​Stepan Agricultural Solutions: Unlocking the Power of Biological Active Ingredients Through Formulation Technology

Alexander Nikoloff, Senior Microbiologist, Stepan Company

James Sawyer, Global Business Development Manager, Stepan Company

Biologicals In Agriculture

As the agricultural world continues to shift toward sustainable practices, biologicals will play a key role. To date, the biologicals market's growth has been impressive, from $2B USD in 2012 to an estimated $9B USD in annual revenue today.¹ Drivers contributing to this continued growth are increasing environmental regulations, reduced pesticide usage and consumer demand for organic produce. These drivers, in combination with the fact that biologicals represent only a small fraction of the overall agricultural inputs market, suggest significant potential for growth.

Focusing on crop protection, one opportunity for the adoption of biologicals by growers is through using conventional and biological products in a rotational strategy. This leverages the individual attributes of each. For example, with biopesticides, implementing integrated pest management (IPM) practices have demonstrated advantages in mitigating resistance issues and addressing consumer demand for pesticide-free food through late-season applications. However, for biologicals to continue to see an increase in demand, they will need to address some of the real and perceived limitations:

• Lack of formulation stability resulting in separation and inconsistent application

• Poor active stability resulting in short shelf-life and sometimes the need for cold storage

• Inconsistent performance in the field driven by environmental factors

• Misaligned agronomic performance (high cost vs. yield uplift)

The utilization of formulation technology with biological products offers the potential to address these challenges and achieve enhanced bio-efficacy.

Biological Solutions of Interest

Biological products are naturally-occurring microorganisms and substances that, when applied as part of regular agronomic practices, provide benefits as biopesticides, biostimulants or biofertilizers.

• Biopesticides control pests and diseases

• Biostimulants support plant natural processes to mitigate stress and/or enhance overall health

• Biofertilizers increase the supply and availability of nutrients 

From a composition perspective, biologicals suitable for formulation can be grouped into three broad categories: biochemicals, minerals and microbials. For clarity, it should be noted that plant-incorporated products (i.e., Bt corn) and beneficial macrobials (i.e., parasitic arthropods) additionally find significant use in production. However, as these are not suitable for formulation, they will not be discussed further. 

Categories requiring formulation technology include: 

• Biochemicals (i.e., metabolites, botanicals, pheromones, allelochemicals)

• Substances of mineral origin (i.e., copper, sulfur)

• Microbials (i.e., bacteria, fungi, viruses, nematodes, protozoa)

Based on their inherent properties, each class of products brings unique challenges and limitations that the formulator must address during product development. The recommended formulation type, selection of co-formulants, and level of complexity will vary.  Fortunately, we can draw on the historical formulation knowledge from the development of conventional actives and chemical substances in the case of biochemicals and substances of mineral origin. 

Microbes present a completely unique set of challenges in that they must not only be formulated into a physically stable solution but also must, at a minimum, be kept sufficiently viable and non-inhibited to enable efficacy when deployed in the field. To complicate matters further, microbes are distinct in that types of microbes (i.e., bacteria vs. fungi), different forms (endospores vs vegetative; conidia vs mycelium), or even variation in microbial strain can require utilizing significantly different formulation technologies to preserve microbial viability and biocompatibility. For this reason, it is essential to have a fundamental understanding of not only the microbe and associated components from production, but also how these interact in combination with the co-formulants and additives in the final formulation.

Stepan Agricultural Solutions’ Approaches to Biological Formulation

Based on the complexity of formulating with microorganisms and multiple factors that must be considered, it can be difficult to know where to start in formulation development. To address this, there has been an effort made to promote the idea of ″chassis″ formulations that microbes can simply be added to the chassis to achieve a viable and stable formulation. While this approach can sometimes be successful, it comes with significant trade-offs, including a lack of fundamental knowledge of the formulation components and a lack of flexibility enabling specific formulation attributes. This hinders the formulator’s ability to build second-generation products that incorporate additional actives or offer formulation advantages. For this reason, Stepan Agricultural Solutions has taken an alternative approach to customized microbial development.

Figure 1. Stepan Agricultural Solutions’ Commercial Formulation Process

Leveraging this approach, formulators are empowered to develop robust formulations capable of handling process variability while meeting the end market demands of growers. Execution of the process starts with microbial actives and ends with the commercial formulation designed to meet market needs. A simplified decision sequence illustrated above outlines the basic considerations that must be made in the development process.

• Biocontrol: Identity and define attributes of the microorganism or consortia of organisms; determine the concentration target; understand product variability and impurities

• Application: The product can be applied in different ways depending on desired performance and in-field constraints; decisions between foliar, soil, or seed application; consider paired application technology that will be used in the field

• Formulation: Type of formulation related to constraints of the active ingredient and alignment with grower preferences; additional consideration for other components in the tank and potential interaction

• Co-formulants: These are the building blocks of the formulation and must be compatible with the active; key considerations include the need for Organic Materials Review Institute (OMRI) listing; potential need for regional modification, hazard classification, and biocompatibility

• End Product: The final commercial formulation that will be provided to growers and the summation of previous steps; target attributes such as physical formulation stability, ease of use, extended shelf-life, and enhanced efficacy

Understanding the Microbial Demands

As a project enters into formulation development, it is imperative to understand and account for the needs of the microbe species and in many cases the specific strain being formulated. This includes when the active is in the concentrated in-can form and upon dilution into the tank for application. The sensitivity of the microbe to moisture is particularly important to consider as failure to control water availability can result in premature germination that can reduce shelf life and negatively impact the viability of the product at application.

To assist in development, a number of analytical tools are available to provide insight into the interaction between co-formulants and microbials. The most basic among these is the paper disk Zone of Inhibition (ZOI) test, which has gained favor based on its simplicity, wide use in medical microbiological settings, and easy visualization of data output. As demonstrated below, a clear area between the treated disk and media indicates incompatibility of the co-formulants with the microbiologic tested.

Figure 2. Illustration of Zone of Inhibition Test for Microbial Compatibility

While ZOI testing provides basic compatibility information, translation of the results to a final formulation is not always successful due to the limitations of ZOI testing. Alternatively, the use of Minimum Inhibitory Concentration (MIC) testing can address some of these challenges; however, the data output is still challenging. To address these challenges, Stepan Agricultural Solutions has leveraged our in-house microbiology expertise to pioneer the Biological Compatibility Assay (BCA) that uses high throughput analysis to provide accelerated data collection and a broader depth of relevant agriculture information. Central to the BCA analysis, is the adaptation of a well-established resazurin technology, which provides valuable information on the compatibility and viability of microbials both in the concentrated formulation, as well as in the spray tank. Demonstration of this methodology for a wide range of microbial types and forms, with a range of co-formulants, has successfully been completed. Furthermore, advanced biological characterization techniques have been developed to address robust and holistic analysis of formulation stability data parameters. 

Figure 3. Stepan Agricultural Solutions’ Next Generation Biological Compatibility Assay 

The application of biocompatibility testing and advanced biological characterization techniques to additional areas remains ongoing, with exciting developments demonstrating the power of microbiology technology innovation. For example, the determination of biological compatibility in the presence of alternative crop protection products provides guidance on potential tank-mix partners as well as valuable insight needed for the planning of costly agronomic studies. Additionally, characterizing the changes in a microbiologic within a formulation matrix, while undergoing stability testing, can give a unique perspective of benefits and improvement opportunities. 

Establishing the Formulation Toolbox

Formulation development starts with having the available co-formulants needed to build the desired properties and functionality into the final commercial product. This collection of co-formulants currently available for use in development is commonly referred to as the ″formulator’s toolbox.″ While variations exist based on formulation type, common components are summarized in Table 1.

Table 1. Summary of Common Formulation Components

While this collection is well established for chemical actives, the same is not true for biologicals where unique challenges exist associated with keeping microorganisms viable and non-inhibited. To address this challenge, Stepan Agricultural Solutions is leveraging several innovative technology platforms to create the first-generation Bioformulator’s Toolbox™ for use in microbial development. Additionally, we are actively working to expand our expertise in this area by developing novel technology to address challenges with co-formulant incompatibility as well as partnering with companies to accelerate their projects from development through commercialization.

The Organic Paradigm

A key question that must be addressed in the development process is whether or not the development of a product approved for use in organic farming is required. Today, the organic production segment has significant value and is a key target for the majority of microbial products that are brought to market. The selection of co-formulants in North America is commonly aligned with the National Organic Program (NOP), with many companies preferring a review by the Organic Materials Review Institute (OMRI) that determines allowed ingredient use in organic production and processing. To help formulators navigate this space, Stepan Agricultural Solutions offers an OMRI-listed ECOSTEPTM line of wetting agents, emulsifiers, dispersants and carriers.

Partner with Stepan to Grow Through Science

Stepan Agricultural Solutions is committed to collaborating with agricultural companies and growers to support the continued growth and advancement of biological and microbial formulations. Just as adjuvants have enhanced the efficacy and adoption of chemical crop protection, we believe they will be key to allowing biologicals to maximize their potential in agriculture. Our global team is dedicated to cultivating excellence by partnering with our customers to explore new technologies and provide tailored solutions.

Our experienced team of chemists, formulators, microbiologists and business professionals work together to support the biological market by providing quality co-formulants, access to novel formulation technology and customizable development support. In the biologicals space, we partner with customers to meet their specific needs by offering everything from development materials and guidance, to contract development services through our Advanced Formulation Services.

Stepan Agricultural Solutions is here to help you grow through science.

¹Farm Foundation^®, (2021, June 29) Farm Foundation Forum: Biologicals in Agriculture: Innovation, Science and Promise [Video]. YouTube. https://www.youtube.com/watch?v=loZYjM7CrrI