Typically, around 10,000 compounds are tested before we find one that is able to pass all of the hurdles.
Ten years and $250 million. That’s what it typically takes to develop a herbicide, starting from the time an active ingredient is discovered to the time the product is registered. Herbicide development involves many things, including chemistry, biology, registration, regulatory science, supply, marketing, and beyond.
The process of creating a herbicide begins with the discovery of the active ingredient involves synthesizing thousands of molecules, and doing a range of preliminary tests to determine any potential activity. These preliminary tests are called screening tests – they include testing for biological efficacy as well as stability and toxicity.
Typically, around 10,000 compounds are tested before we find one that is able to pass all of the hurdles. Sometimes we are fortunate, as with the case of Axial. Syngenta scientists were investigating a compound for insect control when they serendipitously discovered a compound that was effective in grass weed control. Using this as a lead they screened 1,381 different compounds – a relatively small number – before identifying Pinoxaden, the active ingredient.
Once it is determined that the active molecules are biologically sound, they are tested for safety and performance. We experiment extensively with the molecule to see how it responds in different situations, and how it can be enhanced to work safely and effectively. Trials are conducted to test the weed spectrum and determine crop tolerance, so the efficacy of the active ingredient can be evaluated.
We also need to test the viability of the product by assessing the properties of the active ingredient: for example, if it’s water soluble, if it’s solid or liquid, and what its melting point is. This helps determine the final delivery form of the product, as well as any adjuvant that may be required. Grass weed herbicides often require an adjuvant in order for the active ingredient to penetrate into the weed. In the case of Axial, extensive lab tests and field trials led to the development of Adigor, an adjuvant that was designed to enhance the activity of Axial.
Extensive field trials are required to ensure the product will work over a range of real-life situations. In the case of Pinoxaden, we performed field trials in numerous cereal production countries around the world, with particular focus on Canada. The product must work just as well in the field as it does in the lab, both alone and with various tank mix partners.
Special challenge in Canada
Part of the development process is making sure that the product will function well within the Canadian climate. If the product is stored in a barn, it needs to withstand both extreme cold and extreme heat, which can amount to a temperature fluctuation between -40 C to +40 C.
Canadian products also need to withstand water temperature and quality differences. Water drawn from a dugout or deep well can be very cold, and spring-time watering can mean using water that is just above freezing.
Furthermore, the active compound must adapt to a practical formulation for producers – either a liquid or a granule that can be produced in large scale. The production requirements may mean the company making the product must build an entirely new plant, or adapt existing facilities for the production of the end use product.
Testing takes approximately three to four years. The product must undergo stringent qualification tests in many jurisdictions including Canada, the U.S., and Europe. The Canadian Pest Management Regulatory Agency (PMRA) requires information concerning a herbicide’s effects on human health, the environment, and its agronomic value prior to registering the herbicide for use.
The PMRA requires toxicological evaluation to establish the levels at which humans can be exposed to the products without any harm. This includes all sources of exposure, including applying the product, and consuming treated crops or livestock that have consumed feed originating from treated vegetation. Such an evaluation results in setting the Acceptable Daily Intake (ADI) – the amount of a compound that can be consumed daily for a lifetime with no adverse effects. ADIs always have safety factors built in, ranging from 100 to 1,000.
PMRA also evaluates data on the environmental chemistry and toxicology of products to determine what happens to the active ingredient once it enters the environment and its potential impact on wildlife.
The process can be lengthy. We discovered Pinoxaden in 1998 but it took until 2004 before we had all the data and testing needed to submit to the PMRA and its U.S. counterpart, the U.S. Environmental Protection Agency (EPA). A year later Axial was registered in both Canada and the U.S. – resulting in eight years from discovery to commercialization.