| Summary: | The <i>aim</i> of this work is the development of a methodology for the technical and environmental assessment of biowaste valorization in 2G biorefineries. Italy was chosen as case study, considering years 2016−2017. <i>Approach</i>: the Italian context was evaluated through the following key parameters: Gross domestic power, climate, demography, and population density distribution described the Italian framework. The four most abundant biowaste categories were defined through their amounts and geo-localization: wastewater and sewage sludge (WSS, 4.06 Mt/y), organic fraction of municipal solid waste (OFMSW, 1.7 Mt/y), agricultural livestock waste (ALW, 5.7 Mt/y), and waste deriving from the food industry (FIW, 2.6 Mt/y). The geo-localization and quantitative evaluations of the available biowaste amounts were aimed at defining the dimension and localization of the biorefinery plant and at optimizing supply and transport chains, while the qualitative characteristic were aimed to evaluate the most promising process among thermo-valorization (TH) and anaerobic digestion (AD). <i>Results:</i> All considered biowastes were appropriate for biorefinery processes, since carbon content exceeds 40% and the carbon−nitrogen ratio was between 10 and 30. All biowaste categories were evaluated as feedstocks for two biorefinery processes: anaerobic digestion (AD) and thermo-valorization (TH) with energy recovery. Compared to TH, AD achieved in all cases the best performances in terms of produced energy and avoided CO<sub>2</sub> emissions. The primary energy production of AD and TH for WSS, OFMSW, ALW, and FIW were respectively: 7.89 vs. 2.4 kWh/kg; 8.7 vs. 2.6 kWh/kg; 10.85 vs. 5.5 kWh/kg; and 12.5 vs. 7.8 kWh/kg. The <i>main findings</i> of this work were: the adoption of AD was technically more suitable than TH; AD increased the avoided CO<sub>2</sub> emissions of 10%−89.9% depending on biowaste category.
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