The process for developing crop protection products

The crop protection industry exists and thrives because it is the only way growers and farmers can reasonably be certain of a harvest. This is due to two main factors.  Firstly, plants, like all living organisms, get sick and need to be treated. Secondly, without direct human intervention, most orchards, crops and paddocks would eventually be overrun by weeds, shrubs and trees that do not produce food.

Farmers apply crop protection products (CPPs) in order to manage or eradicate pests, and to maintain, promote, or regulate plant productivity. In an analysis of yields in various crops such as rice, wheat, barley, potatoes and coffee, the use of these products prevents yield losses of, on average, about 30 percent.

These products are derived from an understanding of the biological processes that occur in a plant or pest, identifying the critical biological processes in a target plant or pest that are essential for it to thrive and gaining control of it using a chemical or biological agent. This is what’s known in the industry as the search for the proverbial needle in a haystack.

Hundreds of thousands of potential candidate molecules are checked for activity in a tiered approach. The initial checking is through a high throughput screening, an automated process in which the molecules are assessed for activity in a controlled environment with minimal human contact.

Molecules showing potential are selected for progressively higher tiers of testing. On average the crop protection industry screens 160,000 molecules to find just one that is sufficiently able to control the target plant or pest while meeting all of the requirements regarding human and environmental safety as well as commercial considerations.

At the start of the process, chemicals are tested for their effects on people and the environment. This testing is agreed at the Organisation for Economic Cooperation and Development (OECD) level. Regulators from OECD countries – including New Zealand – participate in designing, validating and issuing guidelines.

The OECD has ten guidelines to assess the properties of crop protection products. This includes testing the efficacy of a molecule against the target pest or disease, its residue levels in plants and animals, and how the active ingredient breaks down in plants and livestock[D1] . New molecules undergo over 150 safety studies using internationally agreed test methods. For testing, concentrations are much higher than real-world exposure.

Accepted internationally as standard methods for safety testing, the Guidelines are used by professionals in industry, academia and government involved in the testing and assessment of chemicals (industrial chemicals, pesticides, cosmetics, etc.)”.

The guidelines fall into five categories covering their physical and chemical properties, effects on biotic systems, environmental fate and behavior, health effects and other test guidelines, including those addressing field trials and metabolism in plants and animals.

To examine the fate and behaviour of the molecule in the environment, there are 23 different test guidelines. The tests cover parameters such as bioaccumulation potential, rate of transformation and breakdown of the molecule in sunlight, in soil tests enable regulators to determine what is likely to happen to the molecule once it has been sprayed.

To assess potential health effects, there are a total of 77 different tests. The tests cover various endpoints in mammals, such as effects of acute exposure via the oral, dermal or inhalation routes, skin irritation, potential for causing allergic reactions, eye irritation, potential to damage DNA, potential to affect reproduction or development, potential to cause cancer, effects on organ systems from long term exposure and other endpoints. Results from these tests allow regulators to determine the risks a molecule potentially poses to operators, bystanders, consumers and animals.

The safety tests can be thought of as an array of ‘gates’ or hurdles which candidate molecule must pass. Some gates can be viewed as critical pass/fail hurdles, whereas others serve as alerts for further investigations. For example, if a molecule was found to directly damage DNA, then it is unlikely any company would find grounds for proceeding with such a candidate, even if it demonstrated extraordinary levels of efficacy. On the other hand, a candidate showing impacts on non-target plants, could still be progressed if the envisaged use will not result in unacceptable exposure of non-target plants.

So if a candidate fails a critical hurdle, industry practice is to drop the candidate in order to avoid spending millions of dollars on a molecule that will not be able to pass the regulatory review.

The test guidelines are under continuous review to take into account new knowledge, technologies and practices, and new guidelines are also issued as needed. Therefore, the rigour of the safety testing regime continues to become more and more stringent. The result is that the number of molecules that need to be screened and the amount of time it takes to find a suitable candidate are both increasing rapidly. According to CropLife, it now takes 11 years and US$286 million (>NZ$400 million) to bring a single crop protection product to the market.