Health and Medicine
PUBLISHED
Gravity can help or harm manufacturing processes. When we want more gravity, for example to speed up separations, centrifuges provide an easy way to get it, but getting less gravity is much more of a challenge.
The idea of shifting operations to what was once called zero-gravity is as old as the space age, if not older. However, while the time may finally have arrived, it’s far from clear how much of the pharmaceutical industry will take place above our heads.
History of an idea
The theoretical benefits of manufacturing pharmaceuticals in microgravity are straightforward. If you’re combining liquids of very different densities, you don’t have to fight their constant tendency to separate.
More importantly, certain crystals can grow larger and with a higher degree of structure (crystallinity) in the absence of gravity, and for some medicines, that is exactly what you want.
You can’t change reactions in space. Molecules behave the same.
Professor Volker Hessel
Moreover, many molecules can take different crystal forms (polymorphs) despite having identical compositions; sometimes, the difference between these forms can be a matter of life and death. Low gravity should increase our capacity to ensure we get the forms we want.
In space, you also don’t have to worry about someone opening the lab door when the light says not to.
The idea has been demonstrated within the 25 to 65 seconds of weightlessness provided by parabolic flights, such as those conducted on the so-called “vomit comet”, but the challenges of scaling up are obvious. The International Space Station (ISS) has provided more extended opportunities, but even the medications astronauts take themselves are made on Earth.
Drugs are not the only things that would benefit from being manufactured beyond Earth’s atmosphere, but counterintuitively, they benefit from being light. All the ingredients, as well as the processing facilities, for space manufacturing need to be launched into orbit.
Launch costs have plunged in recent years, but they’re still high enough that any product needs to have an exceptional value per gram to make the process work. A machine part might be stronger if forged in microgravity, but it doesn’t have to weigh much before the round-trip price becomes prohibitive.
Professor Volker Hessel of the University of Adelaide told IFLScience that launch costs could make even common pills weighing 250 milligrams (0.01 ounces) unaffordable, even if the quality improves. However, Hessel noted the active ingredient in some drugs weighs a few micrograms.
“That’s three orders of magnitude less weight,” Hessel said. The same launch costs could get you a thousand pills instead of one, with the addition of some harmless substances on Earth to make sure you can find the pill.
When a dose of that medication costs $72,000 a month (as Myalept, a medication developed by Amryt Pharma to treat leptin deficiency, did in 2020) because manufacturers are recouping enormous Research and Development costs from a few patients, the extra costs of space production may be less of a factor.
Microgravity manufacturing today
Although many have talked about manufacturing in low Earth orbit, Varda Space Industries is the first to have a serious go at making it possible.
In 2023, they launched a satellite with an automated production laboratory attached. In February 2024, a sample of the three forms of ritonavir crystals, as well as an amorphous form of the anti-HIV drug, made in orbit, landed in the Utah Desert, six months late as a result of regulatory delays.
Varda scientists analyzed the polymorphic crystals produced and declared the test crystals to exhibit “excellent stability” in a preprint paper that has not been peer reviewed.
That’s significant, because the authors note, “ritonavir was selected for its particularly challenging polymorphic landscape”. In other words, it can be hard to keep it in the preferred form, so stability is key.
The project melted ritonavir’s Form II and cooled it, in the hope of getting Form III, which is vulnerable to turning back into other forms, so its survival is encouraging.
The claimed success inspired Varda to take a further step towards commercial production, manufacturing an undisclosed pharmaceutical on a capsule in space before having the payload land in South Australia earlier this year. Two more test capsules have since launched, one of which has returned.
How expensive is it really?
Estimates of the cost of delivering payloads to space vary, but $2,000 per kilogram ($900 per pound) is at the lower end. Projections for future drastic price reductions in launch costs are looking shakier with each Starship explosion.
It’s easy to whip out your phone and calculate that for pills weighing 50 milligrams, space production will add a trivial 10 cents per pill.
However, that ignores not only the cost of returning the pills to Earth, but more importantly, the launch cost for the equipment that will make the pills in orbit. Moreover, producing drugs usually involves a lot of solvents and other chemicals that don’t make it into the drugs themselves, all of which also need to be launched, and may weigh a lot more than the final product.
It’s also not as though our capacity is unlimited. Every satellite added to low Earth orbit takes us closer to Kessler Syndrome.
If we fill up lower orbits unsustainably, every use of space may be forced higher, with associated additional costs. How well will thousands of labs churning out widely used drugs compete for precious space with communications and weather satellites?
In that context, it’s easy to see that manufacturers will only make drugs in space when the price is high and the quality improvements significant.
Is this medicine’s future?
As expensive as clinically approved drugs are, at least while still under patent, getting their ingredients and the tools to process them into space, and the products safely back to Earth, will still add a hefty premium.
Consequently, it’s likely that for a long time to come, most pharmaceuticals will continue to be made on Earth. Space will be restricted to those that are particularly challenging to make on Earth.
Moreover, Hessel said that the question of how many drugs would even benefit from microgravity production “hasn’t been systematically tested,” even before price is factored in. Whether ritonavir is more the exception or the rule remains to be seen.
However, there is one thing even more valuable per ounce than rare-disease medications, hard as that may be to believe.
That’s a drug that is still in the experimental phase. When a potential medicine is being tested, either on animals or in clinical trials, the quantity needed is still tiny, and the benefit of maximizing quality is high. Considering how expensive it is to run a clinical trial at all, increased production costs may not matter that much.
Space could also be a good testing ground to see how potential drugs interact with tissue, allowing us to see “how a drug interacts with antigens like viruses,” Hessel said. That could inspire tweaks that make the molecular key better suit the lock.
Once made and value identified, however, we might use the product as a template for mass production down here. Nevertheless, Hessel stressed, “You can’t change reactions in space. Molecules behave the same.”
Not just price
It’s also worth remembering that the expense might not be the only drawback for space pharma. Beyond the atmosphere, radiation exposure increases.
In 2021, an experiment investigated whether pills made on Earth degraded faster on the ISS than they would at home. That’s an important question for journeys to Mars or extended stays on the Moon, as Hessel noted at the time, since radiation exposure is even greater beyond the Van Allen belts.
“Degradation by cosmic rays happens even within the ISS,” Hessel told IFLScience. “On Earth, drugs tend to decompose about 5 percent a year.” That’s why shelf lives tend to be two to three years, but it’s likely to be faster in space. Nevertheless, Hessel doesn’t think decay will present a major obstacle.
“If we keep production reasonably short and shield the machine, it should be pretty safe, at least from alpha rays. Humans and plants survive in space after all. It should only be a problem on a scale of a year or at least half a year.”
One day, the products returning from space may be so valuable that piracy becomes an issue, but Hessel doesn’t foresee people intercepting the return capsules soon.
Prospective settlers of the Moon and Mars are looking for commercial applications that might justify the vast expense, but Hessel doubts they’ll be well suited to pharmaceutical manufacturing.
Those objects’ gravity, while lower than Earth’s, make these locations less suitable for crystal-making than low Earth orbit, which, Hessel notes, is also only 400 kilometers (250 miles) away.
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