Particles in biopharmaceutical formulations remain a hot topic in drug product development. With new product classes emerging it is crucial to discriminate particulate active pharmaceutical... Show moreParticles in biopharmaceutical formulations remain a hot topic in drug product development. With new product classes emerging it is crucial to discriminate particulate active pharmaceutical ingredients from particulate impurities. Technical improvements, new analytical developments and emerging tools (e.g., machine learning tools) increase the amount of information generated for particles. For a proper interpretation and judgment of the generated data a thorough understanding of the measurement principle, suitable application fields and potential limitations and pitfalls is required. Our review provides a comprehensive overview of novel particle analysis techniques emerging in the last decade for particulate impurities in therapeutic protein formulations (protein-related, excipient-related and primary packaging material-related), as well as particulate biopharmaceutical formulations (virus particles, virus-like particles, lipid nanoparticles and cell-based medicinal products). In addition, we review the literature on applications, describe specific analytical approaches and illustrate advantages and drawbacks of currently available techniques for particulate biopharmaceutical formulations. Show less
Purpose Assessing impacts of abiotic resource use has been a topic of persistent debate among life cycle impact assessment (LCIA) method developers and a source of confusion for life cycle... Show morePurpose Assessing impacts of abiotic resource use has been a topic of persistent debate among life cycle impact assessment (LCIA) method developers and a source of confusion for life cycle assessment (LCA) practitioners considering the different interpretations of the safeguard subject for mineral resources and the resulting variety of LCIA methods to choose from. Based on the review and assessment of 27 existing LCIA methods, accomplished in the first part of this paper series (Sonderegger et al. 2020), this paper provides recommendations regarding the application-dependent use of existing methods and areas for future method development. Method Within the "global guidance for LCIA indicators and methods" project of the Life Cycle Initiative hosted by UN Environment, 62 members of the "task force mineral resources" representing different stakeholders discussed the strengths and limitations of existing LCIA methods and developed initial conclusions. These were used by a subgroup of eight members at the Pellston Workshop (R) held in Valencia, Spain, to derive recommendations on the application-dependent use and future development of impact assessment methods. Results and discussion First, the safeguard subject for mineral resources within the area of protection (AoP) natural resources was defined. Subsequently, seven key questions regarding the consequences of mineral resource use were formulated, grouped into "inside-out" related questions (i.e., current resource use leading to changes in opportunities for future users to use resources) and "outside-in" related questions (i.e., potential restrictions of resource availability for current resource users). Existing LCIA methods were assigned to these questions, and seven methods (ADP(ultimate reserves), SOPURR, LIME2(endpoint), CEENE, ADP(economic reserves), ESSENZ, and GeoPolRisk) are recommended for use in current LCA studies at different levels of recommendation. All 27 identified LCIA methods were tested on an LCA case study of an electric vehicle, and yielded divergent results due to their modeling of impact mechanisms that address different questions related to mineral resource use. Besides method-specific recommendations, we recommend that all methods increase the number of minerals covered, regularly update their characterization factors, and consider the inclusion of secondary resources and anthropogenic stocks. Furthermore, the concept of dissipative resource use should be defined and integrated in future method developments. Conclusion In an international consensus-finding process, the current challenges of assessing impacts of resource use in LCA have been addressed by defining the safeguard subject for mineral resources, formulating key questions related to this safeguard subject, recommending existing LCIA methods in relation to these questions, and highlighting areas for future method development. Show less
Purpose The safeguard subject of the Area of Protection "natural Resources," particularly regarding mineral resources, has long been debated. Consequently, a variety of life cycle impact assessment... Show morePurpose The safeguard subject of the Area of Protection "natural Resources," particularly regarding mineral resources, has long been debated. Consequently, a variety of life cycle impact assessment methods based on different concepts are available. The Life Cycle Initiative, hosted by the UN Environment, established an expert task force on "Mineral Resources" to review existing methods (this article) and provide guidance for application-dependent use of the methods and recommendations for further methodological development (Berger et al. in Int J Life Cycle Assess, 2020). Methods Starting in 2017, the task force developed a white paper, which served as its main input to a SETAC Pellston Workshop (R) in June 2018, in which a sub-group of the task force members developed recommendations for assessing impacts of mineral resource use in LCA. This article, based mainly on the white paper and pre-workshop discussions, presents a thorough review of 27 different life cycle impact assessment methods for mineral resource use in the "natural resources" area of protection. The methods are categorized according to their basic impact mechanisms, described and compared, and assessed against a comprehensive set of criteria. Results and discussion Four method categories have been identified and their underlying concepts are described based on existing literature: depletion methods, future efforts methods, thermodynamic accounting methods, and supply risk methods. While we consider depletion and future efforts methods more "traditional" life cycle impact assessment methods, thermodynamic accounting and supply risk methods are rather providing complementary information. Within each method category, differences between methods are discussed in detail, which allows for further sub-categorization and better understanding of what the methods actually assess. Conclusions We provide a thorough review of existing life cycle impact assessment methods addressing impacts of mineral resource use, covering a broad overview of basic impact mechanisms to a detailed discussion of method-specific modeling. This supports a better understanding of what the methods actually assess and highlights their strengths and limitations. Building on these insights, Berger et al. (Int J Life Cycle Assess, 2020) provide recommendations for application-dependent use of the methods, along with recommendations for further methodological development. Show less
