A roadmap for model-based bioprocess development.

The bioprocessing industry is undergoing a significant transformation in its approach to quality assurance, shifting from the traditional Quality by Testing (QbT) to Quality by Design (QbD). QbD, a systematic approach to quality in process development, integrates quality into process design and control, guided by regulatory frameworks. This paradigm shift enables increased operational efficiencies, reduced market time, and ensures product consistency. The implementation of QbD is framed around key elements such as defining the Quality Target Product Profile (QTPPs), identifying Critical Quality Attributes (CQAs), developing Design Spaces (DS), establishing Control Strategies (CS), and maintaining continual improvement. The present critical analysis delves into the intricacies of each element, emphasizing their role in ensuring consistent product quality and regulatory compliance. The integration of Industry 4.0 and 5.0 technologies, including Artificial Intelligence (AI), Machine Learning (ML), Internet of Things (IoT), and Digital Twins (DTs), is significantly transforming the bioprocessing industry. These innovations enable real-time data analysis, predictive modelling, and process optimization, which are crucial elements in QbD implementation. Among these, the concept of DTs is notable for its ability to facilitate bi-directional data communication and enable real-time adjustments and therefore optimize processes. DTs, however, face implementation challenges such as system integration, data security, and hardware-software compatibility. These challenges are being addressed through advancements in AI, Virtual Reality/ Augmented Reality (VR/AR), and improved communication technologies. Central to the functioning of DTs is the development and application of various models of differing types - mechanistic, empirical, and hybrid. These models serve as the intellectual backbone of DTs, providing a framework for interpreting and predicting the behaviour of their physical counterparts. The choice and development of these models are vital for the accuracy and efficacy of DTs, enabling them to mirror and predict the real-time dynamics of bioprocessing systems. Complementing these models, advancements in data collection technologies, such as free-floating wireless sensors and spectroscopic sensors, enhance the monitoring and control capabilities of DTs, providing a more comprehensive and nuanced understanding of the bioprocessing environment. This review offers a critical analysis of the prevailing trends in model-based bioprocessing development within the sector.

Design and Development of an Edible Coating for a Ready-to-Eat Fish Product.

The application of chitosan and alginate coatings for a ready-to-eat (RTE) baked fish product was studied. An experimental design was used to investigate the effect of coating a polysaccharide concentration and glycerol addition on the safety (microbial growth) and quality (water loss and lipid oxidation) of an RTE fish product under optimal and abused storage conditions. The results showed that a chitosan coating with 1% (w/v) chitosan in 1% (v/v) acetic acid and 15% (w/w chitosan) glycerol, or a 1% (w/v) alginate coating with no glycerol and no crosslinking, showed the best performance in controlling the tested safety and quality parameters. The desirability method was used to identify the shelf lives of chitosan, alginate, and double-coated RTE products. The chitosan-coated samples showed the best performance with a three-fold shelf-life extension compared to the uncoated products stored at 4 °C. Moreover, the tested coatings demonstrated their ability to provide protective functions under abused storage conditions. These results strongly suggest that edible coatings have significant potential in enhancing the shelf life and safety of ready-to-eat (RTE) fish products.

A multi-purpose pilot-scale molten metal & molten salt pyrolysis reactor.

This paper describes the design features and operational details of a molten metal pyrolysis reactor. Such a reactor allows pyrolysis experimentation on biomass, aluminium-laminated plastics, mixed plastics, carbon fibre materials, etc. Experimental results on biodegradable plastic, carbon fibre composites, biomass and printed circuit boards (PCBs) are presented.•The inner container can have a sloped or flat-bottom depending on the material.•The method can be used to pyrolyse composite and pure materials.

Recycling of aluminium laminated pouches and Tetra Pak cartons by molten metal pyrolysis - Pilot-scale experiments and economic analysis.

Aluminium laminated (AL) pouch packages and aluminium laminated Tetra-Pak cartons are considered unrecyclable, reducing their otherwise excellent lifecycle performance. This paper describes experimental results on pilot plant trials to recycle AL packages with a molten metal pyrolysis reactor. The experimental evidence shows that both package formats can be recycled and that clean aluminium can be recovered. However, the recovered aluminium from Al pouches may require mechanical cleaning as the consumer's information is printed onto the aluminium, leaving a carbon residue on the recovered aluminium. On the other hand, over 90% of the polypropylene plastic layer on the AL packaging pyrolysed into waxes, pointing to excellent kinetics. Moreover, an economic analysis of a 4,000 t/y commercial-scale plant demonstrates that a molten metal AL recycling plant is economically viable, achieving an internal rate of return (IRR) of over 20%.

Economic assessment of a 40,000 t/y mixed plastic waste pyrolysis plant using direct heat treatment with molten metal: A case study of a plant located in Belgium.

Pyrolysis has been identified as an ideal process to recycle mixed plastic waste (MPW). This study investigates the economics of a 40,000 t/y MPW pyrolysis process, called PlastPyro, located in Belgium, to an accuracy of ±15% i.e. "Definite Estimate". The process uses molten metal in a direct heat treatment process to pyrolyse the waste. An internal rate of return (IRR) of 20% strongly indicates that a 40,000 t/y PlastPyro plant is financially attractive for private investors. The capital expenditure (CAPEX) is estimated to be €20.1 m or €26.1 m if the cost of capital is included. The operating expenditures (OPEX) of the plant are estimated €3.4 m per year. The sensitivity analysis shows six main variables having major impacts on the financial returns of a PlastPyro plant: (1) the addressable volume and quality of plastic waste, (2) the feedstock costs, (3) the capital and operating expenditures, (4) the revenues from the sale of the produced pyrolysis oil (P-oil), (5) the tipping fees and (6) the potential to co-locate a PlastPyro plant with a waste plastic sorting facility. For example, the 15-year low P-oil revenue price of €210/t results in an IRR of 20%; but on the 6th of March 2020 the P-oil price may have achieved €227/t, resulting in an IRR of 37%. The paper also shows that a reliable supply of MPW is available, and that reliable, accessible markets for the P-oil are available. Finally, cost estimates should state their accuracy and usually factorial cost estimates are not accurate enough to state the IRR.

Biotechnological approaches for the production of natural colorants by Talaromyces/Penicillium: A review.

There has been an increased interest in replacing synthetic colorants by colorants obtained from natural sources, especially microbial pigments. Monascus pigments have been used as natural colorings and food additives in Asia for centuries but have raised toxicity issues. Recently, Talaromyces/Penicillium species have been recognized as potential strains to produce natural pigments similar to those produced by Monascus species. To date, it has not been published a literature compilation about the research and development activity of Talaromyces/Penicillium pigments. Developing a new bioprocess requires several steps, from an initial concept to a practical and feasible application. Industrial applications of fungal pigments will depend on: (i) characterization of the molecules to assure a safe consumption, (ii) stability of the pigments to the processing conditions required by the products where they will be incorporated, (iii) optimizing process conditions to achieve high yields, iv) implementing an efficient product recovery and (v) scale-up of the bioprocess. The above aspects have been reviewed in detail to evaluate the feasibility of reaching a commercial scale of the pigments produced by Talaromyces/Penicillium. Finally, the biological activities of the pigments and their potential applications are discussed.

Selection of best conditions of inoculum preparation for optimum performance of the pigment production process by Talaromyces spp. using the Taguchi method.

Process optimisation techniques increasingly need to be used early on in research and development of processes for new ingredients. There are different approaches and this article illustrates the main issues at stake with a method that is an industry best practice, the Taguchi method, suggesting a procedure to assess the potential impact of its drawbacks. The Taguchi method has been widely used in various industrial sectors because it minimises the experimental requirements to define an optimum region of operation, which is particularly relevant when minimising variability is a target. However, it also has drawbacks, especially the intricate confoundings generated by the experimental designs used. This work reports a process optimisation of the synthesis of red pigments by a fungal strain, Talaromyces spp. using the Taguchi methodology and proposes an approach to assess from validation trials whether the conclusions can be accepted with confidence. The work focused on optimising the inoculum characteristics, and the studied factors were spore age and concentration, agitation speed and incubation time. It was concluded that spore age was the most important factor for both responses, with optimum results at 5 days old, with the best other conditions being spores concentration, 100,000 (spores/mL); agitation, 200 rpm; and incubation time, 84 h. The interactive effects can be considered negligible and therefore this is an example where a simple experimental design approach was successful in speedily indicating conditions able to increase pigment production by 63% compared to an average choice of settings. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:621-632, 2017.

Perstraction of Intracellular Pigments through Submerged Fermentation of Talaromyces spp. in a Surfactant Rich Media: A Novel Approach for Enhanced Pigment Recovery.

A high percentage of the pigments produced by Talaromyces spp. remains inside the cell, which could lead to a high product concentration inhibition. To overcome this issue an extractive fermentation process, perstraction, was suggested, which involves the extraction of the intracellular products out of the cell by using a two-phase system during the fermentation. The present work studied the effect of various surfactants on secretion of intracellular pigments produced by Talaromyces spp. in submerged fermentation. Surfactants used were: non-ionic surfactants (Tween 80, Span 20 and Triton X-100) and a polyethylene glycerol polymer 8000, at different concentrations (5, 20, 35 g/L). The highest extracellular pigment yield (16 OD500nm) was reached using Triton X-100 (35 g/L), which was 44% higher than the control (no surfactant added). The effect of addition time of the selected surfactant was further studied. The highest extracellular pigment concentration (22 OD500nm) was achieved when the surfactant was added at 120 h of fermentation. Kinetics of extracellular and intracellular pigments were examined. Total pigment at the end of the fermentation using Triton X-100 was 27.7% higher than the control, confirming that the use of surfactants partially alleviated the product inhibition during the pigment production culture.

Assessment of the Dyeing Properties of the Pigments Produced by Talaromyces spp.

The high production yields of pigments by Talaromyces spp. and their high thermal stability have implied that industrial application interests may emerge in the food and textile industries, as they both involve subjecting the colourants to high temperatures. The present study aimed to assess the potential application of the pigments produced by Talaromyces spp. in the textile area by studying their dyeing properties. Dyeing studies were performed on wool. The dyeing process consisted of three stages: scouring, mordanting, and dyeing. Two different mordants (alum, A; ferric chloride, F) were tested at different concentrations on fabric weight (A: 5, 10, 15%; F: 10, 20, 30%). The mordanting process had a significant effect on the final colour of the dyed fabrics obtained. The values of dyeing rate constant (k), half-time of dyeing (t1/2), and sorption kinetics behaviour were evaluated and discussed. The obtained results showed that pigments produced by Talaromyces spp. could serve as a source for the natural dyeing of wool textiles.

Scrap tyre recycling process with molten zinc as direct heat transfer and solids separation fluid: A new reactor concept.

Every year about 1.5 billion tyres are discarded worldwide representing a large amount of solid waste, but also a largely untapped source of raw materials. The objective of the method was to prove the concept of a novel scrap tyre recycling process which uses molten zinc as the direct heat transfer fluid and, simultaneously, uses this media to separate the solids products (i.e. steel and rCB) in a sink-float separation at an operating temperature of 450-470 °C. This methodology involved: •construction of the laboratory scale batch reactor,•separation of floating rCB from the zinc,•recovery of the steel from the bottom of the reactor following pyrolysis.

Novel waste printed circuit board recycling process with molten salt.

The objective of the method was to prove the concept of a novel waste PCBs recycling process which uses inert, stable molten salts as the direct heat transfer fluid and, simultaneously, uses this molten salt to separate the metal products in either liquid (solder, zinc, tin, lead, etc.) or solid (copper, gold, steel, palladium, etc.) form at the operating temperatures of 450-470 °C. The PCB recovery reactor is essentially a U-shaped reactor with the molten salt providing a continuous fluid, allowing molten salt access from different depths for metal recovery. A laboratory scale batch reactor was constructed using 316L as suitable construction material. For safety reasons, the inert, stable LiCl-KCl molten salts were used as direct heat transfer fluid. Recovered materials were washed with hot water to remove residual salt before metal recovery assessment. The impact of this work was to show metal separation using molten salts in one single unit, by using this novel reactor methodology. •The reactor is a U-shaped reactor filled with a continuous liquid with a sloped bottom representing a novel reactor concept.•This method uses large PCB pieces instead of shredded PCBs as the reactor volume is 2.2 L.•The treated PCBs can be removed via leg B while the process is on-going.