Worldwide development of a biopesticide: where to start?

As a GEP and GLP service provider and a regulatory affairs consultant, the international French group Staphyt has been working for over 15 years with companies aiming to put on the market new biocontrol products. This market is currently growing in multiple areas of the world. When it comes to getting a fast return of investments on a R&D budget over 1 million €, it is essential to consider all available opportunities. Europe is known as a challenging region in terms of outcome from the evaluation and the uncertainty on the registration but also in terms of go to market time. Other regions of the world are much more appealing in these aspects to the industry, Brazil and USA among others.

Differences in understanding always lead to misleading advice.

″Biopesticide″ and ″biocontrol″ terms may be two words with definitions commonly agreed.  ″Biopesticide″ is defined as pesticides made from natural substances whereas ″biocontrol″ refers to protection technologies originated from nature, intended to use natural mechanisms to protect plants. Both terms have a common base: biopesticides grouping the 3 main categories of products (such as natural substances, microbials and semiochemicals) and biocontrol including in addition the macrobials (invertebrate agents) as fourth protection technology.

However, beyond this first consensus, regional differences exist, particularly in regulatory processes or in the details of what falls within the scope of biopesticides and biocontrol. For example, the Plant Incorporated Protectants (PIPs) in the USA or the use of genetically modified organisms in Brazil will not enter into the European definition of biocontrol.

How can we get to the market in 2 years in Brazil and the USA and need 7 years for Europe? 

By analysing the regulations that coordinate the registrations of biopesticide in these various regions, each of them has its own specificities with, as a result, notable differences in evaluations: 

1/ In the USA, only the EPA is evaluating. 

2/ In Brazil, 3 ministries or agencies are distributing the work: 

• certification and efficacy at the Ministry of Agriculture (MAPA); 

• toxicology at the Ministry of Health / National Health Surveillance Agency (ANVISA); 

• environmental fate and ecotoxicology at the Ministry of Environment / Brazilian Institute for the Environment and Renewable Natural Resources (IBAMA). 

3/ In Europe, the evaluation process is collegial, involving several actors:

• 1 Rapporteur Member State (RMS), assessing the notifier dossier and preparing the Assessment Report that will be distributed to the other following European actors; 

• 26 other member states will give their point of view;

• EFSA (the European Food Safety Agency) will build the conclusions of evaluation;

• the European Commission will give the final decision. 

To a general extent, the highest truth in a registration dossier lies in the data that will have to be generated in order (1) to identify the (eco)toxicological profile, (2) to populate the risk assessment and (3) to demonstrate the efficacy. 

The set of the data package depends obviously on the nature of the item (microbial, extract of microbial, botanical extract, semiochemical, etc.).

About the studies monitoring, one point differs from the 3 zones: 

• Europe requires studies run under OECD guidelines (even if they accept or request OPPTS-based studies for microbials for instance); 

• In the USA, the rule is to follow OPPTS guidelines; 

• In Brazil, both OECD and OPPTS are accepted along with ABNT guidelines. 

A specific point in the USA to be highlighted is the absence of regulatory demonstration of the innovation’s efficacy; it leads to a significant difference of budget and a much larger possibility of uses to cover on the same crop.

Still, the data packages requested in the various zones are not sufficiently distinct to explain the distance in the time to market. Thus, the processes of registration must be investigated to have the beginning of clarification: 

- In Brazil and in the USA, biochemicals are registered with both active ingredient and formulated product assessed at the same time. This leads to a registration process of 2-3 years. 

- In Europe, the process is sequential: first the active substance has to be assessed for registration before the product enters into the evaluation process for authorization. If the product developed contains a substance already approved, then the timing is about 1-2 years to generate data and 1-2 years of evaluation. However, as soon as the substance is new, the specific step of the substance approval jeopardises the timing (5 years at least to get a substance approved) before having the product authorised.

Organizing a global launch

With a little perspective, it seems that (1) starting to reach for the registration in Brazil and/or in the USA and (2) then considering the profitability of a registration in Europe may look like the finest strategy.

However, details from these different procedures (EU, USA or Brazil) lead to consider the development in parallel rather than sequential. Occurring at the early stage in each of these procedures, they must be considered very much upfront. For example, advantageous fees discount can be obtained in the USA if the notifier company is recognized as small and not operating yet in pesticides. As well, getting a biochemical classification by the Biochemical Classification Committee is also an important step to get a reduced data package. On the other hand, in the frame of the European Transparency Regulation, studies expected to be used for the approval of a substance have to be notified to the Authorities; more particularly studies on vertebrates have to be justified. The notification process is now a prerequisite to avoid any risk of rejection.  

Various details have to be considered in a global strategy; these are small steps with large consequences. 

In the end, to summarise, here are some key points to keep in mind. 

Once the data gap analysis is done, covering all the targeted regions of the world, it is important to identify the same studies requested in the various regulations (acute toxicity on algae for example) and try to build a study plan that will be acceptable under OECD and OPPTS requirements (the two main organisational guidelines to follow). This will help clearly to reduce doubling data and will decrease the development cost. Currently, there is no possibility to get a mutual recognition of registration of active ingredient or formulated product between global regions. At least, it can be tried to have only one data package that fits for all situations.

The second point to address absolutely is to consider the preliminary steps of all regions upfront. Regardless of the priorities of registrations that are expected, covering all the preliminary steps will be a way to make sure that, in due time, there will be no unnecessary hurdles on the way of the registration. 

More information, visit our website: staphyt.com or contact us contact@staphyt.com

Contacts: Héloise Stephan (hstephan@staphyt.com), Geoffroy MOULIN (gmoulin@staphyt.com)

This article is published in AgroPages' Annual business publication - <2024 CROs & CRAOs Manual>.

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We're welcome you to reach us for valuable comments or questions at Elsa Wan (elsa@agropages.com)

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