Manufacturing of pharmaceutical drugs in a low orbit.
Updated: 2024-02-24
Created: 2018-11-01
Status
Many experiments have been performed and larger crystal have been grown in microgravity to improve drugs made on Earth, but manufacturing drugs themselves with the intent to sell has not been performed.
Why & Solution
Microgravity changes how crystal structures develop and in the process creates better samples than can be grown on Earth. Improving the 3D structure can have a positive impact on drug delivery, manufacturing and storage. A high percentage of pharmaceutical company executives (60%) said the space economy will have a high disruption on their sector in the coming decades. In a nutshell, space affords Big Pharma unique conditions in order to improve their drugs and potentially find new treatments. A long-term goal is the manufacturing of pharmaceuticals in a low orbit. While manufacturing in a low orbit could improve drugs, it could also increase the price.1
Liquid-liquid separation and chemical extraction are key processes in drug manufacturing and many other industries, including oil and gas, fragrances, food, wastewater filtration, and biotechnology. MIT spinout Zaiput Flow Technologies launched a novel continuous-flow liquid-liquid separator that makes those processes faster, easier, and more efficient. Today, nine pharmaceutical giants and a growing number of academic labs and small companies use the separator. Having proved its efficacy on Earth, the separator is now being tested as a tool for manufacturing drugs and synthesizing chemicals in outer space.2
In space, microgravity lets materials grow without encountering walls, and it allows them to mix evenly and hold together without traditional supports. And a nearby ultrahigh vacuum helps things form without impurities. In microgravity, crystals can grow larger; in one experiment, crystals made from proteins grew to be 6 cubic millimeters, on average, compared with 0.5 cubic millimeters here on Earth. Once grown, those crystals can be analyzed to determine the proteins' 3D structures, which can help inform new strategies for drug discovery. Growing other crystals, like those used to manufacture drugs or those that can detect gamma-rays and neutrons, in space so that they're bigger and purer can make the resulting material higher-quality.3
For drug delivery, uniformity is ideal, but it will still be some time before Merck is manufacturing drugs in space.5
Paul Reichert, a research scientist at Merck pharmaceuticals, has been an advocate for zero gravity drug development for 25 years.
Weightless drug manufacturing, he says, would enable engineers to better control chemical processes, especially when it comes to synthesizing complicated large-molecule medicines. Reichert has never left Earth, but he has designed more than a dozen experiments performed by astronauts aboard the space shuttle and the International Space Station. Still, progress is slow. “I’ve done 14 experiments in space in 24 years,” he says. “I can do 14 experiments in a day here on Earth.” Kelly hopes that more pharmaceutical experiments will be done on the Space Station, but he says an even better research site is the Moon: “It’s perfectly designed, and placed at a good distance. It’s got a sixth of the gravity of Earth, and has no atmosphere.”6
An Astropharmacy proposal was awarded for NASA Innovative Advanced Concepts (NIAC) Phase I.
Disease is an inherent part of being alive, and thus disease prevention, diagnosis and treatment will be critical to human deep space missions. Pharmaceuticals are used to diagnose, treat, cure or prevent disease, but suffer from lack of stability on Earth and even more so in the space environment. What if small quantities of pharmaceuticals could be made in space, on site, on demand? An important class of therapeutics, the biopharmaceutical or ‘biologic’ (peptide or protein drugs) would be particularly amenable to in space manufacturing. Many of the medical conditions and emergencies that astronauts are known to - or could likely – face could be treated effectively with these agents. These protein-based drugs, approved by the FDA, are now used in the clinic to treat embolisms, hemorrhages, renal stone formation, bone loss, infection, thrombotic complications, etc. Unfortunately, biologics degrade in 6 months, even with refrigeration. We propose a concept to tailor-make drugs, initially non-glycosylated biologics, by pre-programming cells that are space hardy due to being in the spore form, to produce them with the addition of ~1 mL of sterile medium using a lightweight, small volume system adapted from standard laboratory protocols and enabled by judicious genetic engineering prior to launch. Ultimately, a more flexible system could be considered that eliminates the need for pre-programming cells where a dried cell-free transcription/translation (TxTl) system is used instead for production, but a similar purification protocol. This strategy could be extended to glycosylated biologics as well. It’s a concept we term an “Astropharmacy.” This on-demand approach removes concerns about pharmaceutical degradation due to time or radiation during space travel, and minimizes the resources needed to provide safe effective pharmaceuticals needed to keep crew members healthy.
The proposed work has four objectives:
- We will raise the TRL to 3 by (1) the synthesis and purification of biologics, (2) testing their purity and activity, and (3) quantifying parameters for production. We have chosen two drugs—G-CSF and Teriparatide
- Assess requirements for implementation in space (mass, etc.) in the context of a long-stay Mars mission
- Identify key knowledge gaps & outline roadmap for technology development
- Assess the impact of technology for terrestrial applications
If successful in developing the Astropharmacy technology, the quality of astronaut healthcare will be improved by eliminating concerns of biologic drug degradation. Finally, such systems could have spin-offs for on-demand, on-site production of small quantities of other useful peptides/proteins in space, as well as on Earth, an economical path forward for orphan drugs, and improved stability for prototyping genetic circuits in cell-free systems.
Angiex utilized the ISS National Laboratory to test a novel cancer therapy that targets both tumor cells and the endothelial cells of tumor blood vessels. Angiex was awarded a MassChallenge “Technology in Space Prize” from the ISS National Laboratory and Boeing in 2016.
Earthly Solution Risk
High as research for better drugs is very active.