1 Introduction

Bacillus thuringiensis (Bt) biopesticides have emerged as a pivotal tool in sustainable agriculture, offering an environmentally friendly alternative to chemical pesticides. Despite their benefits, Bt biopesticides face significant regulatory and market challenges that hinder their widespread adoption. Bt is a soil bacterium known for its insecticidal properties, primarily due to the production of Cry and Cyt proteins, which are toxic to specific insect pests (Sanahuja et al., 2011). These proteins have been utilized in various formulations, including sprays and transgenic crops, to protect against insect damage. The use of Bt biopesticides has been shown to reduce the reliance on chemical pesticides, thereby minimizing environmental contamination and health risks (Egbuna et al., 2020). Additionally, Bt has applications beyond pest control, such as promoting plant growth and serving as a biofertilizer (Kumar et al., 2021).

The regulatory landscape for Bt biopesticides is complex and varies significantly across different regions. Regulatory bodies must ensure the safety and efficacy of these biopesticides while addressing public concerns about genetically modified organisms (GMOs) and potential resistance development in target pests (Ballardo et al., 2020). Market challenges include the high costs associated with the development and registration of new Bt strains, competition with chemical pesticides, and the need for public acceptance and awareness (Liang et al., 2018; Rodríguez, 2019). These challenges can impede the commercialization and adoption of Bt biopesticides, despite their proven benefits.

This study analyzes the regulatory frameworks for Bt biopesticides in different regions, identifies market challenges, and proposes strategies to overcome these challenges, highlighting the potential of Bt biopesticides in promoting sustainable agriculture and reducing environmental impact. By addressing these objectives, this study aims to foster a broader understanding of Bt biopesticides and support their integration into sustainable agricultural practices.

2 Overview of Bt Biopesticides

2.1 Mechanism of action

Bacillus thuringiensis (Bt) is a soil bacterium that produces insecticidal toxins, which are highly specific to certain insect pests. The primary mode of action involves the ingestion of Bt spores and crystalline toxins by the target insect larvae. Once ingested, the alkaline environment of the insect gut activates the toxins, which then bind to specific receptors in the gut lining, causing cell lysis and ultimately leading to the death of the insect (Kumar et al., 2019). This specificity makes Bt a favorable alternative to broad-spectrum chemical pesticides, as it targets only the pest species without harming non-target organisms.

2.2 Types and applications

Bt biopesticides are available in various formulations, including spores and crystals, which are used in agriculture, forestry, and mosquito control. There are different subspecies of Bt, each targeting specific pests. For instance, Bt subsp. kurstaki is effective against lepidopteran pests such as bollworms and loopers, while Bt subsp. israelensis and Bt subsp. sphaericus are used for mosquito control (Kumar et al., 2019). Recent advancements have also explored the combination of Bt with nanotechnology to enhance its efficacy, reduce dosage rates, and improve field persistence (Devi et al., 2019). Additionally, Bt-based biopesticides are being developed to address challenges posed by climate change, such as higher temperatures and extended shelf-life during storage.

2.3 Benefits and limitations

Bt biopesticides offer several benefits over conventional chemical pesticides. They are less toxic to humans and non-target organisms, decompose faster, and are effective in smaller quantities (Ndolo et al., 2019). These attributes make Bt an integral component of Integrated Pest Management (IPM) programs, which aim to reduce the reliance on synthetic chemical pesticides. However, the adoption of Bt biopesticides faces certain limitations. Production and formulation costs can be high, and there are challenges related to the efficacy of downstream processing and formulation development (Rad et al., 2016). Additionally, despite the environmental and health benefits, the market growth of Bt biopesticides has been slower than expected, partly due to regulatory hurdles and farmers' reluctance to switch from synthetic pesticides (Sansinenea, 2016; Zhang et al., 2017).

Bt biopesticides represent a promising and eco-friendly alternative to chemical pesticides, with specific mechanisms of action, diverse applications, and significant benefits. However, addressing the limitations related to production costs, regulatory challenges, and market acceptance is crucial for their broader adoption and success in sustainable pest management.

3 Regulatory Frameworks

3.1 International regulatory bodies

The regulation of biopesticides is influenced by several international bodies that aim to harmonize and streamline the regulatory processes across different countries. Key organizations include the International Organization for Biological Control (IOBC), the European and Mediterranean Plant Protection Organization (EPPO), and the Organization for Economic Co-operation and Development (OECD). These bodies have made significant efforts to provide flexibility in biopesticide regulation, although challenges remain in achieving a uniform regulatory model that simplifies the registration process globally. The OECD, in particular, has been instrumental in developing guidelines and frameworks that member countries can adopt to ensure the safe and effective use of biopesticides (Arora et al., 2016; Desai et al., 2016).

3.2 National regulatory policies

National regulatory policies for biopesticides vary significantly across countries, reflecting different levels of stringency and procedural complexity. For instance, the European Union (EU) has a more complex and lengthy registration process compared to the United States (US). The EU's regulatory framework, governed by Regulation (EC) No. 1107/2009, imposes stringent requirements that often result in longer approval times and higher costs for biopesticide developers (Frederiks and Wesseler, 2018). In contrast, the US regulatory system, managed by the Environmental Protection Agency (EPA), is considered more supportive and efficient, facilitating quicker market access for biopesticides. India, another major player in the biopesticide market, has its regulatory framework overseen by the Central Insecticides Board and Registration Committee (CIBRC), which has registered numerous microbial formulations despite facing challenges related to quality control and large-scale production.

3.3 Comparative analysis of regulations

A comparative analysis of biopesticide regulations reveals significant disparities between regions, impacting the development and commercialization of these products. The EU's regulatory framework is often criticized for its complexity and the lengthy approval process, which can take approximately 1.6 years longer than in the US (Figure 1) (Frederiks and Wesseler, 2018). This complexity is attributed to the dual-level processes involving both EU and Member State (MS) regulations, leading to procedural bottlenecks at the national level.

Figure 1 Regulatory framework for MBCA registration in the EU (Adopted from Frederiks and Wesseler, 2018)

The regulatory framework for the registration of Microbial Biocontrol Agents (MBCA) in the EU is mainly divided into three stages: RMS stage, risk assessment stage and risk management stage, each stage has specific processes and requirements. The whole process is designed to ensure the safety and effectiveness of MBCA, and to safeguard public health and environmental safety through strict evaluation and management mechanisms. Through this comprehensive regulatory framework, the EU ensures that the application of MBCA in agriculture meets the highest standards, thereby promoting sustainable agricultural development.

In contrast, the US regulatory system is more streamlined, allowing for faster approval and market entry (Balog et al., 2017; Frederiks and Wesseler, 2018). Moreover, the regulatory environment in the EU has resulted in fewer biopesticide-active substances being registered compared to the US, India, Brazil, and China. This discrepancy is partly due to the EU's stringent regulatory criteria, which can deter manufacturers from pursuing biopesticide registration (Sansinenea, 2016). On the other hand, countries like India have made significant strides in biopesticide registration, with a growing number of microbial formulations being approved despite regulatory and quality control challenges (Kumar et al., 2019).

While international bodies like the IOBC, EPPO, and OECD strive to harmonize biopesticide regulations, national policies vary widely, affecting the global biopesticide market. The EU's stringent and complex regulatory framework contrasts with the more supportive and efficient systems in the US and other countries, highlighting the need for regulatory innovation and harmonization to promote the broader adoption of biopesticides.

4 Safety and Efficacy Assessments

4.1 Environmental impact studies

Environmental impact studies are crucial for understanding the potential effects of Bacillus thuringiensis (Bt) biopesticides on non-target organisms and ecosystems. Research has shown that Bt biopesticides are generally considered safe for the environment. For instance, Bt formulations have been found to have minimal adverse effects on non-target organisms such as Daphnia magna, although some studies have reported nonmonotonic dose-response relationships indicating potential vulnerabilities at certain concentrations (Machado et al., 2017). Additionally, the development of advanced formulations, such as microencapsulations and microgranules, has been aimed at enhancing the environmental stability and efficacy of Bt biopesticides under various environmental conditions, including exposure to ultraviolet radiation, rain, and temperature fluctuations.

4.2 Human health risk assessments

Human health risk assessments of Bt biopesticides have consistently demonstrated their safety. Bt is widely recognized as one of the safest microbial insecticides available, with no solid evidence linking it to human health issues such as diarrhea, despite concerns raised by regulatory bodies like the European Food Safety Authority (EFSA) (Raymond and Federici, 2017). Furthermore, the comprehensive framework for human health risk assessment of nanopesticides, which includes Bt-based formulations, suggests a tiered approach to evaluate potential risks. This framework tracks various entities, such as nanocarrier-active ingredient complexes and released active ingredients, to ensure thorough toxicity testing and safety evaluations (Kah et al., 2021). Overall, Bt biopesticides have a strong safety record, supported by extensive genotyping data that show no clinical infections associated with biopesticide genotypes.

4.3 Efficacy trials and field studies

Efficacy trials and field studies are essential for validating the performance of Bt biopesticides under real-world conditions. Advancements in downstream processing and formulation development, such as the use of membrane separation technology, have improved the potency and marketability of Bt biopesticides, ensuring longer shelf life and ease of application (Figure 2) (Rad et al., 2016).

Figure 2 Membrane separation technology (Adopted from Rad et al., 2016)

Membrane separation technology has many advantages, including higher productivity of purified spore crystal compounds, more compact purification equipment, easier scalability - consideration of downstream processing steps, safer, cleaner and more reliable purification process and lower overall cost. These advantages make membrane separation technology play a vital role in the production of Bt-based biopesticides, improve production efficiency, reduce costs, and improve the market competitiveness and use effect of products.

Bt formulations have been extensively tested and proven effective against a wide range of insect pests in agricultural and horticultural settings. The integration of nanotechnology into Bt formulations has further enhanced their efficacy, enabling better delivery, reduced dosage rates, and increased field persistence (Devi et al., 2019). These innovations have contributed to the growing acceptance and use of Bt biopesticides as a viable alternative to synthetic chemical pesticides (Ndolo et al., 2019).

5 Market Challenges

5.1 Market entry barriers

The market entry barriers for Bt biopesticides are significant and multifaceted. One of the primary challenges is the regulatory framework, which is often designed for chemical pesticides and imposes burdensome costs on the biopesticide industry. This regulatory environment creates substantial hurdles for the commercialization of biopesticides, as seen in both the European Union and India (Sansinenea, 2016; Keswani et al., 2019). Additionally, the complex selling channels and the perceived lack of efficacy compared to conventional pesticides further complicate market entry. Despite these barriers, there is a growing recognition of the need for sustainable pest management solutions, which could drive regulatory reforms and facilitate market entry for biopesticides.

5.2 Competition with conventional pesticides

Bt biopesticides face stiff competition from conventional chemical pesticides, which have been the mainstay of pest management for decades. The market for chemical pesticides, although declining, still dominates due to their established efficacy and widespread acceptance among farmers. The slow growth in the adoption of biopesticides can be attributed to farmers' risk aversion and their preference for tried-and-tested chemical solutions (Sansinenea, 2016). Moreover, the cost and perceived lower efficacy of biopesticides compared to chemical pesticides pose significant challenges. However, the increasing restrictions on chemical pesticides and the growing emphasis on integrated pest management (IPM) present opportunities for biopesticides to gain a larger market share (Chandler et al., 2011).

5.3 Consumer perceptions and acceptance

Consumer perceptions and acceptance play a crucial role in the market dynamics of Bt biopesticides. There is a general lack of awareness and education about the benefits and application of biopesticides, which hampers their adoption (Marrone, 2019). Additionally, lingering perceptions about the cost and efficacy of biopesticides compared to conventional pesticides further deter their acceptance. However, the growing consumer demand for sustainable and eco-friendly agricultural practices is gradually shifting perceptions in favor of biopesticides. Increased education and extension efforts, along with public and private sector policies, are essential to improve consumer acceptance and drive the adoption of biopesticides (Kumar et al., 2019; Baker et al., 2020).

6 Strategies to Overcome Regulatory Challenges

6.1 Streamlining approval processes

The regulatory approval process for biopesticides, including Bacillus thuringiensis (Bt) products, is often complex and time-consuming, which can hinder market entry and adoption. To streamline these processes, it is essential to develop regulatory frameworks that are specifically tailored to biopesticides rather than applying the same stringent requirements used for synthetic chemical pesticides. Simplifying the registration requirements, such as reducing the need for extensive toxicological and environmental tests, can significantly lower the barriers to market entry (Desai et al., 2016; Soetopo and Alouw, 2023). Additionally, harmonizing regulations across different countries can facilitate international trade and reduce the redundancy of approval processes.

6.2 Enhancing safety and efficacy data

To gain regulatory approval and market acceptance, it is crucial to provide robust data on the safety and efficacy of Bt biopesticides. This involves conducting comprehensive studies that demonstrate the low toxicity of Bt products to non-target organisms and the environment, as well as their effectiveness against target pests (Sansinenea, 2016). Advances in formulation technologies, such as microencapsulation and the use of nanotechnology, can enhance the stability and efficacy of Bt biopesticides, thereby providing stronger evidence to support regulatory submissions (Hernandez-Tenorio et al., 2022). Furthermore, ongoing research and development efforts should focus on generating high-quality data that meet the specific requirements of regulatory bodies.

6.3 Engaging with regulatory bodies

Proactive engagement with regulatory bodies is essential to address the challenges associated with the approval and commercialization of Bt biopesticides. This can be achieved by participating in regulatory consultations, workshops, and collaborative research initiatives that involve regulators, industry stakeholders, and academic researchers (Ndolo et al., 2019). Building strong relationships with regulatory authorities can help in understanding their concerns and requirements, thereby facilitating the development of more effective and compliant biopesticide products (Chandler et al., 2011; Desai et al., 2016). Additionally, advocating for the inclusion of biopesticides in Integrated Pest Management (IPM) programs and agricultural policies can promote their acceptance and use.

7 Strategies to Overcome Market Challenges

7.1 Marketing and education campaigns

One of the primary strategies to overcome market challenges for Bt biopesticides is the implementation of robust marketing and education campaigns. These campaigns should focus on educating farmers and other stakeholders about the benefits and proper usage of biopesticides. Educating farmers about the advantages of biopesticides, such as their eco-friendliness, target specificity, and biodegradability, is crucial for increasing their adoption (Sachdev and Singh, 2016). Additionally, promoting the success stories and case studies where biopesticides have been effectively used can help in building a positive perception among potential users (Ndolo et al., 2019).

7.2 Building consumer trust

Building consumer trust is essential for the widespread acceptance of Bt biopesticides. Trust can be fostered through transparent communication and involving farmers in the development and testing phases of biopesticide products. A case study on Bt maize in South Africa highlighted the importance of engaging farmers from the start of the project through field demonstrations and educational activities to build trust. Furthermore, ensuring that the biopesticides are effective and safe through rigorous testing and quality control can also help in gaining the confidence of the end-users (Sansinenea, 2016). Open communication and full disclosure between private sector companies and government regulatory bodies are also critical in building trust and facilitating regulatory processes.

7.3 Collaboration with agricultural stakeholders

Collaboration with various agricultural stakeholders, including government bodies, private sector companies, and research institutions, is vital for overcoming market challenges. Joint efforts can help in addressing regulatory barriers and promoting the use of biopesticides. For instance, the involvement of public-private partnerships (PPPs) in the development and commercialization of Bt biopesticides can lead to better regulatory compliance and market acceptance (Ezezika et al., 2012). Additionally, investment in domestic fermentation technologies and improved delivery systems through collaborative efforts can enhance the production and distribution of biopesticides. Supporting the development of public policies and private initiatives for the transition toward pesticide-free agri-food systems is also recommended to encourage the wide use of biopesticides (Soetopo and Alouw, 2023).

8 Case Studies

8.1 Successful regulatory approvals

The regulatory landscape for Bacillus thuringiensis (Bt) biopesticides has seen notable successes in various regions. For instance, in India, the Central Insecticides Board and Registration Committee (CIBRC) has registered over 30 products based on Bt subsp. kurstaki for use against lepidopterans, and additional products for mosquito control using Bt subsp. israelensis and Bt subsp. sphaericus (Kumar et al., 2019). This demonstrates a robust regulatory framework that supports the commercialization of Bt biopesticides. Furthermore, the global acceptance of Bt as a biopesticide is evident from its widespread use in agriculture, forestry, and mosquito control, highlighting its regulatory success across different sectors.

8.2 Market adoption examples

The market adoption of Bt biopesticides has been significant, particularly in regions with stringent regulations on synthetic pesticides. In India, Bt-based products have captured approximately 5% of the pesticide market, reflecting a growing preference for biopesticides amidst evolving consumer preferences and regulatory environments (Wafa et al., 2020). Additionally, the global biopesticide market is expanding annually, driven by the increasing demand for safer pest control options and the integration of biopesticides into Integrated Pest Management (IPM) programs. The adoption of Bt biopesticides is further supported by their effectiveness in small quantities and their rapid decomposition, which reduces environmental exposure and aligns with the global trend towards sustainable agriculture (Ndolo et al., 2019).

8.3 Lessons learned from failures

Despite the successes, there have been notable challenges and failures in the adoption and commercialization of Bt biopesticides. One significant issue is the slow growth in the use of biopesticides due to farmers' lack of confidence in selecting them over synthetic pesticides. This hesitation is often rooted in concerns about the efficacy and reliability of biopesticides. Additionally, the regulatory process for biopesticides can be cumbersome, with stringent quality control and production standards that can hinder large-scale production and market entry (Kumar et al., 2019). Another critical lesson is the need for comprehensive studies on the non-target effects of Bt biopesticides. For example, research has shown that Bt formulations can have nonmonotonic and potentially harmful effects on non-target organisms like Daphnia magna, challenging the assumption of their universal safety (Machado et al., 2017). These insights underscore the importance of addressing regulatory, production, and ecological challenges to enhance the adoption and effectiveness of Bt biopesticides.

9 Future Directions and Recommendations

9.1 Emerging trends in biopesticides

The biopesticide industry is witnessing significant advancements, driven by the need for sustainable agricultural practices and stringent regulations on synthetic pesticides. Recent developments include the exploration of new microbial species and innovative formulations. For instance, the use of entomopathogenic fungi and nematicidal fungi has shown promise in pest management. Additionally, the integration of nanotechnology with Bacillus thuringiensis (Bt) formulations is emerging as a promising trend, enhancing the efficacy and stability of biopesticides (Devi et al., 2019). The discovery of novel bacterial species such as Brevibacillus laterosporus and Chromobacterium subtsugae further expands the arsenal of biopesticides available for pest control (Ruiu et al., 2013).

9.2 Research and development priorities

To fully realize the potential of biopesticides, several research and development priorities must be addressed. First, there is a need for optimizing delivery systems and improving the formulation of biopesticides to enhance their effectiveness and shelf-life. Investment in domestic fermentation technologies and improved delivery systems is crucial for increasing the share of microbial biopesticides in the market (Kumar et al., 2019). Additionally, more field research is required to assess the effects of new biopesticide compounds under diverse cropping systems. Research should also focus on understanding the factors affecting growth, sporulation, and toxin formation in Bt to improve production yields (Wafa et al., 2020).

9.3 Policy and market recommendations

The regulatory landscape for biopesticides needs to be streamlined to facilitate their commercialization and widespread adoption. Current regulations often mirror those for synthetic pesticides, which can be a barrier to the market entry of biopesticides (Damalas and Koutroubas, 2018). Policies should be revised to reduce the requirements for toxicological, environmental, and residual tests specific to biopesticides. Governments should also support public policies and private initiatives aimed at transitioning towards pesticide-free agri-food systems (Soetopo and Alouw, 2023). Furthermore, educating farmers and stakeholders about the benefits and application of biopesticides is essential for overcoming market constraints and enhancing adoption rates (Sachdev and Singh, 2016).

10 Concluding Remarks

The research on Bt biopesticides has highlighted several critical points. Firstly, biopesticides, including those based on Bacillus thuringiensis (Bt), are recognized for their potential in sustainable agriculture due to their lower toxicity and environmental impact compared to synthetic chemical pesticides. Despite their benefits, the adoption of biopesticides remains limited, constituting only 1%~5% of the global pesticide market. Regulatory challenges are a significant barrier, as current regulations are often designed for chemical pesticides, imposing high costs and complex requirements on biopesticide producers. Additionally, there are technical challenges related to the production, formulation, and efficacy of Bt biopesticides, which need to be addressed to enhance their market presence.

Continued innovation in the field of Bt biopesticides is crucial for several reasons. Firstly, the development of new formulations, such as nano-Bt, can improve the efficacy, delivery, and field persistence of Bt biopesticides, making them more competitive with chemical pesticides. Secondly, advancements in fermentation technologies and the use of alternative substrates can reduce production costs, making Bt biopesticides more economically viable. Furthermore, regulatory innovation is needed to create a more favorable environment for biopesticide development and commercialization, which can be achieved through collaborative efforts between scientists, policymakers, and industry stakeholders. Lastly, integrating biopesticides into Integrated Pest Management (IPM) programs can enhance pest control strategies and reduce reliance on synthetic pesticides.

To address the regulatory and market challenges of Bt biopesticides, the following recommendations are proposed. Simplify and harmonize biopesticide regulations globally to reduce the burden on producers and facilitate market entry. Invest in research to develop new Bt formulations, such as nano-Bt, and improve existing production and formulation processes to enhance efficacy and reduce costs. Encourage public policies and private sector initiatives that support the transition towards sustainable agriculture and the use of biopesticides. Provide education and training to farmers on the benefits and use of Bt biopesticides to increase their confidence and adoption rates. Promote the integration of Bt biopesticides into IPM programs to achieve more sustainable and effective pest control. By addressing these recommendations, the potential of Bt biopesticides can be fully realized, contributing to sustainable agricultural practices and reducing the environmental impact of pest management.

Acknowledgments

The publisher would like to thank Dr. Fang X. from the Hainan Institute of Tropical Agricultural Resources for reviewing and providing valuable feedback on the manuscript. Special thanks are also extended to the two anonymous peer reviewers for their review and valuable suggestions for improvements.

Conflict of Interest Disclosure

The author affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

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