Dr Yasser Sokeirik

Veterinary chemical products can undergo physical, chemical and microbiological changes on storage. The rate at which these changes can occur depends on the nature of the active constituent(s), the formulation composition, the formulation type, the packaging and, most notably, the storage conditions (temperature, light and humidity).

Agvet Code states that “A person must not supply, or cause or permit to be supplied, a date-controlled chemical product in a container that does not have attached to it an approved label containing: … the expiry date required to be contained on the label as a condition of the registration of the product”. Veterinary chemical products are considered date controlled; therefore, a suitable shelf life should be proposed based on the stability of the product in an Australian climate.

The stability of a veterinary chemical product may be defined as the capability of a particular formulation, in a specific container/closure system, to remain within acceptable physical, chemical and microbiological specifications. Thus, the purpose of stability testing is to provide evidence on how the quality of a veterinary chemical product, in its proposed marketing packaging, varies with time under the influence of a variety of environmental factors, such as temperature, humidity and light, and enables recommended storage conditions and shelf lives to be established.

The APVMA has described the label storage instructions which are relevant to the Australian climate conditions. Accordingly, the APVMA recommends the storage conditions; namely, the temperature and the relative humidity that should be tested in the stability tests. Please note that Australia has climatic conditions encompassing VICH zones I to IV where room temperature is 30°C. In addition, the APVMA has advised to follow the relevant VICH guidelines on stability trial design and testing protocols.

important elements that should be considered in the stability trial of veterinary medicine products:

  • Formulation composition including the description of the product including the formulation composition
  • Batch selection:
    • Minimum of three (at least two being pilot- or production-scale)
    • Should be of the proposed formulation composition
  • The Shelf (Expiry) life specifications are set to be within ±10% of the label claim at expiry
  • Containers
    • As proposed for the marketing of the final product (sizes, composition and closure)
    • Smaller containers of the same material may be used where the smallest commercial size is impractical for study purposes
    • Inverted/side storage to assess the stability of the product if inverted.
  • Test parameters
    • Should include all relevant product release and expiry test parameters specified in the product specifications
    • All test methods with their validation data should be reported
    • Test results should be presented in tabular format for ease of analysis
    • All test parameter results should comply with the expiry limits
  • Statistical analysis should be conducted to confirm the following:
    • All test parameter results should comply with the expiry limits
    • Trend analysis should be conducted to ensure that batches released at or near the lower release limit/s will comply at expiry
    • Outliners and/or out-of-specification results should be appropriately justified.

Australia is in climatic Zones II-IV (VICH). The proposed test conditions should reflect the expected storage conditions as per the Australian climate. the APVMA has advised the following test conditions for each relevant storage label instruction.

Table 1: Product label storage instructions and temperature and humidity design for stability tests
Storage instruction on the product label Real-time stability test protocol Accelerated stability test protocol
Store below –18 ºC (Deep freeze) –20 °C ± 5 °C Not appropriate
Store below –5 ºC (Freeze) –20 °C to –5 °C ± 5 °C Not appropriate
Store between 2 ºC and 8 ºC (Refrigerate. Do not freeze) 5 °C ± 3 °C 25 °C ± 2°C/60% RH ± 5% RH
Store below 8 ºC (Refrigerate) 5 °C ± 3 °C 25 °C ± 2 °C/60% RH ± 5% RH
Store below 25 ºC (Air conditioning) 25 °C ± 2 °C/60% RH ± 5% RH 40 °C ± 2 °C/75% RH ± 5% RH
Store below 30 ºC (Room temperature) 30 °C ± 2 °C/65% RH ± 5% RH 40 °C ± 2 °C/75% RH ± 5% RH

If the submitted data do not cover the proposed re-test period or less than 3 production batches were submitted, a commitment should be made to continue these studies through the proposed re–test period and to place additional production batches. However, the minimum time period covered by data at submission by real time stability test and accelerated stability test should be at least 1 year and 6 months, respectively. 

Stability data after the first opening of the container for parenteral and other sterile products in multi-dose containers should be provided to the APVMA to allow it to assess the in-use stability of the product/packaging. Alternatively, a label statement that instructs the user to discard any unused product within 24 hours of first broaching the container or in the case of eye and ear preparations four weeks after first opening the container should be considered.

The establishment of the shelf life for veterinary chemical products depends largely on the type of trials performed and on the duration of each study. If single study -either real time or accelerated- were conducted, the shelf life will be equal to the duration of the stability trials. If a combination of the two types of study were conducted, an extrapolation technique can be used to extend the shelf life beyond the duration of the trials. The proposed shelf life could be extended to double the real time trial with maximum of 12 month.  

A shelf life can be approved for certain product types under certain circumstances without stability data being provided. The product types include vitamins, minerals, therapeutic pet food, herbal and marine-derived complementary animal health product and other low risk products.