Operational Notice:
Separate Registration of Related Veterinary Medicinal Products

December 2003

Individual Dose Forms

Individual dose forms include tablets, caplets, capsules, implants, sachets, syringes and pipettes packaged and presented for use as a discrete dose for an individual animal. Where there is more than one dosage mass (eg tablet size) of an individual dose form, applications for registration by the APVMA should include numbers and/or words in the product name to indicate the different dosage mass, and each dosage mass will require a separate registration.

This requirement applies even if the different dosage masses are made from the same bulk formulation. For example, if a company formulates a bulk mix containing 1g/kg of active ingredient, then makes it into three different tablet sizes - for example 10mg/tab, 20mg/tab or 50mg/tab - each of the three tablet sizes will require separate registration.

Each of these separate products may have several pack sizes. The pack size will indicate the number of doses in each pack, rather than the dosage mass - for example, 10 or 50 or 100 tablets. Provided they have identical label instructions, different pack sizes will not require different product names, and may be registered as a single product.

Multi/Variable Dose Forms

Multi/variable dose forms include powders, pastes and liquids packaged and presented for use as a bulk pack where discrete doses need to be measured out before administration or application to an individual animal. Where there is more than one concentration of a multi/variable dose form, the product name should incorporate numbers and/or words to indicate the different concentration. Each concentration will require a separate registration.

This requirement applies even if the different concentrations are made from the same bulk formulation. For example, if a company formulates a bulk mix containing 1g/L of active ingredient, then makes it into three different concentrations by adding or instructing the addition of diluent - for example 10mg/mL, 20mg/mL or 50mg/mL - each of the three concentrations will require separate registration.

Each of these separate products may have several pack sizes. The pack size will indicate the weight or volume in each pack, rather than the concentration - for example, 1L or 5L or 10L packs. Provided they have identical label instructions, different pack sizes will not require different product names, and may be registered as a single product.

In the case of products that have an individual dose form, differing dosage mass is analogous to differing concentration of active for multi/variable dose packs, and so separate product registration is required.

Background

It has long been NRA/APVMA policy that related veterinary medicinal products, which have different dosage masses or different concentrations, be registered as separate products. This was also the practice of the individual State regulatory bodies prior to the National Registration Scheme coming into existence.

Although they are considered to be separate products, any applications for additional similar products are considered to be secondary to the primary application (usually the product with the highest dosage mass/concentration). This saving is reflected in the lower evaluation fees for the secondary applications.

The principal reasons for this position are as follows:

Safe and effective use of products

Individual dose products, although often produced from the same bulk formulation, will have different filling/extrusion/pressing steps in the formulation process. This may result in different pharmaceutical properties for the individual products.

The different pharmaceutical properties may result in a different efficacy and safety profile for the individual products. These products sometimes require different label instructions to ensure their safe and effective use.

Individual doses and the packs containing those doses should be easily recognised and differentiated, so that inadvertent over-dosing or under-dosing may be avoided. Distinctive product names are part of a regulation strategy to help prevent errors in dosing. Manufacturers often use different coloured packaging, which also helps product recognition.

Product stability, which may impact on efficacy and safety, may be more critical for individual dose forms than it is for multi/variable dose packs. It has recently been agreed that stability data for any size multi/variable dose pack can generally be used to support registration of any other pack size. This does not apply to small individual doses, such as different tablet masses.

Avoiding confusion between differences in formulation details and different pack sizes/dosage masses/concentrations

As stated above, different dosage mass products (eg different tablet sizes) may have different pharmaceutical properties, and therefore different specifications for the individual products.