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

Abstract

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. 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.

Keywords: Additive manufacturing of drug products; Advanced drug delivery systems and technologies; Clinical pharmacokinetics and pharmacodynamics; Extra-terrestrial design of formulations; Future fabrication of pharmaceuticals; Pharmacy in space; Stability of medicines.

Graphical abstract

Fig. 1

(A) Comparison of risk of radiation induced death (% REID) from circulatory diseases and cancer for different space missions in 45-year-old female and male never-smokers. Reproduced with permission from (Cucinotta et al., 2013) (B) Comparison of average telomere length of three crewmembers (A, B, and C) before, during and after spaceflight. Reproduced with permission from (Luxton et al., 2020).

Fig. 2

(A) Self report scores on reactions to confinement by crewmembers (identified by lower case letters a-f) on the Mars500 simulated mission. Measures of psychological distress include the Profile on Mood State (POMS), which is a short form comprising a list of 37 adjectives for which crewmembers indicated the degree each described themselves. Reproduced with permission from (Basner et al., 2014). (B) Average duration of sleep before, during, and after shuttle mission. Reproduced with permission from (Barger et al., 2014)

Fig. 3

Images of astronaut exercising on (A) Interim Resistive Exercise Device (iRED) (donning squat harness pads), and (B) Advanced Resistive Exercise Device (ARED). Reproduced with permission from (Patel et al., 2020).

Fig. 4

(A) Effects of the spaceflight environment on pharmacokinetics of drugs. Reproduced with permission from (Kast et al., 2017). (B) Table showing the differing concentrations of cytochrome P450 enzymes in mice exposed to 30 days of space flight (SF), the ground control (GC), and the recovery group (RA). Reproduced with permission from (Moskaleva et al., 2015).

Fig. 5

Table showing the difference in muscle unloading characteristics between human and rodent models. Reproduced with permission from (Qaisar et al., 2020).

Fig. 6

(A) Figure showing the working principle of the ZGMMD. The sample moves at a pre-defined acceleration (x) and force sensors measures the force applied by the sample (f), (B) Schematic of ZGMMD Phase II, (C) 3D views of ZGMMD Phase II design. Reproduced with permission from (Morrow et al., 2015).

Fig. 7

Overall schematic of alternative synthesis and manufacturing strategies for the on-site production of medicines in space. Created with BioRender.com.

Fig. 8

(A) Schematic representation of the Chemputer highlighting the four modules used (reactor, filter, separator, and rotary evaporator). (B) Photograph of one Chemputer setup with the modules highlighted in correspondence to the schematic. (C) Chemical reaction and (D) schematic of sildenafil synthesis. Reproduced with permission from (Steiner et al., 2019).

Fig. 9

(A) Schematic representation of the reconfigurable system for continuous drug synthesis. At the top, the row represents the different modules; coloured modules are active, while grey boxes represent inactive modules. (B) Table showing the breakdown of process time for each API tested, Reproduced with permission from (Adamo et al., 2016).

Fig. 10

Biologically derived medicines on demand, Bio-MOD, a miniaturized platform for biologics manufacturing. (A) Photograph of the suitcase-sized platform showing the components. (B) Process workflow of therapeutic protein manufacturing. (C) Table showing yield, purity, and activity of G-CSF-His produced in the Bio-MOD over 3 runs. Reproduced with permission from (Adiga et al., 2018).

Fig. 11

(A-C) Photographs of volumetric printer used to produce printlets loaded with paracetamol (legends 1-9 included on the left). (D-E) Schematic of the volumetric printer system. (F) Sequential images of the printing process. Reproduced with permission from (Rodríguez-Pombo et al., 2022).

Fig. 12

(A) Photo of the setup of the LBM 3D printer mounted in an Airbus A310 ZERO-G. (B) Top view of wrenches manufactured in microgravity. The base plate has a size of 106.5 × 85.5 mm². Reproduced with permission from (Zocca et al., 2019).

Fig. 13

Diagram describing the design criteria for equipment in space. Reproduced with permission from (Snyder et al., 2019).

Fig. 14

Schematic illustrating a proposed regulatory framework. Created with BioRender.com.