Future Requirements, Challenges and Core Competences in Formulation Innovation and Development

“Regarding the formulation technology innovation, an agchem company core competence should have the following strategies and objectives: 1) developing new pesticide molecules, 2) discovering new biopesticides, 3) design formulations of either single or combo AIs (both new and generic) with the aid of effective, safe co-formulants, and 4) manufacturing the resultant formulation products in a safe and cost-effective manner, which should be deliverable and efficacious for the farmers,” said Roy C. Chen, PhD, former ADAMA US Formulation Team Leader, in a recent interview with AgroPages.

He also shared his views on the future development trends of novel formulation and application technologies, regulatory and R&D challenges that affect formulation innovation and development, as well as core competence to drive formulation technology innovation.

Q1. What novel formulation and application technologies are needed to meet the needs for growers over the next 5-10 years in different global regions?

In the next 5 to 10 years, the worldwide population will demand more secure and reliable food crop production, in terms of quantity and quality, while adjusting to climate change and reduced arable land. The future of novel formulation technological development for agrochemical companies will center around developing not only new AI molecules by R/D companies, but also combo AIs, or so-called hybrid mixture formulations by most generic companies. The latter direction is due to the need to differentiate oneself  in local and global market places. Furthermore, there is also a desire to be environmental-friendly, while keeping safe and efficient applications, and breaking weed resistance, such as those of glyphosate and triazines, among others. Formulation technology could be part of an integrated approach involving a weeder machine, and crop rotations in conjunction with novel agri-formulations. How about using chemical/biological combo formulations to fight against resistance? For  example, one could use certain fungal spores in the formulation. The major formulation challenges lie in dealing with formulation mixtures which are becoming more complex, so do the coformulants needed to make that happen. Usually, these include new functional co-formulants, green solvents, biostimulants and other related adjuvants.

Q2. What are the regulatory challenges to affect future formulations? Could you share some specific cases of how  an agchem company develops agrochemical formulations suited to different global regions?

As national authorities manage formulation registrations individually, through various local laws and policies, agrochemical producers may face challenges in cases of the same co-formulants which may not be globally accepted. Therefore, separate versions of the same product formulations may be necessary, so do the corresponding tox data requirement. As a result, more resources are needed for registering the same product. By the same token, managing the downstream supply chain issues would be just as challenging and costly. Furthermore, due to different pesticide regulations among countries, there could be issues involving pesticides in international trade. A recent example concerns glyphosate re-registration in the EU. Because Glyphosate formulations, particularly those coupled with polyethoxylated tallowamine emulsifiers (POEA), have been shown to cause elevated cytotoxic or endocrine disrupting effects, compared to the active ingredient glyphosate. However, this is not an open and shut case for some. Opinions among scientific communities, health officials and environmental authorities/organizations are divided. Essentially, the case touches upon fundamental aspects of risk assessment and product regulation. A very recent news item is that a French court has issued a ban on glyphosate sales in France. Several other countries outside the EU, including Argentina, Australia, Bermuda, Brazil and Canada, are banning or restricting glyphosate use, while the US has not. Because of the glyphosate issues, the fate of POEA Tallowamine coformulant has also been affected. In response, Bayer/Monsanto, the glyphosate formulation manufacturer, is now removing the Tallowamine emulsifier away from all glyphosate formulations. There is also  movement in the EU to use alternative weeding methods, in addition to IPM techniques, plus using other safe organic herbicides, such as essential oils, acetic and citric acids, as well as  fatty acids, as in soap formulations which may be necessary to help manage post-glyphosate market needs.

Q3. What are the challenges in R&D for new formulations and possible solutions? 

In the broad background of satisfying the overall agricultural production needs in food, fiber and fuel crop productions, farmers usually rely heavily on agrochemicals in modern farming to enhance crop yield, increase plant growth, neutralize the soil, and protect against pests, including weeds, insects, and fungi. The issues are how to increase and optimize the agricultural output in each region through smart utilization of agrochemicals. The corresponding formulation R/D challenges resides in developing new combo formulations, which are  becoming more complex to formulate. Take a close look at potential formulation components that a formulator must face; including the chemical active ingredients, wetting agents, emulsifiers, surfactants, dispersants, polymers, solvents, oils, adjuvants, suspension aids, powders, buffers, rheology modifiers, water, adjuvants and more. Their physical and colloidal interactions with one another must be appreciated and acted upon accordingly. Obviously, the goal is to have an end formulation product which must be physically and chemically stable in storage, and easily applicable for tank mixing, while delivering the pesticidal efficacies. More challenging are those combos of agrochemicals and biopesticides. For example, there are biopesticides consisting of bacterial or fungal spores for seed treatments, combined with the chemical insecticide on crop seeds, such as corn, soybean, and cotton. The seed treatment combo formulations may be one of the reasons why the biopesticides market is growing. Prominent examples are BASF’s Poncho Votivo and PV 2.0 (nematicide) and Syngenta’s Clariva Complete (Soybean Cyst Nematicide).

Q4. Could you share some cases  of digitalization technologies that enhance efficacy for formulation development / application/ delivery?

As we are living in a digitized world, it is only natural that digital technology can be utilized or considered in agrochemical formulation development, such as data collection and organization for formulation definition and registration purposes. Databases of co-formulants, including their chemical and physical properties, can be searched for data mining. For now, there is still no computer modeling or simulation of agrochemical formulations. Actual formulations still need to be put together physically, according to compositions on the bench for realistic testing and monitoring. This is an area yet to be explored. 

A very useful statistical methodology applied to formulation development is the “Design of Experiment ” (DOE). It is a well-established systematic approach to create good formulations. There are commercial computer software packages marketed to perform formulation DOE. This statistical method is a powerful tool for formulation optimization, particularly when multiple ingredients are involved to achieve the final performing formulations. Generally, DOE technique is highly recommended, as most formulators have been trained or are used for employing traditional techniques of changing one-variable at a time (OFAT), versus something like factorial designed experiments through DOE techniques.

Other areas of agrochemical digitization start from digitizing lab formulation test equipment, which can be computer controlled and monitored, and examples include lab viscometer and incubators for freeze-thaw tests. Regarding the downstream agrochemical pilot plant operation and the further down-stream production, the associated digitization is expected to follow those of a digitized chemical plant, both in unit operation and unit process. From plant control panel to process unit feedback, modern digital technology can be a great tool, in terms of safety and good quality control. One critically new area for all agrochemical companies to consider is the formulation production simulation for formulation plants. Not only can a normal formulation operation be simulated, but also an inconceivable formulation mishap. A simulation software module can be a cost-effective training tool for pilot scale up and production crews. The final area to consider is formulation plant automation. This can be an effective way to increase productivity, minimize costs and make your facility operate more ergonomically. Plant automation should be well suited to a stepwise type of processing for a production facility which manufactures agrochemical formulations.

In the near future, delivering formulations to the field will be done by robots in modern farms, usually by Agbots plus flying drones. Accordingly, agrichemical formulations can have higher concentrations, while formulation types and design also can be more versatile, without human safety concerns. For the same reason, formulation sprays can be more flexible, as well.

Furthermore, formulation application can be performed in a high precision manner and be far less polluting to the environment.

Q5. What’s the core competence to drive formulation technology innovation in an agchem company? What innovation formulation technologies have been launched in the agchem industry? 

As far as a modern agrochemical company is concerned, regarding the formulation technology innovation, the company core competence should have the following strategies and objectives: 1) developing new pesticide molecules, 2) discovering new biopesticides, 3) design formulations of either single or combo AIs (both new and generic) with the aid of effective, safe co-formulants, and 4) manufacturing the resultant formulation products in a safe and cost-effective manner which should be deliverable and efficacious for the farmers.

Furthermore, regarding the formulation technology innovations necessary to follow up the above strategies, the agrochemical company needs to excel in the traditional formulation technologies such as the emulsifiable concentrate (EC), soluble concentrate (SL), suspension concentrate (SC), water dispersible granule (WG), and wettable powder (WP) by Improving and optimizing the compositions. Have a pipeline of formulation products each year for the market. Beyond the traditional formulations, other specific formulation types may be considered, such as suspo-emulsion (SE), oil dispersion (OD), and capsule suspension (CS) formulations utilized to deal with the specific cases including physical or chemical incompatibility, bioefficacy improvement, reduced environmental toxicity, etc. Typically, these formulation types require longer time to screen and test. Lastly in the case of microbial spore biopesticides, the up-stream fermentation excipients usually are mingled with the spores in the very formulation mixture, that can be a challenge to the formulators!