Discovering a new active ingredient, especially one with a different mode of action, has never been an easy task. How does a termiticide such as Altriset arrive on the market? Here we look at the long and challenging journey to bring a new product to market.
Whatever the industry, customers are always looking for the latest and greatest, the innovation that makes their lives easier or better. In the pest control world, coming up with new active ingredients, especially ones with a different mode of action, is actually a necessity to combat insecticide resistance. Discovering new active ingredients has never been easy, but with the increasing expectations around safety profile and environmental impact, bringing them to market is getting a whole lot harder.
A journey of discovery
When Syngenta’s termiticide Altriset was introduced to the market in 2011, it had taken significant development work to get it to the point of market introduction. To introduce a new active ingredient such as chlorantraniliprole takes around 10 years of development from start to finish. The journey began back in the 1990s when chlorantraniliprole (it only had a code number back then) was identified as a molecule of promise. If it was developed today, it would be one of 100,000 molecules actively screened each year. Molecules identified as ‘promising’ are then screened for activity and chemical properties; even fewer progress to the next stage of development.
Investing in development
The next stage is where the significant financial dollar and time investments are made. The critical component of this investment cost goes into understanding what the product does, and how it performs. Each product must go through several core areas: chemistry development (including process development and synthesis optimisation), biological development (including field and laboratory trials and validation), toxicology (including acute toxicity studies and non-target organism studies) and environment (including environment metabolism and residues). These aspects are important for performance and regulation compliance. Thirty per cent of the overall cost of developing a new active ingredient is now spent on product safety.
It’s through this stage that the key understanding of a product like Altriset’s active ingredient chlorantraniliprole is developed.
Trials in real world conditions
Laboratory trials are an important first stage of testing for all products, but substantial field efficacy trials are required to ensure products have the expected performance under a range of conditions. Altriset trials carried out in the USA and other countries may be used in support of a registration, but local work is a must for registration in Australia. Syngenta set up extensive field trials in Australia, both south and north of the Tropic of Capricorn, to challenge Altriset in Australian temperate and tropical conditions. But also to ensure Altriset performed in a range of different soil types and on local termite species.
Syngenta researchers created an extensive trial setup that consisted of a concrete slab construction to mimic a real life housing setup. It provided a more realistic challenge for Altriset, which is particularly important when assessing non-repellent chemicals. Each concrete slab setup contains treatments of either a vertical or horizontal barrier, or an untreated control. The slab on ground construction allows termites to access wood placed at the slab’s centre.
Termites can access the wood by building over the edge of the slab, or moving through a designed crack in the concrete – but they have to pass through the non-repellent Altriset treated zone first. By comparing concrete slabs with treated or untreated soil, the performance of Altriset can be assessed in real life replicated trials.
Trial setup for termiticides must stand the test of time to support ongoing registration. The trials have remained in place and have been used to support further label extensions.
Soil residue studies
Soil residue studies are carried out to confirm the persistence of the product and its long-term performance. This is critical to soil-applied termiticides such as Altriset, which is currently registered for eight years south of the Tropic of Capricorn and four years to the north. All Syngenta field efficacy trial layouts include ‘residue plots’, from which soil samples are collected each year, when the performance of the field trials is assessed. Residue analysis is carried out to confirm the quantity of Altriset still present in the soil.
Laboratory based ‘termite tube studies’ are carried out to support the field trials by demonstrating that the Altriset soil residues are sufficient to control termites and maintain an effective treated zone. Under standard laboratory conditions, termites are paced at one end of a tube and a food source is placed at the other end. The middle of the tube contains soil from the field trials, effectively creating a pressure situation where termites are compelled to travel through the barrier. This allows the researchers to establish mortality and time-to-mortality: a process that successfully supports and demonstrates how aged soil residues maintain their effectiveness as a non-repellent barrier. The trial design is replicated and contains controls of untreated soil to maintain scientific rigor of the results.
All of this testing data, along with the toxicology, safety and environmental data packages is presented as part of the registration submission package to the APVMA. Registration of a new product, one that uses a new active, can take around two years. It was no different for chlorantraniliprole; product registration for Altriset took a further two years, and another year for each extension of the label.
It is estimated that the development cost of a new active ingredient from initial discovery through to first registration, globally, is around US$300 million. A substantial investment for bringing new products and tools to the industry. When a pest manager purchases R&D products they are supporting the development of future tools and products for the industry, as well as the ongoing support and extensions of use.
Real house trials
Alongside the field efficacy trials, Syngenta conducted trials with pest control companies in termite-affected houses around Australia, to demonstrate the ability of Altriset to eliminate termites established in buildings. Treatments were applied by pest managers using different application equipment, under a range of different climatic conditions, soil types, construction types and against different termite species. The trials not only demonstrated the successful elimination of termite activity in the houses and structures, but yearly inspections also demonstrated ongoing protection. These trials not only gave the early users of Altriset confidence in its performance but also formed part of the registration submission for label extension purposes.
The research continues
Even after registration, research on Altriset continued and helped provide increased understanding of its exceptional level of insecticide transfer, and its unique stop feeding effect. Ongoing field studies have confirmed the duration of protection provided by Altriset.
Future-proofing our industry
Without innovation in our industry, regulatory pressure and resistance development will continue to reduce pest management options. New products are vital for the future. Syngenta is committed to this with $1.3 billion spent on R&D last year, and more than 5000 employees dedicated to research and innovation worldwide. It is committed to providing the innovations and products required to future-proof the crop and pest control industries.
Mike de Luca, Techncial Manager, Lawn & Garden and Professional Pest, Syngenta