Expiration analysis of the International Space Station formulary for exploration mission planning

Space is an extreme environment with unique stressors and limited access to Earth-standard medical care. As NASA and partners plan for long-duration deep space missions, astronauts face increased risk of adverse medical conditions relative to low Earth orbit. Pharmacological agents are key countermeasures; astronauts on the ISS report frequent self-administration of medications for pain, congestion, circadian disruptions, and allergies. However, for exploration missions (e.g., up to ~36 months to and from Mars), medication expiration, lack of resupply, and no emergency evacuation create operational challenges. Ensuring a safe and effective on-board pharmacy requires understanding medication stability and potency. Stability testing standards (ICH/FDA) define storage conditions and labeled shelf-lives, with acceptable potency typically 95–105%. Labeled expiry indicates a minimum guaranteed period under recommended storage and sealed packaging, not necessarily the true shelf-life. Given limited public access to U.S. shelf-life data, establishing a comprehensive repository of labeled shelf-lives for the ISS formulary is operationally important.

Background literature highlights frequent medication use on ISS and identifies common self-treated conditions. Stability guidance from ICH, adopted by FDA and other regulators, governs testing across environmental conditions and container-closure systems, with potency specifications (95–105%) to mitigate risks of inefficacy or toxic degradation. Prior spaceflight studies suggest potential for accelerated degradation of certain medications stored aboard the ISS relative to terrestrial controls, though repackaging differences complicate attribution. Earlier work (e.g., Blue et al., 2019) discussed challenges in supplying a pharmacy for exploration missions and provided preliminary shelf-life data for a subset of ISS medications, but did not cover the entire formulary or multiple international sources. The present study expands on this by cataloging shelf-lives for the full 2023 formulary using multiple international registries.

The authors obtained a comprehensive NASA ISS medical manual via FOIA (received August 2, 2023) listing medications, strengths, routes, quantities, comments, and locations for the 2023 ISS formulary. Medications were organized by kit and screened for inclusion. They cross-referenced each medication with U.S. NDAs/monographs and the 2023 AHFS Drug Information compendium to identify any U.S. shelf-life data. Because U.S. expiry data are often proprietary and not publicly labeled, the authors then used four international online repositories to obtain labeled shelf-life data: Electronic Medicines Compendium (emc) and Medthority (UK/EU, aligned with EMA and MHRA), MedSafe (New Zealand), and ARTG (Australia). The USP Dictionary guided international nomenclature matching. Additional public sources were considered if they met credibility criteria (expertise, trustworthiness, reproducibility, quality) via a Stanford Credibility Tool (scored 0–4). Inclusion criteria: OTC and prescription products; brand and generic; same API, route, dosage form, and strength as the ISS formulary. If an exact strength was unavailable, the closest strength was recorded (marked with an asterisk). Exclusion criteria: differing route; combination products not matching ISS APIs; products no longer marketed/distributed in the U.S.; case-by-case exclusions based on indication, formulation, or purpose relative to the ISS formulary. Diluents (sterile water for injection/reconstitution) and exact duplicates across packs were excluded from final analysis. Data handling: Shelf-life data points (in months) were compiled in Microsoft Excel and presented by country/source. For each medication with any data, both the minimum and maximum labeled shelf-life across all sources were determined. These min/max values were used to construct Kaplan–Meier survival curves (Excel add-in) to visualize survival of medications remaining in-date over time (0–60 months), using both minimum and maximum labeled shelf-lives. Analyses reflect terrestrial labeled shelf-lives for products in original manufacturer packaging and storage conditions. Data reflect the public domain as of August 2023.

- ISS inventory: 111 total medications across five color-coded kits. After excluding 2 diluents and 3 duplicates, 106 unique drug products remained for analysis. - Data availability: No expiration data for 15/106 (14%). Shelf-life data obtained for 91/106 (86%). - Shelf-life distribution (original packaging, terrestrial): Using each medication’s maximum labeled shelf-life across sources, 54/91 (59.3%) had shelf-life ≤36 months. Using each medication’s minimum labeled shelf-life, 89/91 (97.8%) had shelf-life ≤36 months. - Early expirations: Fourteen medications will expire by 24 months (by maximum labeled shelf-life), spanning categories including ophthalmic lubricant, ALS medication, anaphylaxis treatment, benzodiazepine, antianginal, corticosteroids (two), local anesthetic, topical urinary jelly, antibiotics (two), antipsychotic, inhaler, and ear-wax removal agent. The earliest medication expiration occurs at 18 months (an ophthalmic lubricant), implying low risk for lunar missions (~18 months) but notable risk for Mars missions (~36 months). - Packaging/repackaging: Reported shelf-lives are for original packaging; ISS repackaging may shorten stability. Supply chain timelines (up to ~300 days) can further reduce functional shelf-life by the time NASA receives and packages medications. - Variability across regions/manufacturers: Shelf-lives varied between brand/generic and across UK/EU, NZ, and AU sources. Example: promethazine tablets up to 60 months (NZ/AU) versus 36 months (UK/EU). Some products lacked comparable forms/strengths across regions, leading to use of nearest strength (marked with asterisk in tables). - Diluents and form-specific notes: Sterile water shelf-life ranges 18–60 months depending on container type/size; excluded here as ISS comments indicate use as included diluents with specific drugs. Some ISS products (e.g., benzocaine swabstick) had data only for different formulations (e.g., gel), which were excluded from final analysis. - Kaplan–Meier visualization (n=91): Shows cumulative survival of medications in-date over 5 years; solid line (maximum) and dashed (minimum) illustrate that more than half would be expired by 36 months under maximum labeled shelf-life assumptions.

The findings highlight a substantial risk that many ISS formulary medications will expire during a Mars-class mission without resupply or extension strategies. Even with maximum labeled shelf-lives, over half of medications would exceed expiry by 36 months, and several expire by 24 months, raising the likelihood of therapeutic failure when treating in-flight conditions. Proprietary constraints in the U.S. hinder access to labeled shelf-life data, prompting reliance on international registries with similar stability standards. Differences in excipients, packaging, and retest standards can cause regional variability; collaboration or importation might offer access to products with longer labeled shelf-lives. Operational factors further reduce effective shelf-life: supply chain durations can consume months before launch, and ISS repackaging may shorten stability. Prior research suggests faster degradation in space, potentially driven more by repackaging and storage conditions than radiation alone, meaning terrestrial labeled data likely overestimates in-flight stability. Comparisons with prior work (e.g., Blue et al.) show general agreement but underscore the present study’s broader scope and inclusion of multiple international sources. These results provide concrete inputs for mission pharmacy planning, risk assessment, selection of formulations/packaging with longer shelf-lives, and consideration of shelf-life extension pathways.

This study compiles terrestrial labeled shelf-life data for the complete 2023 ISS formulary using multiple international registries, filling a critical public knowledge gap. More than half of medications are projected to expire before 36 months, the approximate duration of a Mars mission, and some by 24 months. Mission planners should consider strategies to mitigate therapeutic failure risk, including: selecting products with longer labeled shelf-lives and favorable packaging; leveraging expiration date extension programs; optimizing logistics to minimize preflight time; and exploring alternative solutions such as on-demand manufacturing and formulation innovations. Future research should include space-relevant stability studies, PK/PD evaluations in microgravity, improved medication-use tracking, and integration of pharmacogenomics to personalize therapy. Ultimately, exploration missions will require extending medication viability to full mission durations or accepting increased risk associated with using expired products.

- Terrestrial focus: Shelf-lives reflect labeled expiries in original manufacturer packaging under recommended terrestrial storage, not in-flight conditions. Space-specific factors (repackaging, microgravity, radiation, temperature/humidity fluctuations) may accelerate degradation. - Data completeness: Publicly available data through August 2023 only; 14% of formulary had no accessible expiry data. U.S. labeled data are often unavailable due to proprietary practices. - Form/strength substitutions: Some data points use nearest available strengths or different dosage forms/containers (noted with asterisks), which may not exactly match ISS products. - Packaging/container variability: Stability varies across container-closure systems (e.g., vials, syringes, ampoules, blister packs, HDPE bottles); ISS repackaging may differ from sources used. - Injectable products: Some surrogate forms (e.g., ampoules) were used where exact ISS-equivalent packaging data were unavailable; safety/feasibility of certain containers (e.g., ampoules) in space is limited. - Supply chain effects: Functional shelf-life at point of use may be shorter than labeled due to manufacturing, quality control, distribution, and mission integration timelines. - Generalizability: Regional differences in formulations/excipients and manufacturer practices can alter labeled shelf-lives; results may not directly translate to specific ISS-stocked brands/generics.