Microgravity drug research expands from ISS crystal studies to commercial manufacturing

NASA has enabled scientists to study the impact of microgravity on drug development for decades, beginning with the Space Shuttle. A private space company, Varda Space Industries, has begun flying small, uncrewed capsules equipped with autonomous bioreactors that spend a few weeks to months in microgravity that can process pharmaceuticals in the absence of gravity, and Varda announced a collaboration with United Therapeutics Corporation to explore the use of microgravity to develop improved treatments for rare lung disease.

There have been some notable successes during this timeframe, such as the ability to grow a more uniform crystalline form of the cancer drug Keytruda in 2019. This opened up the possibility of administering the drug via injection rather than requiring a patient to spend hours in a clinic setting to receive the drug intravenously.

On Tuesday, May 12, Gerard Capellades, an assistant professor of chemical engineering in the Henry M. Rowan College of Engineering, plans to send crystallization experiments into Earth’s orbit aboard the International Space Station. Through this research, he hopes to better understand how microgravity affects the formation of crystals like those in tablets and powder-filled capsules, with an eye toward improving production of these drugs.

Capellades’ experiments will be conducted inside Redwire’s automated platform for growing high-quality protein crystals in microgravity called PIL-BOX. While others have crystallized drugs in space before, previous experiments have focused on crystals made of one substance; Capellades’ experiment will be the first to incorporate an additive to this process.

Pharmaceutical tablets, semiconductors, steel, chocolate, even kidney stones are all crystals. Molecules in solution first travel to the crystal surface, and then attach themselves to the growing crystal. Microgravity slows down this early movement and, often, the overall rate of crystal growth. This results in more defined, higher quality crystals.

Capellades expects to see crystals grown on the ISS during this experiment to develop more slowly, resulting in a more homogenous product. Previous experiments found that crystals of blood-sugar regulating insulin were unusually large and well-ordered when grown in space. Crystal size and orderliness can affect the release of a drug, potentially creating opportunities to improve delivery.

Currently, crystalline drugs contain mostly single substances. Capellades is interested in adding a second safe ingredient to generate pharmaceutical alloys. For his experiments, Capellades will crystallize common substances like acetaminophen with purple dyes serving as additives, using color as a visual marker for their distribution inside the crystal. The experiments will travel to the ISS onboard the SpaceX CRS-34 commercial resupply mission.

For this latest investigation, Rowan University is working on behalf of Redwire to advance mutual research opportunities. Redwire is funding the study through a contract from the NASA In-Space Production Applications program. Once the prepared PIL-BOX is in place on the ISS, the on-orbit operations team will initiate an automated program to start the crystallization process, and a microscope camera mounted inside the module will take pictures every few minutes so the team on Earth can watch the experiment unfolding in near-real time.

NASA subsidized much of this work, typically paying the considerable costs to transport research to the ISS and for astronaut time to conduct research there. There were, however, trade-offs, such as long lead times to get research into space. Nevertheless, it has become clear that there could be some commercial applications for making drugs in space.

Varda launched the first of its vehicles, W-1, in mid-2023, and five other vehicles have launched since then. As part of the agreement with United Therapeutics, Varda and United Therapeutics will use microgravity’s influence on the structure and crystallization properties of therapeutic compounds in order to improve their stability and delivery.

Regardless of the results, drug companies may not shift manufacturing into orbit just yet, but advances in space technology could make off-Earth production increasingly feasible in the future. Capellades foresees drug companies using space-grown crystals as seeds for better crystal growth on Earth, in cases where the additive stabilizes a new crystal structure. Full, in-space production of crystalline alloys is more likely to make sense for high-value materials used only in tiny quantities, for instance, for certain semiconductors or laser optics.