To infinity and beyond: Strategies for fabricating medicines in outer space

Recent advancements in next generation spacecrafts have reignited public excitement over life beyond Earth. However, to safeguard the health and safety of humans in the hostile environment of space, innovation in pharmaceutical manufacturing and drug delivery deserves urgent attention. In this review/commentary, the current state of medicines provision in space is explored, accompanied by a forward look on the future of pharmaceutical manufacturing in outer space. The hazards associated with spaceflight, and their corresponding medical problems, are first briefly discussed. Subsequently, the infeasibility of present-day medicines provision systems for supporting deep space exploration is examined. The existing knowledge gaps on the altered clinical effects of medicines in space are evaluated, and suggestions are provided on how clinical trials in space might be conducted.

Highlights

• Space is a hostile environment that threatens human health and drug stability.

• Data on the behaviour of medicines in space is critical but lacking.

• Novel drug manufacturing and delivery strategies are needed to safeguard crewmembers’ safety.

• Chemputing, synthetic biology, and 3D printing are examples of such emerging technologies.

• A regulatory framework for space medicines must be implemented to assure quality.

An envisioned model of on-site production and delivery of medicines in space is proposed, referencing emerging technologies (e.g. Chemputing, synthetic biology, and 3D printing) being developed on Earth that may be adapted for extra-terrestrial use. This review concludes with a critical analysis on the regulatory considerations necessary to facilitate the adoption of these technologies and proposes a framework by which these may be enforced. In doing so, this commentary aims to instigate discussions on the pharmaceutical needs of deep space exploration, and strategies on how these may be met.

Introduction

Over 50 years ago, the Apollo 11 Moon Landing inspired millions to imagine life beyond Earth. However, in contrast to the rapid pace at which the Apollo Project saw success, space exploration has remained largely stagnant for the past five decades. This is despite the entry of new government space agencies, such as the European Space Agency (ESA) and the Japan Aerospace Exploration Agency (JAXA), on top of the two key players of the 20^th-century Space Race, namely the (US) National Aeronautics and Space Administration (NASA) and the Roscosmos (then the Soviet space program). Activities by major government space agencies have largely focused on unmanned explorations such as NASA’s Mars Exploration Program, or crewed space flights to the International Space Station (ISS). Nonetheless, recent developments in next generation spacecrafts and reusable launch systems by private aerospace companies, such as SpaceX, have spurred a new era of deep space exploration, with the ambition of launching crewed space flights to Mars in the next 5–10 years (Do et al., 2016; SpaceX, 2021).

Private space companies are leading the development of the next generation of spacecrafts, with applications ranging from deep space exploration (e.g. SpaceX) to affordable satellite deployments (e.g. Rocketlab). Significant strides have been made towards the goal of landing the first human on Mars, reigniting public excitement towards space exploration. In 2020, SpaceX launched the first NASA crew rotation flight to the ISS on an American commercial spacecraft (the SpaceX Crew Dragon spacecraft), ending almost a decade of American dependence on the Russian Soyuz spacecraft for such missions (NASA, 2020b). The success of the Crew Dragon also marked the first, and to-date only, reusable crewed or cargo spacecraft. It also set precedence in 2021 for private space tourism through the Inspiration4 mission, which saw four private citizens on board a successful orbital spaceflight. For deep space exploration, SpaceX is developing and testing a fully reusable transportation system known as Starship for both crew and cargo, with the aim of Mars colonization (Denis et al., 2020).

While significant progress in aerospace engineering is being made to realize deep space exploration and space tourism, more attention needs to be paid towards the unique medical problems faced during space travel. Astronauts experience prolonged exposure to space radiation, microgravity, isolation, and confinement (Afshinnekoo et al., 2020). These hazards and stresses cause unwanted systemic and physiological effects, such as increased cancer risk, muscle degeneration and bone loss, cardiovascular and circadian rhythm dysregulations, and central nervous system impairments. Critically, in a medical emergency, an urgent return to Earth is impossible (Grigoriev et al., 1998; Houtchens, 1993). Despite the strict medical and psychological standards that astronaut candidates must meet prior to selection, several ailments are still consistently encountered, highlighting the need for medication on board. However, these physiological changes could in return lead to alterations in pharmacokinetic and/or pharmacodynamic profiles of drugs administered in space. As such, alterations to drug doses and release profiles might be necessary to achieve desirable clinical efficacy. Yet, despite more than five decades of manned spaceflights, few data are available on drug pharmacokinetics in space (Kast et al., 2017).

The extended period away from Earth during deep space exploration missions also warrants a thorough evaluation of the long-term storage of medicines, and specially, their on-site production. Medical supplies in Space are currently maintained through regular resupply missions to the ISS, but this system cannot support missions to Mars (and beyond) given the significantly longer distance. Medicines also typically have shelf lives that range between 1 and 5 years (Lyon et al., 2006), which would be inadequate for long-term missions especially if a temporary residence on Mars is planned. Another concern is how prolonged exposure to space radiation could affect drug stability, alter components, or even create toxic by-products. Simple strategies such as using adequate packaging, storing excipients and drugs separately and in their solid or powdered form, or storing them at cryogenic temperatures, could help maintain drug stability. On-site production of medicines could also address these concerns, but to do so, the infrastructure and systems by which medicines are manufactured must be adapted to work in zero and varying magnitudes of gravity.

As humanity looks to Mars and beyond, technologies that are out-of-this-world are being explored as potential solutions to the challenges of deep space exploration. Herein, an overview of the hazards and medical problems associated with spaceflight that warrant medical intervention. We subsequently address how the pharmacokinetic and pharmacodynamic changes that can occur in space due to the previously described physiological changes. Present-day strategies for the manufacture, storage, and management of medicines in space are introduced to set the scene, before providing a forward look on emerging technologies that could be adopted to support on-demand manufacturing of medicines and medical devices. These technologies are namely Chemputing, synthetic biology, and 3D printing. Finally, we leave readers with our perspectives on the prospects of medicine manufacturing in space, including a discussion on the regulatory hurdles that need to be tackled for successful implementation.

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Iria Seoane-Viaño, Jun Jie Ong, Abdul W. Basit, Alvaro Goyanes, To infinity and beyond: Strategies for fabricating medicines in outer space,
International Journal of Pharmaceutics: X, Volume 4, 2022, 100121, ISSN 2590-1567, https://doi.org/10.1016/j.ijpx.2022.100121.