New requirements for approval of active substances that are micro-organisms

The European Commission published on 1 September 2022 new requirements for approval of micro-organisms and plant protection products ("PPPs") containing them. These new requirements was adopted by means of a comprehensive legislative package composed of four EU implementing Regulations amending the existing legal framework applicable to PPPs:

• Regulation (EU) 2022/1438, which amends Regulation (EC) No 1107/2009 concerning the placing of plant protection products on the market ("PPPR") and, in particular, its Annex II which lies down the procedure and criteria for the approval of active substances.
• Regulation (EU) 2022/1439, which amends Regulation (EU) No 283/2013 setting out the data requirements for active substances.
• Regulation (EU) 2022/1440, which amends Regulation (EU) No 284/2013 setting out the data requirements for plant protection products.
• Regulation (EU) 2022/1441, which amends Regulation (EU) No 546/2011 setting out the uniform principles for evaluation and authorisation of PPPs.

The four regulations composing this comprehensive legislative package apply as from 21 November 2022 and are part of another step taken by the Commission in order to facilitate and promote the placing on the market of biocontrol means.

New changes to note regarding new active substance data requirements for micro-organisms.
One of the objectives of the new Regulation (EU) 2022/1439, according to Recital (3), is to better delimit the differences between micro-organisms and chemical substances, especially, when it comes to metabolites produced by the micro-organism. In this regard, the new regulation adds an introductory part in Annex to Regulation (EU) No 283/2013, in order to better clarify when application dossiers for approval of active substances must comply with the requirements of Part A (standard requirements), or of Part B thereof (new requirements for micro-organisms). This shall be determined taking into account the properties of the micro-organism, and in particular of the metabolites produced by it.

The purpose of this Part B applicable to micro-organisms is to improve and accelerate their approval at EU level. However, the new changes brought in this respect may not be sufficient to achieve such purpose and, in fact, may instead result in more data requirements to comply with and thus higher costs and difficulties for applicants seeking to introduce biological alternatives on the market. As one example, it is relevant to note Point (x) of Part B of the Annex to Regulation (EU) No 283/2013, which states "all micro-organisms shall be considered as potential sensitisers". This presumption may have relevant implications for companies when it comes to labelling, restrictions of use and other requirements for commercialisation of PPPs.

New changes to note regarding the criteria for categorisation of micro-organisms as low-risk active substances.
Another relevant change is brought by Regulation (EU) 2022/1438, which amends Point 5.2 of Annex II to the PPPR in order to establish more specific criteria for considering micro-organisms as low-risk active substances. In particular, the new wording of Point 5.2 provides that a micro-organism may be considered a low-risk active substance if its susceptibility to at least two classes of antimicrobial agents has been demonstrated. In addition, viruses that are virulent variants of a pathogen with adverse effects on non-target plants cannot be eligible for low-risk status.

The Commission adopted these new requirements in order to offer more clarity and certainty on what elements shall be fulfilled in order to grant the low-risk approval (Recital (11) of Regulation (EU) 2022/1438). However, these new requirements may not solve in practice the issues that applicants currently face when trying to obtain low-risk approvals for their microorganism at EU level.

Currently, there is no homogeneous and consensual approach when deciding whether a micro-organism shall be considered a low-risk active substance. Even if the micro-organism shows sensitivity to antimicrobials (two or more classes) as requested in the above-mentioned Point 5.2, this does not imply "per se" for evaluators that the micro-organism shall be granted low-risk status. In practice, evaluators also take into account other aspects, such as possible production of metabolites of concern or whether risk mitigation measures are necessary. In fact, even general mitigation measures, such us personal protective equipment (necessary for micro-organisms as a general rule) has been considered an element justifying the rejection of the low-risk status.

In this regard, it is important to note that for a micro-organisms to be granted low risk status, Article 22 of PPPR only requires evaluators to conclude that the PPPs containing the micro-organism in question "may be expected" to present a low risk to human and animal health and the environment. In other words, the point on the risk mitigation measures should not be given excessive weight within the EU approval process itself, as it is fully assessed at a letter stage, during the product authorisation process, as required by Article 47 of the PPPR.

Important points that are missing in the new EU Implementing Regulations.
Recital (2) of Regulation (EU) 2022/1439 states that the new data requirements for micro- organisms aim to help the achievement of the objective of the "Farm to Fork" strategy to reduce reliance on chemical PPPs. However, it is not entirely clear whether these new Regulations may successfully achieve this objective in the short/medium-term. Indeed, there are many critical points that are missing in these regulations and are key to facilitate and accelerate placing of biological control alternatives on the market.

Firstly, the new regulations do not provide for reduced timelines in evaluations of micro-organisms or PPPs containing them. Therefore, each Member State will have to decide whether to adopt particular rules to accelerate PPPs authorisation procedures or to grant other benefits to facilitate the placement of biocontrol alternatives. This may generate important differences between national measures in each Member State that, in turn, may lead to less harmonisation and more complexity for applicants when placing product across the EU. 

Secondly, the regulations do not seem to envisage the adoption of guidance documents developing in detail the criteria to be applied by evaluating authorities at EU and Member State level in approval and authorisation procedures.

Thirdly, there is also no provision encouraging and ensuring the constant training of evaluators in order to ensure better and harmonised evaluations by national evaluators. This may result in different criteria applied by Member States in the evaluation of micro-organisms at EU level and the PPPs at national level. As a result, companies will continue to face difficulties in marketing biological alternatives to chemicals, thereby hindering the achievement of the main objectives of the EU Farm-To-Fork Strategy.

On top of the above, it is important to mention the usual issues that applicants generally face during the EU approval process when defending their technical supporting data before all competent authorities involved. Indeed, prior to the adoption of these four regulations, applicants for approval or renewal of active substances usually faced important difficulties in the EU approval process, especially, at a later stage during the peer-review phase, when RMS and EFSA's conclusions are discussed by all Member States.

At this stage, criteria and conclusions are sometimes challenged or modified, once the evaluation has already been conducted. When this happens at this late stage in the process, the applicant has very little room for manoeuvring and. even if it tries to submit new data to rebut these new conclusions, the new information is sometimes disregarded or not duly taken into account by the auhtorities. The new regulations seem not to offer any solution in this regard. The right of defence of the applicant in these situations is still not guaranteed and protected.

Conclusion: there is still work to be done…Are there any alternative options in the meantime?
The purpose of these four new regulations, according to the Commission, is to ensure a "fit-for-purpose" and more flexible risk assessment, which may lead to streamlined application dossiers, shorter  timeframes for accessing the EU market in order to achieve the objectives of the "Farm to Fork" strategy.

According to the Commission, the new rules aim at facilitating the approval of micro-organisms for use as active substances in plant protection products and the authorisation of products containing them. The idea is that farmers should have better access to biological alternatives to chemical pesticides to protect crops in a more sustainable manner.

However, it is not entirely clear whether these new regulations will solve the issues applicants currently face when trying to place biocontrol means on the EU market.

Further changes will need to be made in order to truly achieve an accelerated system for approval of micro-organisms and PPPs containing them so that alternative means of biocontrol may rapidly reach the EU market, in line with the objective of the "Farm to Fork" strategy.

Until then, companies will have to continue assessing and thinking how to use alternative legal paths to place their biocontrol products on the market more easily and rapidly. The existing legal context is a natural regulatory market barrier that may be exploited. A company that knows well the different legal opportunities (existing and forthcoming) in each Member State will be able to implement a registration strategy across the EU that may make a difference with respect to other competitors.