(M1330-09-60) Sustainability Considerations in Patient-Centric Formulation Selection

Purpose: In pursuit of ensuring drug safety and effectiveness, patient-centricity has become a cornerstone of modern drug development. Both the pharmaceutical industry and regulatory agencies aim to integrate patient’s perspective; needs, preferences and limitations early into drug product design process [1, 2]. While sustainability impact, as part of drug development ultimately impacting patients, is recognized in literature as a relevant factor in drug development [3], its integration into patient-centric formulation design remains limited. This work explores how sustainability considerations can be systematically incorporated into patient-centric formulation selection to support decision-making process.

Methods: The assessment focused solely on representations of common formulations for systemic drug delivery, not considering custom administration routes or accounting for production of the drug substance. The carbon dioxide equivalent (kg CO₂e) was used to represent a comparator metric for various sustainability aspects, including cost, energy consumption, waste disposal, and emissions. Based on Product Life Cycle Accounting and Reporting Standard [4], the analysis considered published data on CO₂e contribution from (for formulation commonly required) excipients, formulation manufacturing, primary and secondary packaging material [5], formulation package distribution and storage, as well as end-of-life disposal [5, 6]. To enable direct comparison of 25 formulations, normalizing the data by the usual number of doses per formulation package, as well as by administration frequency (weekly usage) was explored.

Results: Based on an example of calculated CO₂e values per formulation package, estimated equivalent of carbon emission varied across 25 assessed formulation types. Common formulations, like oral tablets or topical creams, exhibited relatively low CO₂e per package ( < 0,4 kg CO₂e). In contrast, complex formulations, such inhalers and infusions, showed significantly (up to 70-fold) higher CO₂e values. Normalizing emissions by the number of doses per formulation package revealed that multi-dose formats (e.g. inhalers with 200 actuations) were more efficient per dose. On the other hand, high frequency of use amplified the environmental impact of single-use formulations, particularly of ones with substantial packaging waste, e.g. subcutaneous injections. Additionally, formulations requiring energy-intensive manufacturing process (e.g. sterilization or aseptic filling for intravenous use) were associated with a higher CO₂e.
Figure 1. depicts an estimated distribution of CO₂e per formulation over the range of usual administration frequency. Overall, small, compact, multi-dose formulations had lower CO₂e compared to single-use, or high-volume formulations with bulky and heavy packaging (e.g. oral solutions and suspensions).

Conclusion: Understanding patient needs, requirements, preferences, and limitations remains essential for appropriate administration route and formulation selection. Patient-centricity should serve as the core starting point for formulation selection, and only once equivalent or comparable formulations are identified from this perspective, can sustainability considerations be a meaningfully add-on supporting decision-making process. This assessment demonstrated that CO₂e can be a suitable metric for sustainability comparison between formulations, influenced by factors such as dose quantity, administration frequency, and packaging. Smaller, lighter, and simpler multi-dose formulations generally exhibit higher sustainability and can be the preferred choice if multiple patient-centric formulations are being considered for development. A CO₂e evaluation, encompassing material sourcing, manufacturing, packaging, distribution, storage, and disposal, can support more sustainable formulation choices, ensuring more patient-centricity at the beginning of the drug product design and development process. Nevertheless, the analysis is limited by the availability of standardized data on carbon emissions across the pharmaceutical supply chain. In addition to the presented assessment, the duration of therapy (acute vs. chronic) should be considered on a case-by-case basis, as it will stay drug- and indication-specific. This may ensure a better and more accurate comparison between the considered formulations.

References: [1] Stegeman et al. AAPS J, 2016; 18(5):1047-1055
[2] Algorri et al. J Pharm Sci, 2023; 112(4):922-936
[3] Singh et al. Clin Transl Sci, 2025; 18(5):e70241
[4] Greenhouse Gas Protocol, 2013; Product Life Cycle Accounting and Reporting Standard
[5] Ministry of Economics and Finance (France), 2025; Carbon footprint of medicines: Assessment methodology
[6] Greenhouse Gas Protocol, 2022; Appendix D: Calculation formula summary tables

Figure 1. Distribution of carbon dioxide emission equivalent for assessed formulations normalized by a dose number per package, as well as by an estimated administration frequency span