Are New AIs On The Rise?

Attendees of CropLife America’s Spring Conference got some interesting news this year: The number of active ingredients (AIs) in basic manufacturers’ pipelines rose to 39 in 2014.

Though a far cry from the 70 AIs in development in 2000, it is a positive sign considering only 28 AIs filled the pipeline four years ago. “The numbers entering development have been on the increase since 2012,” said Matthew Phillips of Phillips McDougall, the agribusiness consulting firm that surveyed five basic manufacturers for CropLife America.

Why the uptick? It’s probably due to “a little bit of luck” but also the last six to eight years (until recently) “were some of the best years in ag ever,” said Jonathan Sweat, director of BASF Professional & Specialty Solutions. As such, manufacturers put more money into developing AIs for crop protection. At BASF, “we continue to invest at higher rates in this area” and “I think it’s really starting to pay off,” he said.

Basic manufacturers develop new AIs to address specific pest threats, insect resistance issues, price pressures from post-patent products, and increasing regulations and product restrictions. It’s an ongoing cycle: chlorinated hydrocarbons were replaced by organophosphates, which were replaced by pyrethroids; the “soft” products of today will be replaced by softer products going forward, explained Mark Boyd, president of Control Solutions.

While many AIs in the pipeline are likely herbicides and fungicides, some of the insecticides eventually could make their way into PMPs’ hands.

THE DEVIL’S IN DISCOVERY. Creating an AI from scratch is a complex and expensive process that takes about 11.3 years and starts with screening nearly 160,000 molecules (up from 52,500 in 1995), according the Phillips McDougall report.

Technological advances mean more molecules can be screened and today they’re evaluated for both crop and professional pest markets at the same time. “Very early in the development of the AI we would be assessing the fit in our market and putting resources toward it accordingly,” explained Sweat.

But few AIs are developed specifically for professional pest control due to market size. Many products in this market have less than $10 million in sales, said Paul Simons, global business director of Dow AgroSciences’ Urban Pest division, in a statement. With the cost of AI development topping $286 million (up from $152 million in 1995), according to the Phillips McDougall report, a novel compound usually needs the backing of the much more lucrative agriculture market to become commercialized. One exception is noviflumuron, registered in the U.S. only as a termite bait for Dow AgroScience’s Sentricon Termite Colony Elimination System, he said.

It also is “getting harder to find novel compounds that can make it through all the steps that you need to get through to ultimately get an active ingredient registered” in the U.S. and European Union, said Steve Gullickson, president of MGK.

Pat Willenbrock, head of marketing for Syngenta’s Professional Pest Management division, agreed. In trying to anticipate EPA demands, “we try to screen early” and “fail fast” with molecules, she said. Anything that’s a potential red flag gets killed early as it’s too expensive to pursue compounds that eventually won’t pass registration.

“It’s a gamble,” said Boyd. “The cost of failure is astronomical.”

The time and cost of bringing an AI to market have increased mainly because regulators now require more and different kinds of studies, such as those addressing environmental fate.

Even after passing all the tests, an AI may not get the go-ahead for professional pest use. “Our ability to model risk is improving all the time” and manufacturers may not expand an AI’s use if the risk/reward is too high, said Gullickson. “It gets too hard to find a safe use in every potential market and so you skip some,” he explained. As a result, “some products are becoming more specific for certain markets,” he said.

As such, you need “large organizations that can stomach that type of risk,” said Sweat. “At any one time, we may have eight to 10 active ingredients in development so think about the total scope then of the dollars that are associated. You’re talking in the billions. A small company just can’t do that,” he explained. BASF, Sweat said, invests $2 million daily in basic R&D.

Large and mid-size manufacturers plan to increase R&D spending 23 percent by 2019, according to a separate Phillips McDougall survey of 11 manufacturers for CropLife America.

Basic manufacturers generally discover and synthesize compounds from scratch but may license or buy them from third-party researchers. They also collaborate with external research organizations, like universities and research institutes. Syngenta works with 400 such groups. “Science is progressing in leaps and bounds” and “you have to cast your net wide to look at all these technologies, all these potentials, and you can’t bet everything on one note” said Willenbrock. Syngenta invested $1.4 billion in R&D in 2015, about 10 percent of sales, she said.

Mid-size manufacturers typically license or buy already discovered AIs and focus on completing the field testing and toxicology packages required for registration. Some mid-size companies specialize in bringing off-patent products to market.

FOCUS ON FORMULATION. While new AIs are important, they’re only part of the innovation equation, said Ildem Bozkurt, head of U.S. Professional Pest Management & Vector Control for Bayer Environmental Science. An AI’s performance strength “is contingent on optimized formulation and delivery and quantifiable measures such as speed to impact, residual duration and attractant properties,” she said.

Market-specific formulations must take into account the nuances of urban insect behavior, as what works on tomato or cotton pests probably is not going to work as well on ants or roaches.

As such, Bayer scientists created a formulation of Maxforce Quantum liquid ant gel bait that is effective at mega colony control and a bait matrix for Maxforce Impact designed to break the cycle of cockroach bait aversion. Research during the development of Temprid insecticide led to a “unique breakthrough” that fuses imidacloprid and beta-cyfluthrin together so each molecule is a compound of dual power for more effective control of hard-to-kill pests, Bozkurt added. And a polymer developed to protect pyrethroids for controlling malaria-carrying mosquitoes in Africa’s harsh environment now ensures the long-lasting effectiveness of Suspend PolyZone for PMPs in the U.S., she added.

A product is many things, reminded Willenbrock. It’s the AI, the formulation, the packaging, the marketing and being able to produce it cost effectively. Demand CS, for example, has remained a top product for 30 years by undergoing continuous innovation in all these areas, which ultimately makes “the customer experience better,” she said.

Manufacturers also add value by helping PMPs improve their product delivery, sales, marketing, safety and strategic business planning. BASF, for instance, designed a high-precision device that injects Termidor HP liquid termiticide into the ground, eliminating the need for trenching.

TOMORROW’S AIs. So what can PMPs expect looking ahead? “I think there are going to be a lot of really cool solutions that come into the pro pest marketplace over the next decade,” said Gullickson. MGK plans to introduce new momfluorothrin products next year and a new-mode-of-action AI in the next six.

PMPs can expect “safer and less toxic products” as “technology takes the next leap,” especially in product formulation and delivery enhancements, said Pramod Thota, global business director, FMC Specialty Solutions. He cited FMC’s “rich pipeline of more than 10 synthetic and biological active ingredients that we expect to commercialize over the next seven to eight years.”

“There’s a lot of interesting technology in the world that’s outside” the scope of developing conventional synthetic pesticides, said Cisse Spragins CEO of Rockwell Labs, which rolled out three botanical products in its EcoVia line earlier this year. Biological products are getting lots of attention. On the far horizon is RNAI (RNA interference) technology, for which “this marketplace is being considered as a potential outlet,” said Jeff Alvis, business manager of environmental products, AMVAC.

The outlook for conventional AIs is more cautious. “I would expect the number of new AIs in the market to continue to be relatively low” given industry consolidation and increasing regulations, said Sweat. “It’s only getting more difficult to bring new products and new active ingredients to the market.” This makes it “more important than ever that we steward the products” we have, he said.

That also means supporting product use across all segments, such as for lawn, golf and retail, added Karen Reardon, vice president of public affairs at Responsible Industry for a Sound Environment (RISE), which represents manufacturers, formulators and distributors of specialty pesticides. “We all have to be mindful in having our voice heard in the conversation out there to ensure that we have the technology we need,” she said.

The author is a frequent contributor to PCT.