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#120 Composition/specification of Technical Grade of MPCA/Active Substance

Objective of the study

Microorganisms are produced in vivo or by specific fermentation processes (liquid or solid state). The type of production method and the downstream processing method, will alter the type of Microbial Pest Control Active (MPCA) and determine whether it contains cells, spent fermentation media and/or secondary compounds (metabolites).

Information will be provided in sufficient detail to describe the production process to allow confirmation that the description and specification declared for the MPCA is reasonable. This production process should be kept confidential.

The specification (composition) should be provided with clear information on the representative range of the contents of the MPCA including secondary compounds (metabolites) that are declared to have a defined role in the MPCA.

Circumstances under which the study is recommended to be required

The composition/specification of the MPCA is always required.

Principles about reasoned cases for non-provision of studies

This requirement cannot be waived.

Test organism or substrate

The entire MPCA.

Typical information to be provided by the applicant

One or more study reports should be provided that will be composed of several pieces of information:

  1. Confidential details of the MPCA production (in vivo, or in vitro fermentation) and downstream processes.
  2. The composition of the MPCA, any spent fermentation media and secondary compounds (metabolites), if relevant.
  3. Presence, or lack of, microbial contaminants.

Ref. 1:     The production process will be presented as one or more confidential documents from the production facility that provide details of the standard operating procedures (SOP) and that include information on quality assurance and quality control actions that the producer uses. The information should be provided in sufficient detail for the evaluator to understand the process and to be able to confirm that the quality control procedures are appropriate.

Ref. 2:     In some cases, a MPCA is not available because of a continuous production process or because the MPCA has to be formulated immediately to maintain viability of the microorganism. When a MPCA is available, a study report for the composition will be provided for a 5-batch analysis of the MPCA done by a trusted source and done to a good standard (e.g., an accredited governmental laboratory, ISO or GLP laboratory) to support the information given as a specification.
The composition of the MPCA may be described as a range in the amount of microorganism, in terms of g/kg or g/L (also in % w/w) and cell number (cfu) or biopotency by bioassay. Any spent fermentation media and secondary compounds (metabolites), will be provided if relevant.

For some MPCA the specification is based on biopotency by means of a suitable bioassay. It may help assessors to be aware that due to the complexity of interactions between the host and microorganism, cell and spore counts often have considerable variation and the precision is difficult to standardize. Therefore, it is usually accepted that the specification is given as a range rather than an absolute figure.

If the applicant is at the stage of developing a new MPCA, they may only have small-scale, pilot production. In this case, information from 3-5 batches may be provided and would provide sufficient information for a decision on the specification to be made. However, once production is scaled-up a new 5-batch analysis is usually needed.

The absence of significant secondary compounds (metabolites) can be confirmed from the information provided on the production and downstream process (e.g. if spores are washed there should be no secondary compounds present). If this is not possible, applicants will have to provide details and results of testing, by a suitable method such as HPLC, that confirm if any types and if possible amounts of relevant secondary compounds (metabolites) are present.

Ref 3.    Microorganisms do not per se contain contaminants but the levels of any human pathogens should be minimal. Some applicants may consider providing information on contaminants in the MPCA although it is more commonly presented for the MPCP. Therefore, a study report may be presented on the MPCA, done by a trusted source and done to a good standard (e.g., an accredited governmental laboratory, ISO or GLP laboratory), that provides information on the absence/presence of microbial contaminants. There is no globally accepted level for contaminants, but OECD has developed guidance proposing acceptable levels for human pathogens in products (OECD, 2023). An evaluator may decide to deviate from this standard to some extent if justified.

Typical endpoints of the study

There are no endpoints for the production process.

For the specification, there will be a quantification value or range in terms of g/kg or g/L (also in %w/w) and cell number (colony forming units (CFU), viable cells, Occlusion Bodies (OB)) or biopotency by assay. If relevant, there should be information on any spent fermentation media and presence and amounts of relevant secondary compounds (metabolites).

For microbial contaminants there is no end point value but there would be enumeration values from a study confirming a minimal content of human pathogens.

Testing guidelines

There is no single guideline appropriate for use for MPCA, the applicant will use either one of the guidelines below or a combination.