Sustainability in the biopharmaceutical industry: seeking a holistic perspective

Biopharmaceuticals manufacturing is a critical component of the modern healthcare system, with emerging new treatments composed of increasingly complex biomolecules offering solutions to chronic and debilitating disorders. While this sector continues to grow, it strongly exhibits “boom-to-bust” performance which threatens its long-term viability. Future trends within the industry indicate a shift towards continuous production systems using single use technologies that raises sustainability issues, yet research in this area is sparse and lacks consideration of the complex interactions between environmental, social and economic concerns. The authors outline a sustainability-focused vision and propose opportunities for research to aid the development of a more integrated approach that would enhance the sustainability of the industry

A comparison of the solvation power of the green solvent 2,2,5,5-tetramethyloxolane versus toluene via partition coefficients

2,2,5,5-tetramethyloxolane [previously published as 2,2,5,5-tetramethyltetrahydrofuran (TMTHF)] has recently been demonstrated as a greener and cleaner alternative to toluene in several applications. Assessing similarities in properties of toluene and 2,2,5,5-tetramethyloxolane is crucial for establishing this molecules potential to replace traditional non-polar organic solvents in the cleaner production of chemicals and materials. However, the Hansen solubility parameters (HSP) and Kamlet-Taft parameters (KT) give conflicting views on their similarities and differences, which necessitates a full comparative characterisation of the solvation environment of these two solvents. Such comparisons have been achieved through a direct and extensive determination of partition coefficients between each of the two solvents and water. The partition coefficients and Abraham's solvation parameter model have quantitatively clarified the similarities and differences in properties of 2,2,5,5-tetramethyloxolane and toluene. Solutes of high dipolarity and hydrogen-bond accepting ability tended to favour the aqueous phase in both systems, while large molar volume and high refractive indices favoured the organic phase. A significant difference between 2,2,5,5-tetramethyloxolane and toluene was observed for hydrogen-bond donating solutes. In general, such solutes strongly preferred the aqueous phase in the toluene/water system but preferred the organic phase in the 2,2,5,5-tetramethyloxolane/water system. This was due to the interaction of the protic solutes with the lone pairs of electrons on the ethereal oxygen of 2,2,5,5-tetramethyloxolane, a feature that is not present on toluene, and opens up new possibilities for applications of this sustainable solvent in liquid-liquid extraction, particularly in the isolation of natural products. As toluene is such an important solvent in the chemical industry, its replacement with a greener alternative such as 2,2,5,5-tetramethyloxolane would be hugely significant for cleaner synthesis, extractions and separations

Financial inclusion among social housing tenants

This research report examines access to and use of mainstream and alternative financial services by social housing residents in Ireland, with a focus on savings and credit

Challenges in the development of bio-based solvents : A case study on methyl(2,2-dimethyl-1,3-dioxolan-4-yl)methyl carbonate as an alternative aprotic solvent

Many traditional solvents have drawbacks including sustainability and toxicity issues. Legislations such as REACH is driving the move towards less hazardous chemicals and production processes. Therefore, safer bio-based solvents need to be developed. Herein, a 10 step method has been proposed for the development of new bio-based solvents that utilise a combination of in silico modelling of Hansen solubility parameters (HSPs), experimental Kamlet-Abboud-Taft parameters, selection of green synthetic routes followed by applications testing and toxicity measurements. The challenges that the chemical industry face in the development of new bio-based solvents are highlighted through a case study on methyl (2,2-dimethyl-1,3-dioxolan-4-yl) methyl carbonate (MMC) which can be synthesised from glycerol. Although MMC is an attractive candidate as a replacement solvent, simply being bio-derived is not enough for a molecule to be regarded as green. The methodology of solvent development described here is a broadly applicable protocol that will indicate if a new bio-based solvent is functionally proficient, but will also highlight the importance of early stage Kamlet-Abboud-Taft parameters determination and toxicity testing in the development of a green solvent

Thermal Upgrade of Enzymatically Synthesized Aliphatic and Aromatic Oligoesters

The enzymatic synthesis of polyesters in solventless systems is an environmentally friendly and sustainable method for synthetizing bio-derived materials. Despite the greenness of the technique, in most cases only short oligoesters are obtained, with limited practical applications or requiring further chemical processing for their elongation. In this work, we present a catalyst-free thermal upgrade of enzymatically synthesized oligoesters. Dierent aliphatic and aromatic oligoesters were synthesized using immobilized Candida antarctica lipase B (iCaLB) as the catalyst (70 C, 24 h) yielding poly(1,4-butylene adipate) (PBA, Mw = 2200), poly(1,4-butylene isophthalate) (PBI, Mw = 1000), poly(1,4-butylene 2,5-furandicarboxylate) (PBF, Mw = 600), and poly(1,4-butylene 2,4-pyridinedicarboxylate) (PBP, Mw = 1000). These polyesters were successfully thermally treated to obtain an increase in Mw of 8.5, 2.6, 3.3, and 2.7 folds, respectively. This investigation focused on the most successful upgrade, poly(1,4-butylene adipate), then discussed the possible eect of di-ester monomers as compared to di-acids in the thermally driven polycondensation. The herein-described two-step synthesis method represents a practical and cost-eective way to synthesize higher-molecular-weight polymers without the use of toxic metal catalysts such as titanium(IV) tert-butoxide, tin(II) 2-ethylhexanoate, and in particular, antimony(IV) oxide. At the same time, the method allows for the extension of the number of reuses of the biocatalyst by preventing its exposure to extreme denaturating conditions

A Natural, Calcium-rich Marine Multi-material Complex Preserves Bone Structure, Composition and Strength in an Ovariectomized Rat Model of Osteoporosis

Calcium supplements are used as an aid in the prevention of osteopenia and osteoporosis and also for the treatment of patients when used along with medication. Many of these supplements are calcium carbonate based. This study compared a calcium-rich, marine multi-mineral complex (Aquamin) to calcium carbonate in an ovariectomised rat model of osteoporosis in order to assess Aquamin’s efficacy in preventing the onset of bone loss. Animals were randomly assigned to either non-ovariectomy control (Control), ovariectomy (OVX) plus calcium carbonate, ovariectomy plus Aquamin or ovariectomy plus Aquamin delay where Aquamin treatment started 8 weeks post OVX. At the end of the 20-week study, the trabecular architecture was measured using micro computed tomography, bone composition was assessed using Fourier transform infrared spectroscopy and the mechanical properties were assessed using nanoindentation and three-point bend testing. The study demonstrates that oral ingestion of Aquamin results in less deterioration of trabecular bone structure, mineral composition and tissue level biomechanical properties in the tibia of rats following ovariectomy than calcium carbonate. This study has shown that in an animal model of osteoporosis, Aquamin is superior to calcium carbonate at slowing down the onset of bone loss

A Natural Calcium-rich Multi-mineral Complex Preserves Bones Structure, Composition and Strength in an Ovariectomized Rat Model of Osteoporosis

Calcium supplements are used as an aid in the prevention of osteopenia and osteoporosis and also for the treatment of patients when used along with medication. Many of these supplements are calcium carbonate based. This study compared a calcium-rich, marine multi-mineral complex (Aquamin) to calcium carbonate in an ovariectomised rat model of osteoporosis in order to assess Aquamin’s efficacy in preventing the onset of bone loss. Animals were randomly assigned to either non-ovariectomy control (Control), ovariectomy (OVX) plus calcium carbonate, ovariectomy plus Aquamin or ovariectomy plus Aquamin delay where Aquamin treatment started 8 weeks post OVX. At the end of the 20-week study, the trabecular architecture was measured using micro computed tomography, bone composition was assessed using Fourier transform infrared spectroscopy and the mechanical properties were assessed using nanoindentation and three-point bend testing. The study demonstrates that oral ingestion of Aquamin results in less deterioration of trabecular bone structure, mineral composition and tissue level biomechanical properties in the tibia of rats following ovariectomy than calcium carbonate. This study has shown that in an animal model of osteoporosis, Aquamin is superior to calcium carbonate at slowing down the onset of bone loss

Greenness Assessment and Synthesis for the Bio-Based Production of the Solvent 2,2,5,5-Tetramethyloxolane (TMO)

2,2,5,5-tetramethyloxolane (TMO) has recently been identified and demonstrated as a safer solvent to replace toluene, THF, and hydrocarbons in a handful of applications. Herein, several bio-based routes to TMO are presented and assessed for greenness, assisted by the CHEM21 Metrics Toolkit and BioLogicTool plots. Using glucose as a common starting point, two chemocatalytic routes and two biochemical routes to TMO were identified and the pathways compared using the aforementioned tools. In addition, bio-based TMO was synthesised via one of these routes; from methyl levulinate supplied by Avantium, a by-product of the sugar dehydration step during the production of 2,5-furandicarboxylic acid. First, methyl levulinate underwent triple methylation using methyl magnesium chloride (MeMgCl) to yield 2,5-dimethylhexane-2,5-diol (DHL) in high yields of 89.7%. Then DHL was converted to high purity TMO (>98.5%) by cyclodehydration using H-BEA zeolites based on the previously reported approach. Bio-based content of this TMO was confirmed by ASTM D6866-20 Method B and found to have 64% bio-based carbon, well above the threshold of 25% set by CEN/TC 411 standards and matching the anticipated content. This study represents the first demonstration of a bio-based synthesis of TMO and confirmation of bio-content by accepted standards