Enhancing Food Safety, Quality and Sustainability Through Biopesticide Production Under the Concept of Process Intensification

Abstract

The worldwide population is anticipated to reach 10.12 billion by the year 2100, thereby amplifying the necessity for sustainable agricultural methodologies to secure food availability while reducing ecological consequences. Conventional synthetic pesticides, while capable of increasing crop yields by as much as 50%, present considerable hazards such as toxicity, the emergence of resistance, and environmental pollution. This review examines biopesticides, originating from microbial (e.g., Bacillus thuringiensis, Trichoderma spp.), plant, or animal sources, as environmentally sustainable alternatives which address pest control through mechanisms including antibiosis, hyperparasitism, and competition. Biopesticides provide advantages such as biodegradability, minimal toxicity to non-target organisms, and a lower likelihood of resistance development. The global market for biopesticides is projected to be valued between USD 8 and 10 billion by 2025, accounting for 3–4% of the overall pesticide sector, and is expected to grow at a compound annual growth rate (CAGR) of 12–16%. To mitigate production costs, agro-industrial byproducts such as rice husk and starch wastewater can be utilized as economical substrates in both solid-state and submerged fermentation processes, which may lead to a reduction in expenses ranging from 35% to 59%. Strategies for process intensification, such as the implementation of intensified bioreactors, continuous cultivation methods, and artificial intelligence (AI)-driven monitoring systems, significantly improve the upstream stages (including strain development and fermentation), downstream processes (such as purification and drying), and formulation phases. These advancements result in enhanced productivity, reduced energy consumption, and greater product stability. Patent activity, exemplified by 2371 documents from 1982 to 2021, highlights advancements in formulations and microbial strains. The integration of circular economy principles in biopesticide production through process intensification enhances the safety, quality, and sustainability of food systems. Projections suggest that by the 2040s to 2050s, biopesticides may achieve market parity with synthetic alternatives. Obstacles encompass the alignment of regulations and the ability to scale in order to completely achieve these benefits.

1. Introduction

The global population is continuously increasing and is projected to attain 10.12 billion individuals by the end of the 21st century [1]. In recent years, this rise has led to the extensive application of synthetic pesticides aimed at safeguarding crops and ensuring substantial food production to meet the needs of the population [2,3]. Elevated yields of food crops are contingent upon the utilization of enhanced varieties, effective disease management strategies, and appropriate fertilization practices. Over time, the application of pesticides has become essential in agricultural practices, as approximately 30% of agricultural produce is lost to pest infestations [1]. Nevertheless, there are a number of drawbacks to using synthetic pesticides, including as toxicity, poisoning, environmental pollution, and increased expenses [4]. Unfortunately, chemical pesticide resistance is becoming more common.

Some fungi play an important role in pest management, and biological control agents like these are gradually replacing traditional chemical pesticides [5,6]. Products made from natural components are easily biodegradable; thus, their use is sustainable and environmentally friendly [4,5,7,8]. Their effectiveness is demonstrated at low concentrations, and they are designed to target certain insect species exclusively [9]. When it comes to reducing crop loss, biopesticides are a cost-effective and effective option [5,8].

Microorganisms or natural chemicals are the fundamental components of biopesticides, which are used to control plant diseases. Their use in organic and conventional farming practices is based on whether they originate from microbes, plants, or animals [8,9,10]. Biopesticides are derived from plants and microbes because these sources contain high concentrations of bioactive and antimicrobial chemicals [4,7,8]. These compounds include phenols, oils, quinones, alkaloids, terpenes, proteins, and nitrogen-rich peptides. Microbes use a wide variety of strategies to get rid of certain pests. The main ways in which they work are through competition, hyperparasitism, antibiosis, synergism, and the release of volatile chemicals [4,11]. Managing plant diseases, weeds, and insect pests has made use of these [9]. Species of fungus and bacteria such as Trichoderma and Beauveria, as well as bacterial species including Pseudomonas, Bacillus and Serratia, have all shown promise as biocontrol agents. Still, almost 97% of the biopesticide industry is occupied by Bacillus thuringiensis biopesticides [12,13]. B. thuringiensis produces crystals of a protein that kills insects of the Coleoptera, Diptera, and Lepidoptera orders [2,10]. On the other hand, Trichoderma spp. is a filamentous fungus that has been studied extensively for its ability to combat diverse crop phytopathogens. Countless investigations have shown its usefulness [9]. According to reports, T. harzianum has an antagonistic impact on Fusarium, Rhizoctonia and Pythium [5,9]. It is possible to combine these antagonistic activities in a way that enhances their efficacy.

The market for biopesticides is categorized into bioinsecticides, bioherbicides, and biofungicides, accounting for approximately USD 2.5 billion of global pesticide consumption [14,15]. The production of biopesticides from microorganisms may incur significant costs due to the reliance on synthetic media. Consequently, research has focused on identifying alternatives to mitigate these expenses. One promising approach involves utilizing by-products as substrates for various microbial strains employed in biopesticide production, which has the potential to decrease costs by 35–59% [16]. Consequently, the utilization of diverse by-products from agricultural practices has been documented in the cultivation of microorganisms utilized in biocontrol methods. Numerous studies have documented the production of biopesticides through solid-state fermentation (SSF) and liquid-state fermentation (LSF). For instance, the utilization of rice husk for growing B. bassiana and T. harzianum via SSF has been highlighted [17]. Additionally, wastewater from the starch industry has been employed for the production of biopesticides using B. thuringiensis [2,18].

Based on the critical analysis outlined in the paragraphs that came in previous section, which relies on the current published scientific literature, there are discernible research gaps that necessitate prompt attention for the advancement of human welfare and the innovative endeavors undertaken by scientists and researchers globally. Considering the important aspects discussed in previous paragraphs, it is crucial to address the topic at hand. As a result, this review article has been formulated.

It is important to conduct a thorough assessment of the environmental, health, and economic constraints associated with synthetic pesticides in contemporary agriculture while emphasizing the potential of biopesticides as sustainable alternatives for pest management and crop protection. However, there is a necessity to consolidate existing information regarding the classification, mechanisms of action, and market dynamics of biopesticides, including microbial agents such as B. thuringiensis and Trichoderma spp., as well as their role in minimizing crop losses while ensuring the safety of non-target organisms and ecosystems.

Our work is focused on the evaluation of the feasibility of utilizing agro-industrial wastes as economical substrates in both solid-state and submerged fermentation processes for the production of biopesticides, with a focus on nutrient recovery, waste minimization, and adherence to circular economy principles. This permits us to investigate the principles of process intensification in the manufacturing of biopesticides, encompassing upstream processes such as strain optimization and high-density fermentation, downstream processes including purification and drying, as well as formulation stages, with an emphasis on improving productivity, energy efficiency, and scalability.

This contribution defines the primary benefits of process intensification strategies, including decreased production costs, enhanced product quality, reduced environmental impact, and expedited development timelines, within the framework of sustainable food production systems, but also to examine contemporary developments in biopesticide patents and worldwide market forecasts, highlighting advancements in formulations, regulatory structures, and business prospects that facilitate the shift towards residue-free, organic agricultural methods.

This review aims to critically assess the function of biopesticides in enhancing food safety, quality, and sustainability, emphasizing the integration of process intensification strategies to improve production efficiency and minimize environmental impact. We conducted comprehensive research aimed at improving the safety, quality, and sustainability of food products through the production of biopesticides within the framework of process intensification. In order to fulfill the aforementioned objectives, a thorough array of keywords was employed across multiple search engines, such as Google Scholar, PubMed, Web of Science, ScienceDirect, and Scopus. The keywords identified include essential concepts such as biopesticides, process intensification, agro-industrial waste, solid-state fermentation, submerged fermentation, B. thuringiensis, Trichoderma spp., sustainable agriculture, food safety, food quality, food sustainability, biological control agents, microbial biopesticides, biofungicides, bioinsecticides, bioherbicides, synthetic pesticides, pesticide resistance, circular economy, fermentation substrates, biopesticide production, biopesticide market, patents related to biopesticides, environmental impact of pesticides, crop protection, and pest management.

This review focused on studies published between 2015 and 2025, highlighting recent research to incorporate the latest scientific advancements while also taking into account foundational studies from previous years. The article offers a thorough review of current research on biopesticide production within the context of process intensification with the goal of enhancing food safety, quality, and sustainability. In this study, we use process intensification to look at how making biopesticides affects food product safety, quality, and sustainability. An extensive review of the existing literature, coupled with recent advancements in technology, ensures that the results are reliable and advantageous for professionals in research, science, and industry. This will assist individuals engaged in the exploration of novel opportunities for enhanced operations in a sustainable manner, focusing on various aspects. Furthermore, individuals engaged in the same field will discover new opportunities.

2. Synthetic Pesticides

Agriculture emerged during the Neolithic era as societies transitioned from hunting and gathering. The initial crops cultivated included wheat and barley. However, alongside this advancement, the emergence of pests posed significant risks to crop yields. Mammals, insects, mollusks, fish, birds, nematodes, and microorganisms, along with certain plant species, can hinder the complete and secure development of crops [19]. These pests infiltrate, inflict damage, and compromise crop health in their quest for sustenance. The earliest recorded information regarding the application of methods to address this issue in ancient Mesopotamia indicates the utilization of sulfur. In the 19th century, significant quantities of lead (Pb), arsenic (Ar), and copper (Cu) were employed for the management of weeds and pests [20,21].

Historically, these methods or agents were referred to as biocides, a term denoting life elimination. However, the terminology has shifted to pesticides, as it more accurately reflects the fact that these products target only pest organisms while sparing non-harmful species [22]. A pesticide refers to any substance or compound utilized to combat, eliminate, or deter pests, which may include microbial, animal, or plant organisms. These substances can be applied throughout various stages of raw material processing, including cultivation, production, transportation, storage, and distribution, as well as during the diverse transformation processes in multiple industries. The agricultural sector is particularly impacted by pests and pathogens, leading to significant economic losses [23,24].

Pesticides can be categorized into various types based on their specific actions, including acaricides, fungicides, bactericides, herbicides, and insecticides, among others [11,13,14,24]. Additionally, they can be classified according to their intended application, such as for phytosanitary purposes, animal use, industrial use, or storage. Similarly, various groups can be classified based on their chemical composition, which may originate from compounds such as urea, coumarins, triazines, arsenicals, carbonates, organochlorines, and phosphorus, among others. Additionally, these substances can be categorized by their form or application, with the primary types including liquids, solids, powders, gases or liquefied gases, and aerosols [25,26].

The utilization of these resources contributes to cost savings in global agriculture by mitigating losses attributed to insects and pests [27,28]. During the 1980s, an agricultural revolution emerged, characterized by the widespread application of pesticides, as society identified them as a swift, effective, and relatively low-cost solution for enhancing crop yields [29,30]. This practice became prevalent in the sector, leading to significant economic advancements, as various studies have indicated that the integration of these techniques into agricultural practices resulted in profitability increases of up to 50% [20,31].

The problem with these methods is that pesticides are not poisons as such, but they can have harmful side effects that make them poisonous to people and other animals [32]. In addition, it has been proven that these substances can be ineffectual if used irrationally and without discrimination, which presents serious difficulties to environmental safety. The development of resistance by pests makes their management more challenging, if not impossible. When considering the rise of new agricultural pests and the prevalence of important disease vectors like malaria mosquitoes, this issue becomes even more worrisome [33,34]. Research and data about the negative impacts and consequences linked to these activities abound. Because of this, the European Union and other countries have set deadlines for manufacturers in this industry and legislated that harmful compounds be reduced in agricultural soils. There is concern that outlawing these chemicals may cause major crop failures, which in turn will drive up the prices of food and raw materials, which might lead to a decline in employment and a worsening of world hunger [35,36].

3. Biopesticides

The primary aim of agriculture is to provide sustenance for the population. Consequently, efforts are being made to identify safe solutions, with biotechnological tools emerging as a viable answer that continues to be the subject of ongoing research [37,38,39]. While the application of biopesticides is not a novel concept, with historical evidence tracing back to ancient practices, the term “biopesticide” is a more recent designation [8,13,20,40]. Biopesticides can be characterized as pesticides derived from biological sources or as organisms themselves [9]. Biological agents or compounds derived from them include microorganisms such as fungi, bacteria, and viruses, as well as substances extracted from plants, utilized for pest management purposes [41,42].

Environmental contamination, resistance in target species, and chronic toxicity are some of the many negative outcomes that have resulted from the widespread use of pesticides in recent years in an effort to meet the increasing demand for food while simultaneously improving agricultural output and quality [43,44]. Therefore, the use of biopesticides is driven by the urge to create products or set protocols that minimize human and environmental consequences [8].

The biopesticide market on a global scale is part of the crop protection sector, at approximately USD 70.7 billion projected for 2025, and accounts for around 14% of this market, equal to USD 10.12 billion. This figure surpasses the previously established minimum threshold of 5% [8,13,45,46]. Biopesticides, originating from natural sources such as microorganisms and plants, are experiencing a significant compound annual growth rate (CAGR) of 10–16% per year. This growth is propelled by the increasing demand for sustainable and organic farming practices, regulatory prohibitions on synthetic pesticides, exemplified by the EU’s Green Deal, and advancements in technologies, including RNA-based products [13,45,47,48]. The United States has a significant number of over 390 registered biopesticide active ingredients, which exceeds the previously mentioned figure of 200. This is facilitated by efficient EPA approval processes and a growing demand for organic products [8,40,45,49,50]. The European Union currently has approximately 65 active substances, closely aligning with the reported figure of 60. This increase is driven by initiatives aimed at achieving 25% organic land by the year 2030; however, the process of approval is hindered by rigorous regulatory frameworks [45,51,52]. According to predictions, the biopesticide industry may reach record highs by 2032, which might lead to a shift in farming towards more environmentally friendly techniques. But problems with scalability and the requirement for better farmer education may prevent this change from happening [2,8,13,46].

Agricultural practices across the world are greatly affected by the use of biopesticides [4,5,8,53]. If used in a wider variety of agricultural regions, their effectiveness might be increased [12,54]. Because these biopesticides are organic, crops and soil are able to fully absorb them, which is a major plus [8,14,28,50,54]. Another benefit is that they do not leave harmful residues behind. Their use also reduces the likelihood of harm coming to creatures and species that are not their intended targets. There is no risk of insect resistance or soil contamination from residual chemicals left behind by biopesticides, unlike synthetic alternatives [8,9,11]. Additionally, it is feasible to achieve these goals at cheaper prices than commercial synthetic pesticides if we stick to traditional approaches [50,55,56].

Numerous investigations highlight the significant potential of biopesticides, particularly focusing on the efficacy of a biopesticide containing Penicillium frequentans in managing Monilinia spp. within nectarine cultivation [57]. These studies emphasize the importance of microbial variability in the resulting fruit, indicating that P. frequentans facilitates pathogen control while preserving the integrity of the natural microbiome. This exemplifies a highly precise action within this category of emerging pest controllers, which demonstrate multiple benefits while minimizing collateral damage.

When thinking about sustainable crop production in the future, biopesticides provide a lot of benefits [4,7,8,36,37,38]. Biodegradable tools with self-perpetuation potential, using living organisms and natural products for pest management, offer substantial advantages [4,7,9,43,50,53]. Improved pest infestation targeting, lower toxicity, and protection of non-target species are all benefits of this technique, which also has a shorter shelf life. There are a few downsides to these compounds, though, especially when it comes to how well they work against rapidly spreading pests [36]. When comparing them to synthetic alternatives, this constraint is a major problem for producers and field workers. Furthermore, unlike broad-spectrum pesticides that may kill any microbes and pests regardless of their useful or harmful nature, biopesticides need accurate identification of the target pathogen and sometimes include multiple biopesticides [8,9,36]. Existing variables in crops and soils, affected by different causes, are another topic to think about. Such systems are susceptible to change and may not always operate at their best because they are living things. An analysis of the environmental factors influencing the control mechanisms may provide light on how to manage or reduce this problem [11,58].

The existing regulatory framework lacks definitive parameters for the assessment of these substances, failing to acknowledge their significance [50,59,60,61]. Progress remains insufficient, as these substances are not evaluated alongside their primary counterparts, commercial synthetic pesticides, regarding production, efficacy, and cost [13,40,50,59]. This has led to malpractice among manufacturers, who unjustly compare them to chemical products, resulting in their degradation in both agricultural fields and market viability [15,59,60]. Consequently, establishing a global regulation that defines critical criteria for the production, functionality, efficacy, and cost-effectiveness of biofungicides is essential [50,53,59,61]. This will provide greater assurance to producers who are investing in these innovative green technologies that contribute positively to the environment [59,61].

4. Agro-Industrial Waste for Biofungicide Production

One of the essential requirements for human beings is food security, a domain that is continually expanding, with growth strategies aimed at enhancing its processes [27,36,62]. The food industry, in its efforts to meet increasing demands, experiences significant losses of organic material, referred to as waste [39,63]. This waste is generated at various stages of food processing, including harvesting, post-harvest handling, storage, transportation, retail, and domestic disposal [39,64,65]. Food waste is estimated to constitute approximately 30 to 40% of the overall supply [39,63]. The materials originating from food processing, often classified as “waste,” possess a complex nutrient profile that can be utilized to maximize the potential of all components or fractions, leading to the extraction of a diverse array of compounds [39,63,64,66]. In recent years, the concept of circular economy has been introduced to reduce waste produced in diverse industrial processes [17,39,65]. The aim of the circular economy is to optimize resource utilization while reducing the waste produced during a process. In light of the significant volume of waste produced by the food industry, innovative strategies are being explored to facilitate comprehensive utilization [6,17,39,65]. These materials have been utilized as fermentation substrates for the extraction of various metabolites [63,64,66]. Fermentation systems facilitate the transformation of substrates into bioproducts, enabling their application in the production of biopesticides [39,64,66,67,68]. Biopesticide production processes have utilized fermentation systems, including the submerged system and the solid-state system [39,65,66]. The final category of fermentation has gained significant relevance in this field due to its advantages over submerged fermentation. It enhances the yields of the target products, reduces production times, and requires lower investment in the conditioning of fermentation substrates, making its application more favorable [18,39,65,66].

For the production of biopesticides, agro-industrial wastes are commonly used as fermentation substrates. Various materials have been reported for this purpose, with an emphasis on those that are nutrient-rich. Some residuals have also been combined with other types of residuals to create culture medium that can support the growth of microbes that are poisonous to many different types of diseases [39,41,42,65,66,69]. As a biopesticide made from agricultural and industrial waste, spores of the Bacillus genus, particularly of the thuringiensis species, are among the most widely used [70,71,72]. Because of its capacity to produce endotoxins, which are crystal proteins that attack insects of the Cole-optera, Lepidoptera, and Diptera orders, this microbe is widely used in biopesticide production [22,73]. It also works well against terrestrial gastropods and phytopathogenic nematodes. Nearly all commercially marketed biopesticides are derived from B. thuringiensis [2]. This bacteria is effective because it can make a delta (δ)-endotoxin, which binds to receptors on epithelial cells and kills the larvae [74,75]. This bacteria also has the ability to create spores, which may then multiply on insects. This makes it easier for the spores to invade and increases the biopesticides’ deadly potential [76,77,78]. This endotoxin is linked to sporulation and has a protein and carbohydrate composition (95% protein and 5% carbohydrates) [18]. B. thuringiensis biopesticides grown on agricultural and industrial waste are more toxic than their synthetic counterparts, according to the research [23,79,80]. According to studies conducted on B. thuringiensis, spore production is greatly affected by variables such as temperature, biodegradability, and oxygen levels.

Various microorganisms, including Beauveria and Trichoderma, are utilized in the formulation of biopesticides (

Table 1. Production of biofungicides from agro-industrial waste.

Microorganism	Agro-Industrial Waste/Substrate	Fermentation Type	Key Outcomes/Notes	References
B. mojavenis A21	Agro-industrial bio-waste	Submerged fermentation	Lipopeptide biosurfactants with biocontrol efficiency	[78]
B. thuringiensis	Starch industry wastewater	Submerged fermentation	High spore yield; cost reduction; enhanced lethality vs. synthetic media	[2,18]
B. thuringiensis	Shrimp pond sludge	Submerged fermentation	Effective against Bactrocera dorsalis	[80]
B. thuringiensis	Cassava peels (via pilot-scale bioreactor)	Solid-state fermentation	Mass production of Trichoderma-like activity; process intensification	[82]
B. thuringiensis + biowaste digestate	Two-stage aeration strategy	Solid-state fermentation	Improved biopesticide yield and stability	[86]
B. thuringiensis subsp. aizawai	Agricultural raw materials and agro-industrial wastes	Submerged fermentation	Efficient, cost-effective spore and δ-endotoxin production	[81]
Bacillus spp.	Almond hulls	Solid-state fermentation (biosolarization)	Production of organic acids (lactic, acetic, formic, succinic); nematicidal activity	[67]
Beauveria bassiana	Rice husk	Solid-state fermentation	High conidial yield; biopesticide formulation	[17]
Metarhizium koreanum	Optimized solid waste (nutritional supplementation)	Solid-state fermentation	Enhanced conidia and cuticle-degrading enzyme production	[89,94]
T. asperellum	Various organic solid wastes	Solid-state fermentation	6-pentyl-α-pyrone, conidia, lytic enzymes	[83]
T. harzianum	Rice husk	Solid-state fermentation	Antagonistic metabolites; high spore density	[17]

). These fungi are acknowledged for their antagonistic properties against a diverse range of pathogen species [6,81,82,83]. The pathogenicity of these fungi is attributed to their ability to invade hosts, and the resultant products include spores and fermentation extracts that contain a diverse array of toxic metabolites effective against numerous pathogens [84,85]. Additional studies have concentrated on the utilization of biowaste or its digestates, in which enzymes, biosurfactants, and biopesticides have been generated [80,86]. A diverse range of residues has been utilized as fermentation substrates, including almond hulls, where research indicates that the fermentation process facilitates the production of organic acids such as lactic, acetic, formic, and succinic acids [67]. The toxic effects of these organic acids on nematodes have been substantiated through research. Research indicates that lipopeptides synthesized by the genus Bacillus serve as a highly effective alternative for managing fungal infections that impact various crops [78,86]. The investigation conducted in this domain centers on assessing the appropriateness of utilizing agro-industrial by-products as fermentation substrates for the production of biopesticides [17]. Additionally, it encompasses the analysis of fermentation parameters, including temperature, inoculum concentration, humidity, mass–volume ratio, and oxygenation, among others [12,87,88,89,90,91,92,93].

5. Process Intensification

The implementation of process intensification in biopesticide production is essential for enhancing, optimizing, and broadening the market for these bioproducts [87,88,89]. This advancement is critical for facilitating the transition away from conventional chemicals that pose significant risks to health and the environment while also maintaining crop quality [39,90,91]. Furthermore, it plays a vital role in the establishment of sustainable food production systems, which are integral to the large-scale circular economy [39,88,92].

Process intensification offers a great chance to develop more efficient, environmentally friendly, cost-effective, and sustainable microbial bioprocesses, as mentioned before [88,93]. This approach uses techniques that aim to drastically cut down on energy consumption, waste, and equipment size, all the while working towards the goal of producing biopesticides sustainably for modern agriculture, with a focus on protecting non-harmful plants and animals and preserving the environment for future generations [8,87,88,93]. Figure 1 illustrates the benefits of implementing the process intensification concept in the production of biopesticides. The concept of process intensification in biopesticide production offers several advantages [8,87,88,93,94], including (1) increased productivity, (2) reduced production costs, (3) improved downstream processing, (4) enhanced product quality, (5) environmental benefits, and (6) shorter development times.

The concept of process intensification reveals several advantages of biocontrol agents compared to chemical pesticides while also highlighting various agro-industrial wastes and the innovative technologies employed to produce these products [39,87]. The objective is to outline the challenges and perspectives that need to be addressed for the biopesticide market to sustain its growth trajectory [87,92]. From this perspective, it is essential to effectively coordinate various processes, unit operations, or procedures and to foster synergistic effects throughout the development of bioprocesses [87,97], integrating and linking all relevant processes to achieve optimal performance and minimal energy usage [97]. The production of biopesticides through process intensification offers the potential to develop innovative, efficient, cost-effective, and streamlined bioreactors. This approach enhances volumetric productivity and selectivity while promoting reduced energy consumption, all without compromising product quality and safety [87,97]. The production phase should be integrated with the separation phase to achieve optimal outcomes while minimizing pollution generation. Both stages may be enhanced by incorporating a procedure for the recovery of solvents and materials that are amenable to reprocessing [97]. Figure 2 shows the main potential and challenges related to biopesticide production.

6. Advantages of Process Intensification in Biopesticides Production

Process intensification serves as a transformative methodology focused on improving the efficiency, compactness, and sustainability of operations within the chemical, biochemical, and biotechnological fields [88,100]. In the realm of biopesticide production, process intensification presents considerable benefits, given that this approach generally encompasses several stages, including microbial fermentation, extraction of bioactive compounds, purification, and formulation [88,89]. The application of process intensification strategies in the manufacturing of biopesticides has the potential to significantly enhance process productivity and yield while also decreasing production costs and energy usage [88,89,100]. Furthermore, process intensification enables improved regulation of process parameters, reduces waste production, and increases the selectivity and purity of the end product [88,100]. The collective advancements enhance the efficiency of downstream processing and elevate the quality of the final product [88].

Table 2. Primary advantages of process intensification strategies in biopesticide production.

Advantage	Description	Mechanism/Examples	Quantitative Impact	References
Increased productivity	Higher biomass and metabolite yield per unit volume and time	High-cell-density bioreactors, continuous cultivation, AI-driven process control	>50% increase in volumetric productivity (e.g., B. thuringiensis spore yield in starch wastewater)	[2,88,97]
Reduced production costs	Lower substrate, energy, and capital expenditure	Valorization of agro-industrial waste (rice husk, starch wastewater), compact modular reactors	35–59% reduction in production costs	[16,18,39]
Enhanced downstream processing	Improved recovery, purity, and processing speed	Membrane bioreactors, hybrid separation, in situ product extraction	Up to 70% reduction in downstream processing time; >90% recovery efficiency	[88,93,96]
Improved Product Quality and Stability	Higher purity, bioactivity, and shelf life	Nano/microencapsulation, spray-drying with stabilizers, real-time quality monitoring	Shelf life extended from 6 to >18 months; >95% spore viability after 12 months	[89,93,101]
Environmental benefits	Reduced ecological footprint and waste	Energy-efficient systems, zero-liquid discharge, full substrate valorization	40–60% lower CO2 emissions; supports circular economy models	[39,87,92]
Shorter Development and Scale-up Time	Accelerated research and development and their commercialization	Digital twins, predictive modeling, modular intensified bioreactors	30–50% reduction in process development and scale-up timeline	[88,97,100]

presents a summary of the key benefits linked to the design and implementation of process intensification strategies in the production of biopesticides.

7. Patents and the Biopesticide Market

The biopesticide industry has experienced a significant rise in patent activity, indicating continuous advancements in formulation technologies, microbial strains, and application techniques aimed at improving efficacy, stability, and environmental compatibility [8,13,101]. From 1982 to 2021, there were 2371 patent documents filed worldwide concerning biocontrol agent formulations [101]. The United States was at the forefront of this, with 694 patents, while China and Europe also made notable contributions. In 2015, patent filings reached their highest point, totaling 278 documents [101]. These filings were mainly categorized under biocides, pest repellents, attractants, or plant growth regulators that originate from microorganisms, viruses, or fungi [101]. Recent trends demonstrate ongoing expansion; for example, U.S. universities and research institutions submitted 185 patents related to biopesticides from 2020 to 2023 [102]. The European Patent Office (EPO) has issued approximately 5982 patents related to biopesticides, whereas the United States Patent and Trademark Office (USPTO) has granted around 2256 patents, highlighting a concentration on fungicides, arthropodicides, and nematocides [13]. The patent landscape indicates a transition towards sustainable alternatives, showcasing a growing focus on biofungicides that integrate nanotechnology and botanical extracts, especially in areas characterized by strict regulatory standards [13,101].

Regulations limiting the use of synthetic pesticides, rising consumer demand for products with no trace of residue, and developments in process intensification that allow for scalable production are all factors driving the biopesticide market’s recent expansion [103]. Keeping CAGRs of 12–16% for biopesticides, as opposed to 3–5% for synthetic equivalents, is predicted to bring the biopesticide market to a scale similar to that of synthetic pesticides by the late 2040s or early 2050s, according to forecasts [103]. An estimated USD 244–283 billion would change hands in the worldwide biopesticide industry by 2025, making up around 3–4% of the total pesticide market [103,104]. Forecasts show that by the years 2029–2032, the market value will have increased to between USD 15 billion and USD 28 billion [103].

Prominent entities in the biopesticides sector comprise BASF SE (Ludwigshafen, Germany), Syngenta AG (Basel, Switzerland), Bayer AG (Westphalia, Germany), Koppert Biological Systems (Berkel en Rodenrijs, The Netherlands), Certis Biologicals (Columbia, SC, USA), Marrone Bio Innovations (Davis, CA, USA), Corteva Agriscience (Indianapolis, IN, USA), FMC Corporation (Philadelphia, PA, USA), Andermatt Group AG (Grossdietwil, Switzerland), and Sumitomo Chemical Co., Ltd. (Tokyo, Japan) [103]. These organizations collectively contribute to advancements in microbial, biochemical, and plant-incorporated protectants. In North America, which includes the United States, Canada, and Mexico, biopesticide sales represent roughly 36–40% of the global market [103]. This is supported by favorable policies such as the U.S. EPA’s accelerated registration process for reduced-risk pesticides and the extensive use of these products in organic agriculture [102]. Recent market entries feature innovative formulations that have received approval in areas including North America, Europe, Africa, and Australia. Companies such as Andermatt Biocontrol, Certis USA, and Koppert are set to launch products aimed at lepidopteran pests and soil-borne pathogens, with some introductions anticipated as late as 2025 [105,106].

Approximately 74% to 90% of the world’s microbial biopesticides are generated from B. thuringiensis (Bt) [107]. This makes Bt-derived products an essential part of the bioinsecticide industry. More than 35 million hectares of genetically modified crops in North America use Bt formulations, and the company has a 40% market share in the bioinsecticide industry overall [107,108]. In contrast, their market share is limited to about 8–10% in the European Union due to regulatory hurdles, specifically the more rigorous licensing processes for microbial agents [109]. More than 2000 biopesticide products have been registered in China as of 2024, with a significant portion coming from Bt formulations [13,110]. The significance of botanical and microbial active ingredients in promoting sustainable agriculture has been underscored by the recent approval of five more biopesticides in 2025 [111]. Improvements in food safety, quality, and sustainability have been made possible by recent developments in process intensification tactics, such as enhanced fermentation and encapsulation processes, which seek to increase the field efficacy and shelf life of biopesticides [101,103].

8. Looking Ahead: The Possible Future and Research Possibilities

More than ten billion people will be living on the globe by the turn of the century; thus, sustainable agricultural methods that put an emphasis on producing safe, high-quality food are critically important [1]. A vital substitute for synthetic pesticides—linked to toxicity, resistance development, and environmental damage—are biopesticides, which are produced by process intensification techniques [4,33]. They reduce production costs, increase yields, and minimize waste by using agro-industrial wastes as economical substrates in sophisticated fermentation systems like SSF or high-cell-density bioreactors [16,88]. Based on the principles of the circular economy and international sustainability initiatives such as the EU Green Deal, this section outlines potential pathways and research objectives to further biopesticide use in process intensification. With the world’s population expected to rise by more than a billion by the turn of the next century, there is an urgent need for environmentally responsible farming practices that prioritize safe, high-quality food.

The biopesticide sector might be worth anywhere from USD 19.77 billion to USD 28.61 billion by 2032, according to market predictions. This expansion is expected to be driven by a CAGR of 10% to 16%, which is supported by regulatory restrictions on synthetic alternatives and a rising desire for organic goods that do not leave residues [13,46]. Biopesticides will have the ability to compete with synthetics in the 2040s and 2050s if the problems of scalability are resolved [103]. Methods like continuous culture with real-time monitoring, membrane separations, and formulation phases like nanoencapsulation for controlled release are all part of process intensification, which integrates these processes to achieve this goal. This method decreases energy usage and effluent production while increasing productivity, purity, and shelf life [87,93]. Compared to synthetic media, Bt-derived products—which make up 74% to 97% of microbial biopesticides—show better entomotoxic efficacy when grown on substrates such starch wastes or rice husks [2,18].

Future advancements depend on the synergistic integration of process intensification with new technologies. Genome editing techniques, such as CRISPR-Cas9, have the potential to create hyper-productive strains of Trichoderma spp. or Beauveria bassiana, which would exhibit expanded antagonistic capabilities against phytopathogens including Fusarium and Rhizoctonia. Concurrently, AI-driven bioreactors can enhance operational parameters (temperature, pH, oxygenation) to achieve volumetric productivity improvements surpassing 50% [83,97]. Formulations utilizing nanotechnology, including lipopeptide-loaded nanoparticles derived from Bacillus spp., offer the potential for improved bioavailability and targeted delivery, addressing issues of specificity and the rapid proliferation of pests [78,89]. Hybrid process intensification systems that integrate solid-state fermentation with submerged fermentation in modular, compact reactors have the potential to valorize a variety of waste materials, such as almond hulls, which can produce nematocidal organic acids. This approach supports the development of zero-waste biorefineries [39,67].

There are still research gaps that necessitate thorough examination. Longitudinal field trials are crucial for quantifying the efficacy of biopesticides derived from process intensification across various agroecologies. These trials will assess the preservation of microbiomes and the impacts on non-target organisms in comparison to broad-spectrum synthetic alternatives [57]. Secondly, standardized regulatory frameworks should assess process intensification products alongside chemicals, integrating life-cycle assessments to evaluate cost-effectiveness and biodegradability [50,59]. Third, techno-economic models must investigate the variability of waste streams, the scaling of inoculum, and the integration of downstream processes to attain sub-synthetic pricing [50]. Ultimately, collaborative approaches that integrate metagenomics for the development of innovative biocontrol agents with digital twin technology for process simulation have the potential to expedite commercialization, aiming for 25% organic land coverage by the year 2030 [52].

In a nutshell the production of biopesticides from agro-wastes through process intensification represents a significant advancement in agricultural practices, enhancing food security while maintaining safety and sustainability standards. Focused investigations into strain engineering, advancements in formulation, and alignment of regulatory frameworks will drive this transformation, guaranteeing robust crops in the face of climatic variability.

This contribution intentionally encompasses a broad range of topics. This integrative scope is not incidental, but rather essential to address the multifaceted nature of biopesticide development and deployment within modern food systems.

Unlike conventional reviews that focus narrowly on the biological efficacy of biopesticides, specific microbial strains, or isolated formulation strategies, this manuscript adopts a systems-level perspective. The production and application of biopesticides inherently involve interconnected domains, including microbial biotechnology, bioprocess engineering, formulation science, regulatory considerations, environmental sustainability, and food safety. Treating these elements in isolation risks overlooking critical interdependencies that ultimately determine the feasibility, scalability, and real-world impact of biopesticides in agri-food chains.

The incorporation of the process intensification (PI) concept serves as a unifying framework that justifies and necessitates this multidisciplinary coverage. PI is not limited to reactor design or operational optimization; rather, it promotes the holistic redesign of production systems to achieve higher efficiency, reduced resource consumption, minimized waste generation, and improved product consistency. When applied to biopesticide production, PI naturally bridges upstream microbial selection and genetic optimization, intensified fermentation strategies, downstream processing, formulation stability, and integration into sustainable food production systems. As a result, addressing these topics collectively is fundamental to demonstrating how PI can transform biopesticide production from a laboratory-scale concept into an industrially viable and sustainable solution.

This broad thematic coverage constitutes a key novelty of the review. The existing literature typically addresses biopesticides from fragmented viewpoints—biological activity, environmental benefits, or regulatory challenges—without explicitly linking these aspects to intensified production strategies and their downstream implications for food safety and quality. By contrast, this review synthesizes these traditionally separated areas, highlighting how intensified bioprocesses can simultaneously enhance microbial efficacy, reduce contamination risks, improve formulation robustness, and lower environmental footprints.

Furthermore, the review positions biopesticides not merely as crop protection agents, but as strategic enablers of safer and more sustainable food systems. By explicitly connecting production technologies with food quality, safety assurance, and sustainability metrics, the manuscript advances beyond descriptive summaries of existing technologies and provides a conceptual roadmap for future research and industrial implementation.

In this sense, the breadth of topics covered should be viewed as a strength rather than a limitation. It reflects the emerging paradigm in agri-food biotechnology, where innovation arises from the convergence of biological, engineering, and sustainability principles. The novelty of the manuscript lies precisely in this convergence, offering a comprehensive and forward-looking perspective that is currently underrepresented in the biopesticide literature.

9. Concluding Remarks

With the global population projected to exceed 10 billion by the end of this century, environmentally and health-conscious farming practices that ensure food security are more critical than ever. This review examines biopesticides as sustainable alternatives to synthetic pesticides, emphasizing process intensification as a means to improve production efficiency, scalability, and cost-effectiveness while mitigating toxicity, resistance development, and ecological contamination. The review integrates analyses of patent trends, market projections, limitations of synthetic pesticides, the use of agro-industrial wastes as substrates, and intensification strategies across upstream, downstream, and formulation stages. Biopesticide classifications, mechanisms of action, and market dynamics are also consolidated.

The findings highlight that biopesticides derived from biochemical or microbial sources—particularly Bacillus thuringiensis (≈97% of the market) and Trichoderma spp.—effectively control pests through targeted mechanisms such as antibiosis and hyperparasitism, reducing non-target effects and resistance risks. The use of agro-industrial byproducts in solid-state and submerged fermentation aligns with circular economy principles, reducing production costs by 35–59% while valorizing waste streams. Advances in process intensification, including nanoencapsulation, AI-driven monitoring, continuous cultivation, and intensified bioreactors, have significantly enhanced productivity, stability, and environmental performance, enabling residue-free food production.

Market analyses indicate rapid growth, with the biopesticide sector projected to reach USD 8–10 billion by 2025 and grow at a CAGR of 12–16%, potentially approaching synthetic pesticides by the 2040s–2050s, driven by regulatory shifts such as the EU Green Deal and rising demand for organic products. Despite sustained innovation—evidenced by 2371 patent filings between 1982 and 2021—challenges remain in regulatory harmonization, field efficacy, and scalability, underscoring the need for further strain engineering, long-term field trials, and techno-economic modeling. Overall, biopesticides enhanced through process intensification represent a transformative pathway toward safer, higher-quality, and more sustainable food systems.