iFormulate: The Challenges of Biopesticide Formulation

Aided by a favourable regulatory climate, as well as by concerns about conventional  pesticides, the biopesticide market continues to grow. The global market is projected to grow from USD 3.0 billion in 2018 to USD 6.4 billion by 2023¹. Alongside the increased use of biopesticides (and other bio-actives used for agriculture, such as plant growth regulators and biostimulants) have come developments of more effective Integrated Pest Management application methods which take into account the health of the wider ecosystem and of the possible environmental impact of using control methods. However, with a total pesticide market (i.e. including conventional chemical pesticides) of around USD 56 billion, there remains considerable potential for further biopesticide growth.

The definition of biopesticides is not standardised but they are usually defined quite broadly and include the following general categories:

•  Macroorganisms (e.g. insects, nematodes and other organisms that predate on pest species)
•  Microorganisms (e.g. bacteria, fungi and viruses that kill or inhibit pesticides via a number of mechanisms)
•  Naturally derived biochemicals (such as peptides or enzymes) or other biological extracts (such as natural oils).

As with conventional pesticides, biopesticides must be formulated to provide a usable product that performs according to customer needs. The main functions of formulation are:

•  To provide a finished product which is stable during manufacture, storage and use;
•  To provide a product which is convenient to handle and to use in the application;
•  To ensure that the full potential efficacy of the active ingredient is realised and that its delivery for maximum effectiveness is ensured;
•  To ensure that the product can be used in a way that is safe for the user and the environment, and that it complies with regulatory requirements;
•  To provide a robust process by which the finished product can be manufactured and packed with a low level of manufacturing defects.

So where do the challenges of biopesticides lie, and do these challenges present any barriers to their further growth? Taking the category of naturally derived biochemicals and biological extracts first, these can essentially be formulated in a similar way to conventional synthetic chemical actives. The main additional challenge is that these compounds tend to be less chemically and physically stable than synthetic compounds. Peptides and enzymes, for instance, are prone to denaturing when exposed to heat and may readily degrade in acidic conditions. Therefore, for instance, it may be necessary to use formulation technologies, such as microencapsulation, to protect and deliver the active ingredient effectively or to include a UV-stabiliser to protect the active ingredient against photo-degradation.

In all cases, one very critical task is to ensure that any co-formulants used (e.g. surfactants, oils, solvents, carriers, binders, fillers, humectants, preservatives, etc) are chemically compatible with the active ingredient. Stability apart, however, actives in this category of biopesticides can be formulated similarly to synthetic pesticides. The formulator then needs, first, to consider the key physical properties of the active ingredient when selecting the formulation type, e.g.:

•  Water-soluble actives may be formulated as soluble liquid concentrates (SL) or soluble granules (SG);
•  If a liquid product is desired, water-insoluble actives may be formulated (with an oil if necessary) as emulsifiable concentrates (EC), oil-in-water emulsions (EW) or microemulsions (ME);
•  Active ingredients which are solid at room temperature can be formulated as water-based suspension concentrates (SC) or may be combined with co-formulants to produce water dispersible granules (WG) or wettable powders (WP) which will disperse readily in a spray tank. If a fine particle size is required, usually only those actives which are heat-resistant and relatively high-melting can be milled before formulation;
•  Actives which are solid but are water-sensitive can be formulated as oil dispersion (OD) formulations which then require further emulsifiers in order to disperse the oil phase in the water of the spray tank;
•  As mentioned earlier, actives which need to be protected in some way or where the release needs to be controlled can be formulated as microcapsule suspension (SC) formulations.

However, the formulator has to consider the categories of biopesticides based on living organisms very differently from the naturally derived bio-chemicals described above. In the case of microorganisms such as bacteria, the objective is usually to ensure that the active organism is kept alive but in a dormant state during manufacture and storage, but on application it must be viable to then reproduce and become effective when applied to crops.

If the organism is not dormant in the formulation, then there is a danger that the culture will rapidly reproduce and consume any nutrients present and die out while still in storage. In addition, a living and growing culture can produce undesirable by-products, gas and odour during storage. For this reason, the simplest approach is often to reduce the water activity of the formulation to a low level, so that the organism will not reproduce on storage. Prior to formulation, the starting point is normally a water-based suspension of microorganisms. This suspension can be dried by methods, such as spray drying and freeze drying, in a way that does not cause heat damage. Then, solid final formulations with a low moisture content, such as granules (WG, GR) and powders (WP, DP), are often preferred. Additionally, to ensure initial microbial growth on application, nutrients such as carbohydrates may be added to the formulation.

On top of these considerations, the compatibility and stability of microbial actives need to be considered in the same way as for biochemical and synthetic chemical pesticides. So, the co-formulants used need to be assessed, with aggressive solvents and extremes of pH being things to be avoided.

Protection of microorganisms during formulation and afterwards can be enabled by the use of encapsulation technologies. There is a huge variety of possible methods to do this, here are just two interesting examples:
• The popular microbial biopesticide Bacillus thuringiensis (Bt) can be encapsulated, using a technique called Pickering emulsions, whereby emulsions are stabilised by solid particles². The resulting formulations were shown to perform better than conventional Bt formulations. The co-formulants used for the encapsulation were relatively innocuous, from a safety and environmental point of view (acrylic particles, sunflower oil, iron oxide nanoparticles, ethanol);

• The UV resistance of the fungal bio-insecticide Beauveria bassiana has been improved by the use of feruloylated soy glycerides (FSG), which were subsequently encapsulated in starch³. Additionally, soluble lignin was used as a spray tank adjuvant to protect against UV. Again, the use of environmentally benign co-formulants is favourable for the safety profile of biopesticides. 

Increasingly, bio-derived active ingredients are being formulated, together with conventional synthetic pesticides. One example of this is REGEV™ from STK. The two actives are a biofungicide based on a plant extract (Tree Oil or TTO), as well as difenoconazole, a conventional synthetic fungicide. The relevant patent⁴ claims that the TTO is delivered in the form of an oil-in-water emulsion. The patent also claims the use of TTO with a large number of fungicides – so perhaps further new mixtures are to be expected.

Biopesticides and conventional pesticides are also being formulated together in seed treatments. Poncho^®/VOTiVO^® (now being marketed and sold by BASF) combines the systemic insecticide clothianidin with Bacillus firmus I-1582 in a seed treatment. The clothianidin is immediately absorbed by the roots and the Bacillus firmus I-1582 forms a barrier around the seed. It is claimed that this protects against up to two generations of nematodes⁵.

In conclusion, the potential incompatibilities between conventional synthetic active ingredients and microorganisms, as well as other bio-actives, can clearly present challenges to the formulator - who may also have to deal with issues, such as UV-stability and the delivery of microorganisms. In addition to dealing with the usual challenges of efficacy and stability that the formulator has to handle for all kinds of crop protection products, it is clear that formulation will have a very significant role to play if the market for effective bio-control products is to continue to grow at a rapid rate.


1. Markets and Markets “Biopesticides Market” 2019 via www.marketsandmarkets.com
2. “Controlled-release of Bacillus thuringiensis formulations encapsulated in light-resistant colloidosomal microcapsules for the management of lepidopteran pests of Brassica crops”, Bashir et al, PeerJ. 2016 Oct 11;4:e2524. eCollection 2016.
3. “Improving Formulations for Biopesticides: Enhanced UV Protection for Beneficial Microbes”, Behle et al, in ASTM STP1527 “Pesticide Formulations and Delivery Systems, 30th Volume: Regulations and Innovation” 2011.
4. World Patent Application WO2013068961
5. BASF: https://agriculture.basf.com/us/en/Crop-Protection/Poncho-VOTiVO-2-0.html

This article was initially published in AgroPages '2019 Formulation & Adjuvant Technology ' magazine. Download the PDF version of the magazine to read more articles.