Hear from our experts: Formulating biologicals

There is a shift in agriculture towards sustainable alternatives to traditional chemical products. Biologicals are one interesting option.

Biologicals are products with biological - as opposed to chemical - active ingredients. They can be microorganisms (such as fungi and bacteria) or large molecules (such as peptides, proteins, and RNA). These actives can be formulated into products including Biofertilisers (to promote growth), Biostimulants (improve plant resilience/enhance yield), or Biopesticides (kill pests).

That formulation is very different to chemical actives. Chemicals are created in a lab and designed to be stable. Biologicals, which are bigger and more complex, are adapted from nature, and are fragile. They can be killed, harmed, or broken down by heat, UV, moisture, or any number of naturally occurring microbes or enzymes. 

Biologicals will need many of the usual formulation ingredients: rheology agents, dispersants, emulsifiers, protective agents and so on. But extra care must be taken when selecting and formulating these ingredients, both to protect the biological actives from the environment, and to ensure those ingredients themselves do not cause harm. 

In our report, we look at the formulation challenges for a range of biologicals. In this blog, we will take a brief look at some of these.

Keeping microbes safe

Microbes can be applied to seeds as enhancements. They can also be formulated into sprays as foliar products. 

The first goal of formulating such products is not to kill the microbe in production. Many common ingredients can be toxic to biologicals, so there is a need to carefully select and test the right ingredients for the formulation.

Then, the goal is to keep the microbe inactive. If it is inactive, it will stay ‘asleep’ until it is needed. It will wake up if it has water to grow, and once it starts growing, it will exhaust its resource and die, unless it is already in the ground. So it’s critical to dry it quickly and store it in a dry place until needed. 

Seed treatment formulations usually involve integrating the active biologically, and the supporting formulation ingredients, into a liquid coating that will stick to the seed. These give a degree of protection, though thicker crusts can also be used if more protection is needed. 

Some foliar products need to be retained on a canopy, which means formulating ingredients that adhere to the leaf and provide UV protection, though others may be delivered via soil. Sprays do not have the option of a thick protective coating to safely wrap up the microbes, but many can be formulated into soluble powders and vacuum sealed, creating a safe, dry environment until they are ready to be dissolved.

The appropriate formulation will be different for every microbe, depending upon the microbe parameters, the seed it is applied to, the application method, and what it needs protecting from.

Delivering RNAi into the field

Large molecules are newer and more complicated. The big disruptive innovation in large molecule biologicals is RNA interference (RNAi). This involves delivering RNA into plant or insect cells, to exploit natural processes in order to silence a gene, for example a gene that expresses herbicide resistance, or disrupting the production of a protein that a pest needs to survive. It has the potential to be highly targeted.

Like many large molecule actives, the RNAi challenges are threefold: (1) delivering the payload, (2) keeping it safe and in place (eg on a leaf) between being applied and being absorbed or ingested, and (3) keeping it intact in storage. 

There are no ready-made answers and research is still needed to work out how to formulate these into deliverable products. As these develop, making them viable will depend upon formulating them into products that can be delivered into agricultural environments – this is an area of active research at Croda and others.

Testing biologicals 

Because of the complexity of biologicals, it is impossible to be completely certain of the effects of combining lots of ingredients. Therefore, everything needs to be tested. 

Firstly, each component of the formulation needs to be tested separately to assess biocompatibility – ie how it impacts the biological active, and at what concentration it might become toxic. 

Then we need to test everything together in the formulation. Some ingredients are fine on their own but create negative effects on the survival of the microbes when we blend them. If we rigorously test all ingredients separately, we can have high certainly that the blend will not cause harmful effects, but that is not 100%, so we need to test the final formulation too.

Conclusion: Getting the biological formulation right

Formulating fragile biologicals into a product that will sit on a shelf in uncontrolled conditions for months, and then be introduced into a complex real-world ecosystem, is a challenging task.

Doing this successfully in each case means exploring the full range of formulation options. It means looking at chemicals with different properties to explore which are best. It means drawing on expertise in formulation to put these parts together in a way that protects and enhances the biological, and does not cause it harm, whilst also being sustainable, scalable and cost-effective. And it means rigorous testing of the formulation to ensure it does what we want it to.

In our new whitepaper, Formulating Biologicals , we discuss the issues raised in this blog in more detail, propose solutions, and raise issues that need further discussion and exploration.

How Croda can help

We bring a strong understanding of formulating biological and chemical products for delivery into agricultural settings. We have a vast library of speciality chemicals that can help design sustainable formulations and delivery systems, and advanced testing facilities for biologicals. 

But we are also on a journey in this new area, and we want to hear from people with biologicals they are struggling to formulate, and from people developing formulation solutions, so we can all come together to better understand and solve formulation challenges. Contact Steven Adams for more information.