The regulatory waters for biopesticide candidates can be choppy. Here are some expert tips that may ease the journey.  

According to the Smithsonian Institution, 900,000 different species of living insects populate our planet, more than any other group of organisms on Earth. As if that number isn’t impressive enough, scientists estimate there are some 10 quintillion (10,000,000,000,000,000,000 in case you were wondering) individual insects alive at any given time.

About 99% these insects are beneficial to the environment, providing food for birds, fish, mammals, reptiles and other insects. Others are breathtakingly beautiful to watch, like the regal Monarch butterflies. But that still leaves billions of insects that injure humans, animals, crops and possessions, compete with humans and animals for food, and spread disease.

Countries tried to control some of the deadlier insect populations with inorganic pesticides. One of the most famous examples is DDT. Before it was banned for health and environmental reasons, the controversial synthetic pesticide helped eradicate the Aedes aegypti mosquitoes—which transmit yellow fever and now Zika—from most of Latin America during the mid-20th century. It was also used by farmers as an effective method of insect control in crop and livestock production.

But in recent years, biopesticides, either biochemical pesticides (such as insect sex pheromones interfering with mating, or plant-derived products) or microorganisms have emerged as a “green” weapon against pests. The interest is due to several factors.

Consumers anxious about agrochemicals want healthy organic produce grown without synthetic pest control chemicals. Additionally regulatory authorities have been putting more restrictions on the use of synthetic agrochemicals and dedicating more land for organic farming. Lastly, in order to feed our rapidly expanding population, expected to grow from 7.6 billion to 9 billion by 2050, growers need more sustainable agricultural practices.

Although the biopesticide market is growing at a healthy annual rate of 15-20% a year, manufacturers still face significant hurdles in getting their products to market. This is particularly true in Europe, where the European Food Safety Authority and the 28 European Union member states, have their own approaches for interpreting data, despite a common Regulation, and not every member state has the experience and knowledge to deal with biopesticides in a pragmatic way.

For instance, biopesticidal micro-organisms such as Trichoderma harzianum or Bacillus thuringiensis, are common micro-organisms in nature. By looking carefully at their biology, their way of living, and by performing additional safety tests, it can be concluded that they are safe to use as biopesticides. Yet relying on fewer studies than needed for synthetic chemical pesticides, and more on common knowledge, biology and public data is often beyond the comfort zone of the more chemically orientated risk assessors.  

To ease this process, the European Commission established a working group in 2016 and charged it with clearing up the murky waters of evaluating these products. Chaired by the European Commission, the working group is now in the process of developing guidance on how to interpret the data requirements for micro-organisms specifically.

In the meantime, companies must be diligent in preparing their products’ dossiers for regulatory review. They need to be sure that they have a thorough understanding of the biology of the microorganism they are working with, and have an idea about the metabolites it could form with regard to the pesticidal mode of action.

Here are four points to that developers of biopesticides should consider as they navigate the regulatory channels. 

  • Those Meddlesome Metabolites. Any dossier submitted to regulators naturally must include a list of ingredients contained in a biopesticide, including any potentially toxic byproducts that could be harmful to consumers. But while many biopesticides contain metabolites, not every metabolite is toxic enough to keep the product off the shelf. Clarifying how to deal with metabolites is one of the top priorities of the EU working group, which is seeking a more harmonized approach on what questions the EU and member states should be asking regarding metabolites. In the meantime, developers should keep in mind that certain issues regarding metabolites could be more easily addressed for well-characterized microorganisms, such as Trichoderma harzianum, Beauveria bassiana and Bacillus subtilis, when seeking regulatory approval.
  • Do You Really Know Your Microorganism?  It helps if you have some idea how the bug works, and what the toxic mechanism of action is. Too many toxic metabolites, or a potentially pathogenic micro-organism, are a no-go.
  • Be Careful Which Testing Strategy You Use. When compiling data on the safety and effectiveness of your product, consider whether you can build a strong defense for not providing a certain study, or conducting a certain study in a slightly different way. Being proactive can cost less time and money, and reduce the impact on research animals.
  • Choose Your Partners Wisely. Given the considerable investments that will be required as a company decides to move a biopesticide forward, it will be important to choose partners, such as a contract research organization, with a proven track record in agrochemicals. Not only should a partner have a good GLP lab, they must also have extensive experience in agrochemicals. Not every CRO is comfortable performing tests specific for microorganisms.

This is the first in a year-long series, Chemical Attractions, that showcases developments in the agrochemical and industrial chemical fields. Stay tuned for our next installment on management of persistence testing.