Biochemical pesticides: The frontier development in China's industry and Beyond Limits Manufacturing

The threat of pests to crop production is enormous. According to FAO, if pesticides are not used, the yield reduction rate caused by insect pests and diseases can be up to 53.4%, and the yield reduction rate caused by weeds can be up to 21.3%. 

In China, if pesticides and other plant protection approaches are not applied, the annual yield loss is more than 15% of the total yield. Biochemical pesticides, as a sustainable and efficient type of pesticides, have gradually become a research hotspot, and their development in China has also attracted much attention.

Definition and Classification of Biochemical Pesticides

China has no unified definition of biopesticides, and China's current regulations on pesticide registration do not have a clear definition of biopesticides either. However, in 2017, China defined biochemical pesticides as: biochemical pesticides should be natural compounds; if they are artificially synthesized, their structure should be the same as natural compounds. For example, the molecular structure of the main component of the synthetic compound is the same as the molecular structure of the naturally occurring analog. Since 2019, biochemical pesticides have been added to the classification of biopesticides in the Chinese regulation (previously, there were only microbial pesticides and botanical pesticides in the biopesticides, and agricultural antibiotics are still not included in the scope of biopesticides since the regulation adjustment in 2019.).

Although the development of biochemical pesticides in China started late, it has excellent potential. As of July 31, 2024, there were 152 active ingredients of biopesticides registered by the Ministry of Agriculture and Rural Affairs (MARA), of which biochemical pesticides account for about 36%, microbial pesticides account for about 45%, and botanical pesticides account for about 20% (Figure 1). Although the number of active ingredients in biochemical pesticides is relatively small, their registered products account for the highest proportion in biopesticides. [1]

Figure 1. Proportion of active ingredients in biopesticides registered in China (as of July 31, 2024)

The biochemical pesticides registered in China include five categories: insect growth regulators, semiochemicals, plant growth regulators, plant elicitors, and others, with a total of 54 active ingredients (as of July 31, 2024). Among them, there are only two insect growth regulators registered as biochemical pesticides: muscalure and S-methoprene; there are 15 active ingredients of semiochemicals, which are all insect sex pheromones, to control Spodoptera frugiperda, Chilo supperssalis (Walker), Spodoptera litura, Ceratitis capitata, Apolygus lucorum, Grapholitha molesta Busck etc.; plant growth regulators include 26 active ingredients, such as gibberellic acid and indolebutyric acid; plant elicitors include 10 active ingredients, such as harpin protein and lentinan; in addition, there is cholecal ciferol. The proportion of the active ingredients in the five categories of biochemical pesticides is shown in Figure 2.

Figure 2. Proportion of active ingredients in biochemical pesticides registered in China (as of July 31, 2024)

Current Status of Biochemical Pesticide Industry

The top five biochemical pesticide active ingredients on China’s production are gibberellic acid, oligosaccharins, brassinolide, triacontanol, and 14-hydroxylated brassinosteroid, accounting for 71% of biochemical pesticides. [2] Table 1 shows the number of registered biochemical pesticide products containing these ingredients in China (as of February 18, 2025).

Table 1. Number of products registered in China (Source: ICAMA)

The biochemical pesticide market is highly competitive, but some companies with innovations have strengthened their market position.

Pherobio Technology Co., Ltd. supplies the country's first registered Chilo supperssalis (Walker) pheromone products in China. This product slowly releases high concentrations of the sex pheromones in the field to cover up the location of female insects, making it difficult for the males to find the females to mate, which can significantly reduce the oviposition and the pest population. The current products include slow-release packets, dispensers, and others. The packet is the only slow-release packet independently developed in China which has a lasting efficacy of more than 4 months. It is very easy to apply the products, reducing the use of pesticides and saving labor costs. Its integrated control solution for rice with this Chilo supperssalis (Walker) pheromone as its core technology was listed in the key promotional technologies by MARA in 2024.

Indolebutyric acid produced by Zhengzhou Zhengshi Chemical Co., Ltd. is characterized by being environmentally friendly, high purity, and high efficiency. The company uses enzyme-catalyzed directional synthesis technology and continuous flow microchannel reactors to achieve the purity of indolebutyric acid ≥98.5% (the industry generally has a purity of 95%). It has been certified by HPLC and GC-MS. The gel filtration chromatography technology they use can reduce isomeric impurities and increase yield by 12%. It also can reduce 30% energy consumption compared to traditional processes. The enzyme-catalyzed directional synthesis technology significantly improves the efficacy and stability of the technical product. Zhengshi Chemical has replaced benzene solvents with bio-based solvents and built a recycling production system, achieving 98.7% solvent recycled, reduced industrial emission by 75%, and has been certified by REACH authentication and OECD ecotoxicity testing. The entire process, from raw material to end users’ application, is traceable and in line with FAO/WHO standards. Their indolebutyric acid has been exported to more than 12 countries in Southeast Asia, South America, and other regions.

Beyond Limits Manufacturing Changes Biochemical Pesticide Production

Biochemical pesticides have the advantages of high safety (no/low toxicity), low dosage (high efficacy), ecological safety (low residue), and precise biological regulation. However, they also face some challenges in their mass production, complex ingredients, inconsistent quality, and solubility. These problems need to be solved through molecular design, formulation technology, manufacturing processes, and application methods.

In September 2018, China created the concept of "Beyond Limits Manufacturing." This process uses femtosecond lasers to manufacture new chemical or biological components, making component discovery and production more efficient. [3] East China Normal University has built an ultrafast laser system and created a microfluidic chip. East China University of Science and Technology evaluated the design.

In traditional chemical production, the molecules involved in the reaction are in a disordered state in large pipes or other large reactors, and it isn't easy to improve their efficiency of momentum transfer, heat transfer, mass transfer, and chemical reaction (three transferences & one reaction). However, the principle of Beyond Limits Manufacturing is that when the diameter of the pipe that transports the reactant becomes thinner at the micron level, especially as thin as about 200 nanometers, the molecules can only move forward in the same posture due to the narrow space (Figure 3). By changing the pipe environment, different chemical molecules can meet in the micro/nano space in the posture that is most suitable for the "three transference & one reaction." In this way, the reaction condition is milder, the reaction rate is greatly improved, and the product purity is higher, making the manufacturing more energy-saving and eco-friendly.

Figure 3. Schematics for the evolution of the flow reaction in distinct flow environment. The color distribution in the flow environment represents the concentration distribution. (a) On a flat plane. (b) In a macro-scale tube (>2000 μm). (c) In a micro-scale channel (0.2–2000 μm). (d) In a nano-scale channel (<0.2 μm). [4]

Beyond Limits Manufacturing is of great significance to the biochemical pesticide industry and even to the entire process industry. It will subversively change the macroscopic form of traditional industries through large-scale miniaturization and integration at the micro/nanoscale. It is similar to the computers that have evolved from behemoths covering an area of 170 m² and weighing 30 tons to current wearable ones with performance increased by hundreds of millions of times. Chemical synthesis will also evolve from industrial parks to continuous flow microreactors and even micro/nanodevices. [5] This will not only bring about a significant improvement in productivity but also lead to a more sustainable and low-carbon footprint production. 

Beyond Limits Manufacturing is the key to promoting the industry to enter the quantum era. With the emergence of the second quantum revolution and artificial intelligence (AI), the electronics industry has approached this era, and the process industry is also looking for opportunities to enter. Beyond Limits Manufacturing enables humans to manipulate different particles at the micro/nanoscale and improve reaction efficiency and product quality, promoting the process industry to enter the quantum era with micro/nano effects and giving the industry a head start in global competition.

Cases of Beyond Limits Manufacturing Applied in Biochemical Pesticides

Beyond Limits Manufacturing's micro/nano fluidics technology has achieved remarkable results in the development and application of biochemical pesticides. Traditional spinosad suspensions and RNAi pesticides have some problems. After being improved by this technology, they have excellent performance, opening up a new path for the development of biochemical pesticides. [3]

Nano spinosad suspensions based on Beyond Limits Manufacturing micro/nano fluidics technology have shown excellent performance. With traditional production approaches, spinosad suspensions are not ideal in terms of storage stability, uniformity, and dispersibility, which affect their insecticidal efficacy. The nano spinosad suspension by Beyond Limits Manufacturing shows good storage stability under low temperature, room temperature, and high temperature. Even after repeated freezing and thawing 5 times (-20℃- 45℃), it still has good uniformity and dispersibility (97 nm, PDI<0.1), and its insecticidal efficacy is also better than the spinosad suspension available in the market. (Spinosad is an agricultural antibiotic that should be classified as a biochemical pesticide.)

RNAi pesticides, as a new type of biochemical pesticide (currently, no such product has been registered in China), have broad application prospects, but they have the problems of low stability of dsRNA and difficulties in efficient delivery and low-cost, large-scale synthesis. Nano RNAi pesticides based on the Beyond Limits Manufacturing micro/nano fluidics technology use lipid nanoparticles to encapsulate and deliver dsRNA (dsRNA@LNP). Through the continuous process, the lipid flow on the liquid surface is greatly improved so that the uniformity and dispersion of the dsRNA@LNP particles are good.

In addition, with the new RNAi pesticide chassis technology, the ingredients can be folded into nanostructures with specific shapes and sizes by base-specific recognition. It can be assembled based on any sequence or coding RNA and has good compatibility; compared to ordinary RNA, it has more substantial stability, good biocompatibility, and is easy to apply. This technology has changed the manufacturing method of traditional dsRNA pesticides. The coding sequence is firstly synthesized into ssRNA, and then self-assembled to form a specific nano structure of dsRNA. Its targets can be expanded. It enters cells through pinocytosis to silence target genes. There is no need to introduce nanocarriers. It can be directly sprayed and used and is safe and eco-friendly.

Prospects of the Biochemical Pesticide Industry in China

The future of China's biochemical pesticide industry will usher in breakthrough development driven by innovations and transformation toward sustainable agriculture. Biochemical pesticides, as an essential link between efficient farming and sustainability, will further enhance their strategic position.

The application of Beyond Limits Manufacturing has injected new vitality into the development of China's biochemical pesticide industry. This technology will continue to promote the R&D and production of novel biochemical pesticides and improve product performance. With the advent of micro/nano factories, relevant policies will be gradually enhanced to adapt to the industry's rapid development. 

In the global competition, China is expected to take the lead with the dual advantages of technologies and policies. Technology export under the initiative "Belt and Road" can transform mature solutions, such as insect pheromones and plant elicitors, into international standards. In addition, the EU's initiative "Farm to Fork" restricts the use of chemical pesticides, which also brings historical opportunities for the business expansion of Chinese biochemical pesticide companies. Through partnerships in R&D and production, the industry will continue to promote the transformation of global agriculture toward sustainability.

References

[1] Journal Pesticides, Volume 1, 2025

[2] Chinese Journal of Biological Control, Volume 5, 2019

[3] Fellow Qian Xuhong's report "Biochemical Pesticides and Beyond Limits Manufacturing" at the 4th Conference organized by China Association of Pesticide Development and Application 

[4] Liu P, Zhao F, Zhang J, et al. Micro/nano flow chemistry by Beyond Limits Manufacturing[J]. Chinese Chemical Letters,2024,35(05):29-38.

[5] Beyond Limits Manufacturing originated in Shanghai and is becoming a reality: In the future, an industrial park may only need one floor. Source: WENHUI DAILY 

This article was published in the "2025 China Pesticide Industry Watch" magazine. To read more articles from the magazine, please click the picture below.