Stability at elevated temperature Aim

To ensure that the properties of formulations are not adversely affected by storage at high temperature, and to assess their long-term storage stability at more moderate temperature, with respect to content of active ingredient (and a possible consequent increase in relevant impurities) and certain physical properties.

Applicability

Specifications for all formulations.

Method

MT 46.3 Accelerated storage procedure.

Note: MT 46.3 is not intended for testing microbial pesticides, which may require conditions according to the product.

Requirements

After storage at 54 ± 2ºC for 14 days, the formulation must continue to comply with the requirements of appropriate clauses for content of active ingredient, relevant impurities, particulate and dispersion clauses.

The average active ingredient content should not decline to less than 95% of the average content measured prior to the test, and relevant physical properties should not change to an extent that might adversely affect the application and/or safety.

Where the formulation is not suitable nor intended for use in hot climates and is adversely affected by very high temperature, the test conditions may be modified. Avoidance of temperatures exceeding 50ºC is likely to be necessary where the formulation is packed in water soluble bags and this may also be necessary in the case of certain household insecticides, such as aerosols (AE).

Alternative conditions are: 4 weeks at 50 ± 2ºC, 6 weeks at 45 ± 2ºC; 8 weeks at 40 ± 2ºC, 12 weeks at 35 ± 2ºC or 18 weeks at 30 ± 2ºC.

Comments

Samples of the formulation taken before and after the MT 46.3 test should be analyzed concurrently, after the test, in order to reduce the analytical error.

Further information must be provided if the degradation of the active ingredient exceeds 5% or a physical property is adversely affected. For example, the degradation products must be identified and quantified. In formulations with concentrations of 1% or below, there may be analytical challenges in identifying the degradation products that may only be at 0.05% level. In such cases available evidence and scientific argument on the likely degradation products should be provided.

Formulation labels must be marked with the release date (month and

4. Aims, applicability, and requirements of clauses, continued

date from which the supplier guarantees the quality of the formulation.

The term "release date" should be used rather than "formulation date", which may lead to confusion between supplier and buyer (see also FAO Guidelines on Good Labelling Practice, revised, 1995).

Formulations are generally expected to continue to be satisfactory in use after storage for at least 2 years from the release date in the unopened original containers, provided that these have been stored according to the instructions given on the label. Information on the storage stability of the formulation must be provided on the label if the intended shelf-life is less than 2 years.

FAO and WHO do not generally recommend storage of formulations for more than 2 years and the specifications are not intended to apply to longer periods of storage. Where a formulation has been subjected to prolonged storage or adverse conditions during storage, analysis and testing are recommended to assess its suitability for use.

For certain products, e.g. LN (long-lasting insecticidal nets), longer shelf-life may be needed. The claimed longer shelf-life must be substantiated with data that demonstrate that the product remains within specification for the longer period.

The rate at which products undergo chemical and/or physical changes depends on the nature of the active ingredient(s), the formulation, the packaging, and the storage conditions. The product remains fit for use as long as the changes do not adversely effect the application, the biological performance, or the safety of operators, consumers or environment. However, such adverse effects cannot be assessed routinely by the buyer and the test of storage at elevated temperature provides an economic means for demonstrating that they should not occur if the product is stored according to the label recommendations.

Reaction kinetics (Årrhenius equation) are not linear with respect to temperature and therefore storage at constant temperature t°C is not equal to storage at variable temperatures with an arithmetic mean of t°C. Estimation of average air/surface temperatures is problematic, even where accurate measurements of daily maxima and minima are available. In addition, the main bulk of a product is not usually subjected to the extremes of temperature reached by the packaging.

Therefore calculation of the impact of a particular storage regime on the stability of a product may be misleading. The recommended test of storage stability is expected to provide a more reliable indicator.

The clause for stability at elevated temperature provides limits for the active ingredient content and physical properties of the product. It is generally accepted that deviations of ±10% of the nominal active ingredient content¹ do not significantly influence the biological performance. Where the active ingredient is unavoidably subject to degradation during recommended storage, an overage ≤10% of the

1 This is not to be confused with the standard tolerances given in the table in section 4.3.2, which do not include an allowance for degradation or overage.

4. Aims, applicability, and requirements of clauses, continued

nominal content may be applied to compensate for degradation.

Alternatively, a limit <95% for active ingredient content after the storage stability test may be proposed. In either case, the manufacturer will normally be asked to provide supporting evidence for the requirement.

A more detailed consideration of shelf life and storage stability matters is given in CropLife International Technical Monograph No. 17,

―Guidelines for Specifying the Shelf Life of Plant Protection Products (‡

June, 2009)¹. See also the FAO International Code of Conduct on the Distribution and Use of Pesticides².

1 Obtainable through the CropLife International website http://www.croplife.org.

2 Accessible through the FAO website.

http://www.fao.org/agriculture/crops/core-themes/theme/pests/pm/code/en/

5. SPECIFICATION GUIDELINES FOR TECHNICAL MATERIALS AND