At the stage of commercial production, techno-economic analyses can provide essential insights into areas such as scheduling, vendor contracts, continuous improvement, and process intensification.Analysis of these individual factor sensitivities provide a preliminary framework for understanding expected bounds of manufacturing costs. It can also serve as a prioritization tool for vendor selection when considering larger, multi-material contracts, as well as with research and development efforts. This analysis could be strengthened to include a forecasting capacity in future work by integrating market analyses to weight each level of factor variation with a likelihood based on predictive market data. From this information, one could establish an anticipated range of COGS based on key cost factors to holistically define uncertainty and risk.Within the given parameter range for expression level and yearly production volume, COGS is more strongly impacted by the expression level. This behavior is specific to the defined parameter ranges, which were selected based on anticipated needs and expectations. In this study, we assumed that raw material and consumable resource purchase costs per unit are independent of yearly amount purchased. As yearly production increases, economies of scale dictate that the material unit price will decrease. This becomes a more important consideration when evaluating COGS over a wide yearly production range. Figure 5 shows similar behaviors for changes in total COGS with expression level and yearly production. However,lettuce vertical farming there is a dissimilar behavior in the upstream versus downstream contributions to COGS over the parameter range. Varying expression level largely influences the upstream processing COGS, while varying yearly production largely influences the downstream processing COGS.
The main reason is that the costly downstream operations are economically dependent on AMP quantity rather than on stream composition. Additionally, we chose to conservatively fix AMP recovery in the downstream, regardless of expression level. The low upstream COGS sensitivity to yearly production is because of the approximately linear scalability of the production platform. This is a main advantage of plant-based production that makes the scale-up from lab to commercial scale considerably simpler and faster than traditional bioreactor-based production platforms.As yearly production changes, the upstream processing scales in an approximately linear fashion for a given processing strategy. However, one could anticipate that scaling to even higher yearly production could enable higher efficiency upstream processing strategies and thus improve the scaling dynamics of upstream economic contributions.The nicotine-free S. oleracea scenario provides insight into the manufacturing costs associated with nicotine clearance. There are minor differences in plant growth and harvest operations, but the majority of upstream COGS reduction is because of higher product recovery and thus lower biomass requirements for a given yearly production level. Higher product recovery is attributed to the removal of the nicotine clearance chromatography step present in the N. benthamiana base case scenario, as illustrated in Figure 2. The smaller batch size and simpler downstream processing as compared to the N. benthamiana base case scenario result in a 26% reduction in the downstream cycle time and 37% reduction in downstream labor costs, yielding a COGS of $4.92/g AMP.
The field-grown N. tabacum scenario results in the lowest COGS of $3.00/g AMP, providing reasonable justification to pursue this manufacturing process. However, our assumptions do not account for potential upstream difficulties associated with product expression consistency, greenhouse growth, and transplantation of seedlings or crop loss because of adverse weather events throughout the growing season, nor do they account for the downstream difficulties associated with removal of the more viscous N. tabacum host leaf impurities. Future work to experimentally support key assumptions of field growth could add higher confidence and value to this alternative scenario. Additionally, the current growth strategy is based on tobacco production as a commodity good; there may be a different growth strategy that is optimal for recombinant protein production . It is worth noting that this manufacturing process is expected to scale especially well. In our model, we assume that dedicated personnel and upstream equipment are required for transgenic handling. At an annual production level of 500 kg AMP, this results in 17% upstream equipment utilization. This means that as the yearly production demand increases, we expect marginal increases to upstream CAPEX and OPEX. As such, we expect upstream-related COGS to reduce dramatically with increases in yearly production demand.Biotic food sanitizers can be used in a variety of applications to augment traditional food sanitizing treatments against specific high-risk pathogens. Given the differences in food safety practices among food products, it can be difficult to measure the cost of use as a single value. Instead, we focused our discussion on cost of use calculations with application rates representative of AMP use—colicins for control of E. coli on red meats. We chose to investigate this example at several points along beef processing: animal washing, post-slaughter carcass cleaning, and meat product protection. We anticipate an application rate of 2–10 ppm AMP in water for animal and carcass wash or 2–10 mg AMP per kg meat product. It should be pointed out that, according to the recently published paper of Hahn-Löbmann et al. in 2019, the application rates of salmocins, Salmonella -derived bacteriocins, could be up to 10 times lower because of the higher potency of salmocins.Figure 7 shows the cost of use estimates for select technoeconomic scenarios modeled in this study compared to relevant standard sanitizing treatments.
Cost of use assumptions and a sample calculation of those performed to generate the cost of use estimates can be viewed in Table S7 and Calculation S1, respectively. In all three points of intervention, AMP application cost ranges are below or overlapping those of standard treatments. Additional information is needed on application rates and spray volume used in animal washing to reduce AMP cost of use range and increase confidence in cost comparison to standard treatments. On the other hand, AMP cost of use ranges for treatment of meat product overlap significantly with standard interventions, indicating comparable costs. Finally, the AMP cost of use ranges for post-slaughter carcass cleaning suggest that the use of AMP at this beef processing juncture has the potential to be substantially lower in cost than standard treatments.Current food safety practices, although largely effective, result in food borne illnesses that impose a $14 billion annual burden on the US healthcare system. As the looming prevalence of antibiotic resistance grows, so will the impact of food borne illnesses. The need for protection against food borne pathogens is only increasing. Reports as far back as 20 years ago acknowledge that areas of the food industry like the meat sector will need to absorb additional costs to improve food safety levels.We investigated bacteriophagederived lysins and bacteria-derived AMPs to explore the capacity of this class of biotic sanitizers to improve food safety levels in the costsensitive food industry. Although previous studies illustrate the efficacy of AMPs, in this study, we performed a techno-economic analysis of plant-based production of AMPs to better understand the commercialization potential of products produced using this platform. Our analysis predicts a $6.88/g AMP COGS for the base case scenario, $4.92/g for the nicotine-free S. oleracea scenario, and $3.00/g for the field-grown N. tabacum scenario. We also evaluated the sensitivity of the base case COGS to changes in purchase price, expression level, and yearly production. In doing so, we identified economic “hot spots,” which include the large contribution of the soilless plant substrate and downstream labor-dependent costs . The cost of use analysis indicates that AMPs are projected to de-risk food borne disease in beef processing as supplemental sanitizing treatments at only minor economic perturbation across several key processing junctures. It is expected that other food processing operations would yield similar benefits. This techno-economic analysis of plant-based production of AMPs is focused on manufacturing costs and the implications for application costs. In developing this model and analysis, we have identified several areas of importance for future analysis, for example,vertical grow shelf consideration of avoided costs associated with the prevention of food disease and illness. An example of a major avoided cost is that associated with food recall, which includes impact to brand image and loss of sales. A cost–benefit model that includes these avoided costs may provide more complete insights into AMPs as a food sanitizing treatment. In addition, there are social, cultural, and behavioral factors that can impact food safety that are not considered in this economic analysis. In our analysis, we describe plant-based production of AMPs as a food processing aid.
A direct evaluation of traditional manufacturing platforms, such as mammalian cell suspension culture and bacterial fermentation, as alternative scenarios would be a valuable future contribution. To our knowledge, there are no existing direct comparisons of whole plant, microbial fermentation, and mammalian cell culture platforms in the literature. Future work to compare AMP manufacturing in different locations would also add insight into the geographical and national sensitivity of AMP manufacturing process costs. We compare three host plant batch production models in our analysis, all with different manufacturing processes. A valuable future analysis would be to additionally compare alternative operational modes for a single host plant. Continuous manufacturing is a nascent biotechnology process intensification trend that describes processing of a target molecule from raw materials to final product without any hold steps in a continuous flow process. This contrasts with the more traditional batch manufacturing investigated in this analysis, in which discrete batches are processed at time intervals. It is generally accepted that continuous manufacturing reduces facility footprint, buffer usage, and equipment sizing as compared to batch manufacturing. To date, there are no publications of continuous manufacturing using plant-based production. We anticipate that plant-based production is a favorable platform for continuous manufacturing, which can reduce CAPEX costs through the replacement of large steel vessels with small disposable containers; whole plant production does not require disposable containers, as the plant itself functions as the bioreactor. A techno-economic analysis comparing these two manufacturing modes will provide additional insight into the economics of plant-based production.Potassium is a small, univalent cation that is not toxic in plant cells even at rather high concentrations. Healthy plant cells contain high concentrations of K, but the question is why? What does K do inside the plant? The reason we have these questions about plant K may be because K is small and very mobile in plant cells, making it difficult to pin point its exact roles. The cytoplasm in most healthy plant cells contains over 100 mM K. This is precisely the K concentration needed to promote protein synthesis . Every step of protein synthesis requires over 100 mM K for all of the structures involved to form the correct conformations necessary in the process. Correct structures are extremely important for the interactions of m-RNA, t-RNA, small ribosomes, large ribosomes, and the elongating protein. These structures must have the proper conformations in order to come together and then break apart at the right time. The conformations of these structures and their appropriate activities are only correct when they are bathed in high K concentrations. Similar concentrations of other monovalent cations do not produce the proper conformations. There are over 60 important enzymes that require K-activation in order to reach their maximum catalytic activity, and major processes like protein synthesis and starch synthesis involve some of these enzymes . Interestingly, certain plant species are known for their high K requirements. For example, alfalfa crops has a high K requirement for maximum productivity, removing about 42 lbs K in each ton of hay harvested. In trying to determine the reason for this high K requirement, I considered sugar, starch, protein, and oil production of different crops and compared these factors with K removed by the crop . The only factor highly correlated with K removal was protein removal, supporting the connection between K and protein synthesis discussed above. In fact, this correlation was also high when K and protein contents of grain crops were compared . Therefore, if one is growing a crop that produces large quantities of protein/acre, the K requirement will be high. In addition, the cation, K+ , is required to balance the negative charges of the acidic amino acids, aspartate and glutamate, that extend out from the amino acid polymers. Therefore, there are two important reasons why high protein crops require large quantities of K. Boron is an important micro-nutrient element required for all plant species.