Impact case study database

(A). Licensing of intellectual property to industry for the development of Metarhizium volatile metabolites as novel fumigants

Certis Europe BV became interested in our research on Metarhizium volatiles in 2016, especially in their ecological role and pesticidal properties. They were particularly interested in the benefits of these volatiles as they were cheaper than current fumigants. Furthermore, Metarhizium volatiles improved operator safety and protected the environment due to their ephemeral, non-phytoxic nature. Our studies [ R5, R6] led to IP that was licensed to Certis Europe BV, who filed two patents (nematicide, molluscicide) of which Prof. Butt was named as the inventor [ C1, C2]. Influenced by our research, Certis Europe BV strategically prioritized the development (investing > GBP250,000) of the fungal biofumigant aspect of their innovative ‘CleanStart’ soil pest management programme.

“Certis Europe has recognized the commercial potential of the Metarhizium volatile compounds and has licensed the IP from Swansea University, as well as filing 2 related patents (for nematicides, molluscicides). From Prof Butt’s research, which has allowed us to accelerate this line of product development, we know that the volatile compounds will repel pests at low dosages and will stimulate plant growth. This potential increase in plant yield using Metarhizium volatile compounds represents a potential ‘game changer’ in the way we manage soil pests and we are committed to obtaining regulatory approval on the basis of this research to license the new products (de novo fumigants). This commitment represents a significant financial investment on our part, and a strategic shift in how we future proof our crop protection solutions. We would not have taken such a decision without the strong underpinning evidence that Prof Butt’s research has uncovered and we look forward to incorporating Metarhizium volatile compounds into our pest management suite to ensure the best crop yields with minimal human and environmental impact.” [Product Development Manager, Certis Europe BV, C1].

Based on our findings [ R5, R6], Certis has developed three new prototype lines based on Metarhizium volatiles: 1. A fumigant that kills plant parasitic nematodes (patent published, WO2019185826A1), which cause annual crop losses exceeding USD100,000,000,000 worldwide; 2. A molluscicide (kills slugs and snails) pellet (patent published, WO2020225149A1); and 3. A repellent granule that prevents attack of crops or stored produce by pests such as slugs, snails, and insects.

(B). Registration and sales of new products based on risk assessment of Metarhizium Secondary Metabolites

The INBIOSOIL [ G2] and BIPESCO [ G3] projects confirmed earlier work (e.g. RAFBCA; G1) that neither M. brunneum nor its metabolites pose any risk to terrestrial and aquatic non-target invertebrates. These findings published in [ R1-R3] were used by industry (Novozymes, Agrifutur) in 2016 to reregister (i.e. updating product dossiers, essentially renewal of the product) M. brunneum for continued sale , specifically strain F52 and the genetically identical BIPESCO 5, sold as Met52 and GranMet respectively [ C8] . Agrifutur’s CEO noted:

“Since 2014 we have been able to establish an R&D product pipeline around Metarhizium brunneum (namely AGF-Ma5) to control new species of pests such as whitefly, aphids and mites. In 2016 we had to renew our dossier. Our researchers have been able to use the new updated dossier which Prof Butt has contributed to, to consolidate our R&D pipeline, which has preserved jobs and created revenue. For example, since 2016 our M. brunneum products have grown in sales by 15 % and we have employed 3 new people” [ C3].

Reregistration allowed distributors of Met52 to continue selling the product and in the case of Fargro, the UK distributor, it has enabled them to focus on new markets for the product, such as the control of the pine weevil, a major forest pest:

“In 2016 when, based in part on Professor Butt’s work in generating risk assessment and efficacy data, and showing that M. brunnuem was non-toxic and non-persistent in the environment, Met52 was successfully reregistered for sale in the EU, Fargro was well positioned to continue to market Met52 as an alternative to the broad-spectrum chemical products which had traditionally been used to control vine weevil, a pernicious pest of fruit and ornamental crops”. [Fargro Technical Director, C4].

(C). Supporting regulatory authorities in reviewing and streamlining the complex registration process for microbial biopesticides

Our research on the secondary metabolites of microbial plant protection agents [ R3] was cited extensively in the 2018 Organisation for Economic Co-operation and Development (OECD) working document on the risk assessment of secondary metabolites of microbial control agents [ C6].

The lead risk assessor for The Netherlands, who is also a risk assessor expert to the OECD biopesticides group, together with Prof Butt, reviewed EU guidelines for risk assessment of metabolites of microbial control agents in 2016, identifying historic mistakes and key areas which slowed down the process (e.g. unrealistic data requirements, unclear guidance on data requirements) and made recommendations to expedite the risk assessment of secondary metabolites [ R4]. Their recommendations were made to industry and regulators. The Dutch expert noted:

“The review was developed with inputs from stakeholders – IBMA and Ctgb (Authorisation of Plant Protection Products and Biocides in The Netherlands). Our suggestions were used by the EU Working Group on Biopesticides in the development of a guidance on metabolites. This guidance was endorsed by the Standing Committee on Plants, Animals, Food and Feed on October 23, 2020 and will apply to applications submitted from 01/11/2021 onwards. Prof Butt has given those who are charged with updating the data requirements for MCAs in the EU tools to evaluate potential production of toxic substances by MCAs, paving the way for quicker registration of microbial pest control agents” [ C5].

Prof Butt has also worked with the International Biocontrol Manufacturers Association (IBMA) which represents ca. 250 biocontrol technology companies worldwide which aim to develop and sell environmentally friendly biopesticides. The Executive Director of IBMA notes that they have cited his research in:

“ advocating with European regulatory authorities to develop a proportionate risk assessment approach regarding the secondary metabolites (as outlined in several of Prof Butt’s research papers) which impacts on the registration of beneficial fungal biocontrol agents…... Prof Butt’s data on fungal metabolites, has provided valuable evidence to present a robust and accurate picture of the current gaps and needs in this area of biofungicide registration and has provided a basis for adaptation of the regulation with a view to increasing product availability to farmers” [ C7].

Furthermore, they note:

”We have also used Prof Butt’s research as the underpinning principle for Platform 1 of our 2019-2024 collaborative roadmap with the International Federation of Organic Agriculture Movements –EU Regional Group, which outlines our position on bringing biocontrol solutions of natural origin to the market via dedicated proportionate regulation” [ C7].