New system that can produce different drugs offers hope for orphan diseases.
MIT researchers have developed a small, transportable pharmaceutical manufacturing system that can be reconfigured to produce different drugs on demand.
“The goal of this project was to build a small-scale, portable unit that was completely integrated, so you could imagine being able to ship it anywhere,” said senior study co-author Klavs Jensen. “And as long as you had the right chemicals, you could make pharmaceuticals.”
This system even has the potential to be used to rapidly produce drugs needed during an unexpected disease outbreak or act as a prevention tool for drug shortages if a manufacturing plant is shut down.
“Think of this as the emergency backup for pharmaceutical manufacturing,” said senior study co-author Allan Myerson. “The purpose is not to replace traditional manufacturing; it's to provide an alternative for these special situations.”
Typically, drug manufacturing can take weeks or months leaving little to no flexibility to respond to drug demand surges, and can lead to repercussions if one of the plants is shut down.
A study published in Science created a compact and portable device that can produce Benadryl, lidocaine, Valium, and Prozac formulated as solutions or suspension. This new system allows researchers to manufacture approximately 1000 doses of a drug in 24 hours.
“In many cases we were developing syntheses of targets that had never been done in a continuous flow platform,” said senior study co-author Timothy Jamison. “That presents a lot of challenges even if there is a good precedent from the batch perspective. We also recognized it as an opportunity where, because of some of the phenomena that one can leverage in (a flow-based system), you can make molecules differently.”
In the first of the 2 modules, the chemical reactions that are necessary for synthesizing each drug take place. These reactions take place at temperatures of up to 250 degrees Celsius and pressures up to 17 atmospheres.
Researchers are able to easily reconfigure the system to produce different drugs by trading in different module components.
“Within a few hours, we could change from one compound to the other,” Jensen said.
Next, in the second module, the crude drug solution is purified by crystallization, filtered, and then dried to remove the solvent. Its then either dissolved or suspended in water as the final dosage forms.
In order to ensure that the formulated drug solution is the right concentration, an ultrasound monitoring system was incorporated.
The small scale system has the potential to be used to make smaller amounts of drugs that are normally much more expensive when produced in a large scale plant. Orphan drugs that are needed by only a small portion of patients could benefit from this new system.
“Sometimes it's very difficult to get those drugs, because economically it makes no sense to have a huge production operation for those,” Jensen said.
Additionally, regions that have little pharmaceutical storage facilities could find the system useful as well, since the drugs can be produced on demand and in return eliminate the need for long term storage.
Now, researchers are in the second phase of their work and are making the system 40% smaller. They are also looking to make the system produce drugs with more complex chemical syntheses. Furthermore, researchers are in the process of producing tablets that are more complicated to manufacture than liquid drugs.
“The idea here is you make what you need, and you make a simple dosage form, because they're going to be taken on demand,” Myerson said. “The dosages don't have to have long-term stability. People line up, you make it, and they take it.”