin producing proteins much faster than mammalian cells, and they can grow to higher population densities. Additionally, 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.

Reconfiguring the system to produce a different drug requires simply giving the yeast the genetic sequence for the new protein and replacing certain modules for purification. 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. Using this approach, they can come up with a new procedure and begin manufacturing a new drug within about three months. In contrast, developing a new industrial manufacturing process can take 18 to 24 months.

The ease with which the system switches between production of different drugs could enable many different applications. For one, it could be useful for producing drugs to treat rare diseases. Currently, such diseases have few treatments available, because it’s not worthwhile for drug companies to devote an entire factory to producing a drug that is not widely needed. With the new MIT technology, small-scale production of such drugs could be easily achieved, and the same machine could be used to produce a wide variety of such drugs.

“You could be prototyping many different molecules because you can really build processes that are simple and fast to deploy. We could be looking in the clinic at a lot of different assets and making decisions about which ones perform the best clinically at an early stage, since we could potentially achieve the quality and quantity necessary for those studies,” Routenberg Love says.