REGULATORY NEWS

Metabolites of Microbial Biocontrol Agents (MBCAs) – Guidance on risk assessment published

Date: 15 December 2020

For more than 2 decades the definition, handling, and risk assessment of metabolites of MBCAs – also referred as ’relevant metabolites’ or ‘secondary metabolites’ – is a very controversial subject. Core issues are the unsuited, non-factual definitions and the resulting non-fitting data requirements for microbial metabolites (for more information on this topic please refer for example to Scheepmaker et al. 2019 or Huber et al. 2020 (SCC Current News of 26 August 2020).

Now, European Commission published its guidance working document on the risk assessment of metabolites produced by microorganisms used as plant protection active substances (SANCO/2020/12258). This guidance document ‘addresses metabolites present in the active substance and the plant protection product and also those produced by the microorganism after application (in situ production)’.
Fortunately, for the first time the Commission working document acknowledges that ‘chemical and microbial metabolites are equivalent in name only. Therefore, data requirements concerning metabolites of chemical plant protection products would not be applicable to microbial plant protection products’. Unfortunately, the procedure outlined for risk assessment in the guidance document is based on a strong regulatory but still less scientifically oriented approach. Major aim is to determine whether the microorganism is producing a metabolite of concern, defined as ‘a metabolite produced by the strain under assessment, with known toxicity or antimicrobial activity for which an acceptable risk shall be demonstrated via a quantitative risk assessment’. A stepwise procedure is foreseen:

  • Stage 1: Determining the assessment type
  • Stage 2: Collecting a basic set of information on metabolites, resulting in a list of metabolites of potential concern
  • Stage 3: Determining which of the identified metabolites are of concern, resulting in a list of metabolites of concern
  • Stage 4: The risk assessment for metabolites of concern.

On the one hand, the guidance fortunately already includes some scientifically based justifications for waiving of respective risk assessments as for example in the case of viruses for which no further assessment is needed as ‘according to the current scientific knowledge no indication exists that viruses produce metabolites of potential concern’. On the other hand there are several points on which the guidance is less helpful. For example, the natural occurrence and exposure is only partially considered and besides genome sequence data, i.e. proof of absence of genes involved in biosynthesis of a metabolite is the only criterion to exclude a respective stepwise risk assessment. Partially this is attributed to a lack of available scientific data and thus the guidance highlights – or admits - that ‘the present guidance document may be further developed to comply with evolution of science and increasing experience of the EU risk assessors and managers. Firstly, knowledge of microorganisms and microbial metabolites is expected to develop, resulting in the need to reflect such evolution in this document. New scientific and technical approaches supporting the risk assessment of metabolites would need to be incorporated. Moreover, the actual use of microbial plant protection products, and the number of applications concerning microbial active substances are increasing the experience of the EU risk assessors and managers which may trigger a revision of the guidance document’.

The present working document has been finalised in the Standing Committee on Plants, Animals, Food and Feed on 23/10/2020. It will apply to applications submitted from 01/11/2021 onwards.

References

Scheepmaker, J.W.A.,Busschers, M.,Sundh, I., Eilenberg, J. & T.M. Butt (2019): Sense and non-sense of the secondary metabolites data requirements in the EU for beneficial microbial control agents.- Biological Control 136: 1-10.

Huber, L., Lorenz, C. & H. Strasser (2020): Data requirements for biopesticides in EU – problems and needs.- Agrow IHS Markit, Biologicals 2020: 32-34.