I want to vary my veterinary product to make a change to the product formulation and no technical assessment is required (Item 12)

0.1. Is a technical assessment required for my proposed variation?

Application for a formulation change as a prescribed variation (Item 13A) is only permitted in very limited circumstances. These circumstances are described below (select ‘Item 13A Prescribed Variation’). 

Applications for formulation changes where a technical assessment is not required to satisfy the safety, efficacy and trade criteria can be processed under a non-technical fixed fee variation (Item 12). This includes where the proposed new formulation is closely similar to the existing formulation or where a suitable reference product is nominated. Minor changes to non-active constituents may also be considered as non-technical assessments. Select ‘Item 12’ below to see the full list of circumstances where an Item 12 application is likely to be appropriate.

A technical assessment (Item 14) is required for variations to formulations that include changes:

• to immunobiological products and peptide products
• to active constituents or constituents that act as synergists
• to non-active constituents such as addition, substitution or removal of an excipient (some changes can be made as an Item 12 non-technical assessment—select ‘Item 12’ below to see a full list)
• to ligands
• to ingredients that are subject to scheduling in the Poisons Standard
• where there are concerns about stability
• which affect the permeability and bioavailability of the active constituent in a product (eg solvents and surfactants in topical or injectable formulations)
• that result in a change in drug:excipient ratio of greater than five per cent from the original product formulation

Other formulation changes that require a technical assessment will also be considered as Item 14 applications.

1. Introduction

Variations to non-active constituents in the formulation of non-immunobiological or non-peptide products that may be eligible for submission under Item 12 include formulation changes where:

• the changes to the formulation relate only to non-active constituents, are within the ranges described below, and there is no change to the product specifications
• the proposed new formulation is closely similar (see below) to the approved formulation or
• the formulation has previously been assessed for a nominated reference product which has the same label instructions as the current product.

1.0.1. Closely similar

For a veterinary product formulation to be considered closely similar to another formulation:

• its active constituent/s must be the same and the concentration of its active constituent(s) must be the same as in the reference formulation
• its non-active constituents must be the same or equivalent substances as in the reference formulation and be present at the same or equivalent concentrations (note that minor differences in formulation, specifications, and physicochemical properties may be acceptable if they do not have adverse implications for product quality or biological activity such as efficacy, safety or residues. Where close similarity to a reference product is demonstrated, efficacy, safety or residues data will not be required to demonstrate similarity of the proposed product to the reference product)
• its product specifications (release and expiry limits, and test methods) and physicochemical properties (including pH, particle size and crystal form) must all be the same or equivalent to the specifications for the reference formulation
• its dose form or formulation type must be the same as the reference formulation.

Limits on use (data protection): Where there are limits on use of information on the reference product, written consent from the authorising party is required when access to the information is necessary to determine the application.

Where the reference product does not fully support all risk areas, or the product is subject to limits on use and additional data is being provided to satisfy the safety, efficacy or trade criteria these applications should be lodged as Item 14 applications.

1.0.2. Specific changes to non-actives likely to be eligible for non-technical assessment (Item 12)

For formulation changes under Item 12 (non-technical assessment), product holders are advised to do their own risk assessment and only submit as an Item 12 application if they are satisfied that the formulation does not change the risks already assessed for the product, and that the product will remain within the existing specifications. The types of formulation variations described below will generally be eligible for submission under Item 12:

Antifoam agents—variations in concentration, additions or substitutions for silicone or tallow amine based products present below 0.2 per cent when used as a manufacturing aid.

Antimicrobial preservatives—where a range is listed in the table below for an antimicrobial preservative, increases in the concentration of a preservative within the range listed can generally be assessed under an Item 12. Substitution of an antimicrobial preservative with another listed in the table can also generally be assessed under Item 12, provided the substituted preservative is at the concentration listed, or within the range of concentrations listed. Decreases in the concentration of an antimicrobial preservative while remaining within a listed range may also be acceptable under an Item 12, however suitable scientific argument must be provided to demonstrate that preservative efficacy will be maintained.

Other variations such as additions and/or removals will not generally be considered under Item 12.

Agent	Concentration (%w/v)
Acids and salts
Benzoic acid (sodium benzoate, sodium propionate)	0.1
Sorbic acid	0.2
Alcohol
Benzyl alcohol	1.0
Bronopol	0.01–0.1
Chlorbutol	0.3–0.5
Phenoxyethanol	1.0
Phenylethanol	0.25–0.5
Biguanides
Chlorhexidine salts	0.01–0.1
Hydroxybenzoates
All members of the series and salts (methylparaben, propylparaben, butylparaben)	0.4–0.8 acid
Mercurials
Phenylmercuric salts	0.001–0.002
Thiomersal	0.002–0.01
Phenols
Chlorocresol	0.1
Cresol	0.3
Phenol	0.25–0.5
Quaternary ammonium compounds
Benzalkonium chloride	0.01–0.25
Cetrimide	0.01–0.1

Antioxidants (chemical preservatives)—substitutions within the group of antioxidants tabulated below, provided the variations do not affect the stability of the active constituent in the product, can be assessed as an Item 12 application. Valid scientific argument should be provided to support the change. Substitutions outside the list below are likely to require a technical assessment with stability data under an Item 14.

Alpha tocopherol

Ascorbic acid, sodium ascorbate

Butylated hydroxyanisole

Butylated hydroxytoluene

Sodium metabisulfite

Changes in concentrations of antioxidants will only be accepted under an Item 12 if valid scientific argument is provided demonstrating that the change will not affect product stability. Otherwise, the change will require an Item 14 with stability data.

Binders and disintegrants in tablets or other solid oral dose forms—variations in concentration or substitutions provided the limits for hardness and disintegration and/or dissolution are included in the product specification with appropriate test, and compliance with these specifications is maintained after the formulation change.

Colouring agents and dyes—variations in concentration or substitutions provided the colouring agent is present at one per cent or less in the formulation. The colouring agents should be included on an approved list such as the Food Chemicals Codex, Colour Index (Society of Dyers and Colourists) or the list of food additives contained in the Food Standards Code (Food Standards Australia New Zealand), including all colours listed in Standard A5.

Humectants—variations in concentration do not generally require technical assessment provided that the concentration in the product is less than one per cent.

Inert fillers and carriers—variations in concentration of inert fillers and carriers when used as a manufacturing aid to comply with weights and measures legislation. Variations in concentrations of cereal carriers and substitutions of one cereal carrier for another cereal carrier.

pH adjustors (acids, bases, and buffers)—variations in concentration or substitutions of pH adjustors provided the pH range is included in the product specification, there is no change to the pH range specified in the product specifications, and no changes is expected to the buffering capacity of the formulation during storage.

Solvents—variations in concentration or substitutions within a similar group of solvents for oral formulations do not generally require technical assessment. Changes in solvent concentration/s or substitution in ready-to-use topical formulations, teat dip preparations, intramammary or injectable formulations can have significant effects on efficacy, target animal safety, and residues, and will generally require a technical assessment.

Surfactants; emulsifiers and wetting agents/dispersants—variations in concentration or substitutions within a similar group of surfactants may be assessed under an Item 12 application. This excludes changes in surfactant concentration/s or substitutions in ready-to-use topicals, teat dip preparations, intramammary or injectable formulations where changes to the surfactant are more likely to have adverse effects on the efficacy, target animal safety and residues of the product.

Surfactants; solubilisers in tablets and solid oral dose forms—variations in concentration or substitutions provided limits for disintegration and/or dissolution are included in the product specifications with appropriate tests methods, and compliance with the product specifications for disintegration and/or dissolution is maintained after the formulation change.

Synthetic flavours or natural fragrances—variations in additives, proprietary flavourings and perfumes that comply with a recognised standard, such as the Food Standards Code (Food Standards Australia New Zealand) or the Excluded Stockfood Non-Active Constituents Order (Statutory Rules No. 59, 1995).

Tonicity adjustors in injectables and ophthalmic preparations—variations in concentration or substitutions provided limits for tonicity are included in the product specifications with an appropriate test method, and there is no change to tonicity of the product as a result of the formulation change.

Viscosity adjustors—variations in concentration or substitutions provided limits for viscosity are included in the product specifications with an appropriate test method, and there is no change in viscosity of the product as a result of the formulation change.

2. Legislation

2.1. Framework

The Agricultural and Veterinary Chemicals (Administration) Act 1992 establishes the APVMA as an independent statutory authority of the Commonwealth, responsible for the regulation and control of agvet chemicals in Australia up to the point of retail sale. This Act contains all of the internal details of the establishment of and the functions and powers of the APVMA. It also contains provisions controlling the import and export of chemicals.

The Agricultural and Veterinary Chemicals Act 1994 contains the constitutional and other legal provisions that enable the Agvet Code to have effect.

The Agricultural and Veterinary Chemicals Code Act 1994, among other things, contains the detailed provisions allowing the APVMA to evaluate, approve or register and review active constituents and agricultural and veterinary chemical products (and their associated labels); and to issue permits and to license the manufacture of chemical products. It also contains provisions for controls to regulate the supply of chemical products; and provisions ensuring compliance with, and for the enforcement of, the code.

The Agricultural and Veterinary Chemicals Code Regulations 1995 prescribe detailed provisions of the Agvet Code.

The Agricultural and Veterinary Chemicals Code (Application Requirements) Instrument 2014 sets out the information that must be contained in, or accompany an, application under the Agvet Code.

2.2. Varying relevant particulars and conditions

The APVMA must vary the relevant particulars or conditions if it is satisfied application requirements and statutory criteria have been met (Agvet Code, s 29).

The Agvet Code, s 20(1)(c) defines relevant particulars in relation to the registration of a chemical product as:

• the distinguishing number
• any instructions for the use of the product
• any other particulars prescribed by the regulations.

Other particulars for chemical products prescribed by the regulations are:

(a)  the distinguishing name of the chemical product

(i) the constituents of the chemical product
(ii) the concentration of each constituent of the chemical product
(iii) if possible, the composition and purity of each active constituent of the chemical product
(iv) the formulation type for the chemical product
(v) the net contents for the chemical product
(vi) identifying information for the holder of the registration of the chemical product
(vii) the name of each manufacturer of the chemical product
(viii) the address of each site at which the chemical product is manufactured by the manufacturer
(ix) the date of entry of these particulars in the Register of Chemical Products
(x) identifying information for any nominated agent for the registration.

The Agvet Code defines particulars in relation to approval of a label:

b)

(i) the name of the person who applied for the approval as the holder of the approval
(ii) the name of any nominated agent for the approval
(ii) the name of any nominated agent for the approval
(iii) the distinguishing number
(iv) the instructions and any particulars that are to be contained on the label
(iva) any other particulars prescribed by the regulations
(v) any conditions of the approval imposed by the APVMA.

Other particulars for labels prescribed by the regulations are:

Regulation 17(1)

a) the appropriate signal words required by the current Poisons Standard
b) the name of the chemical product that is to appear on a label for containers of the chemical product
c) the name of each active constituent of the product
d) the proportion of each active constituent of the product
e) the name of each constituent for the product that is

a. not an active constituent; and
b. classified as a poison in the current Poisons Standard

f) the proportion of each constituent referred to in paragraph (e)
g) the net contents of the product
h) particulars determined by the APVMA CEO under sub-regulation (2).

Regulation 17(2)

For paragraph 6(2)(c) of the Act, the APVMA CEO may determine additional particulars to be placed on a label for a product.

Regulation 17(3)

a) identifying information for the holder of the approval
b) identifying information for any nominated agent for the approval
c) the distinguishing name of the chemical product that is prescribed under paragraph 16(a) and entered in the Register
d) the distinguishing number of the chemical product that is entered in the Register.

Conditions are:

a) the conditions prescribed by the regulations (whether or not the conditions are prescribed at the time the constituent, product or label is approved or registered); and
b) any conditions imposed on the approval or registration as the APVMA thinks appropriate.

2.3. Statutory criteria

In addressing the criteria, the applicant may provide information, or valid scientific argument that might address a specific criterion. The following sections of the Agvet Code provide definitions for meeting the criteria:

• Safety (section 5A).

An active constituent or chemical product meets the safety criteria if use of the constituent or product, in accordance with any instructions approved, or to be approved, by the APVMA for the constituent or product or contained in an established standard:

a) is not, or would not be, an undue hazard to the safety of people exposed to it during its handling or people using anything containing its residues; and
b) is not, or would not be, likely to have an effect that is harmful to human beings; and
c) is not, or would not be, likely to have an unintended effect that is harmful to animals, plants or things or to the environment.

To satisfy the s 5A criteria, the APVMA considers chemistry and manufacture, health (including poison scheduling and work health and safety), residues, environment and target safety.

• Efficacy (section 5B)

A chemical product meets the efficacy criteria if use of the product, in accordance with instructions approved, or to be approved, by the APVMA for the product or contained in an established standard, is, or would be, effective according to criteria determined by the APVMA by legislative instrument.

• Trade (section 5C)

A chemical product meets the trade criteria if use of the product, in accordance with instructions approved, or to be approved, by the APVMA or contained in an established standard, does not, or would not, unduly prejudice trade or commerce between Australia and places outside Australia.

• Labelling (section 5D)

In approving a label for a container for chemical products, the APVMA must be satisfied that the label contains adequate instructions. This allows the APVMA to ensure that the risks of using the agvet chemical product are adequately mitigated through appropriate instructions.

The APVMA’s Agricultural Labelling Code and Veterinary Labelling Code also contain further labelling requirements that ensure a standard layout, eligibility and further help in mitigating the risk of using agvet chemical products when used in accordance with the label instructions.

2.4. Application requirements

The Agvet Code, s 8A provides the definition of 'meets the application requirements'.

The Agricultural and Veterinary Chemicals Code (Application Requirements) Instrument 2014, Parts 2 and 4, sets out the information that must be contained in, or accompany an, application under the Agvet Code.

2.5. Applications may be withdrawn

The Agvet Code, s 8D states that at any time after the application is made and before it is determined, the applicant may withdraw it by giving the APVMA written notice of the withdrawal signed by the applicant.

For variations to formulations, the Applications Requirements Instrument requires the submission of formulation information:

(1) The following information is the formulation information in relation to a chemical product:

(a) for each active or other constituent in relation to the chemical product:

(i) the name of the constituent; and
(ii) the CAS number of the constituent; and
(iii) the applicable constituent standard (if any); and
(iv) the concentration of the constituent; and
(v) the purpose of the constituent in the formulation of the product;
(b) the total weight or volume of the product (as applicable);
(c) if the product is a liquid –the specific gravity of the product;
(d) the formulation type of the product;
(e) whether the product contains any ingredients that have a risk of transmitting agents of animal spongiform encephalopathies
(f) whether the product contains any genetically modified organism or any product derived from a genetically modified organism;
(g) whether the product contains any ingredients intentionally engineered to be less than 100 nanometres in one or more dimensions and, if so, those ingredients.

(2) Where this Instrument requires an application to contain, or be accompanied by, formulation information:

(a) the information need not be provided by the applicant (for example, it may be provided by a manufacturer of the product); and
(b) the person providing the information must state the persons, if any, to whom the information may be disclosed; and
(c) the information must be accompanied by a declaration, signed by the person providing the information, that the information is complete and correct.

3. Timeframe and fees

The fee for a non-technical variation (Item 12) is a fixed fee of $2,018. The timeframe is 3 months. Legislative timeframes commence once the application has passed preliminary assessment and fees have been paid.

This application type is subject to an extended assessment period if an Agvet Code s 159 notice is sent requesting additional information or clarification of submitted information. The extended assessment period for a non-technical variation (Item 12) is 5 months.

4. What you need to provide

4.1. Completed online application form

First time applicants will need to complete an online services new user access form to access the APVMA Online Services Portal.

If you are unfamiliar with the application process you may wish to consult the guide to completing an online application.

4.2. The application fee

You may choose to:

• pay the total fee on submission or
• pay the preliminary assessment fee of $902 on submission and the remaining balance once the application has been accepted.

You can choose to pay by credit card, electronic funds transfer or BPAY.

Note: To meet the application requirements you must pay any amount (including an amount in respect of a tax or penalty) that is due and payable by you to the APVMA (including under a law of another jurisdiction or the agvet law).

4.3. Supporting information

The application must contain a summary as to why it does not require technical assessment to satisfy the statutory criteria. In particular, why it does not require technical assessment of risks to residues/trade, workplace health and safety, environment, target safety and efficacy. For example, this may include nomination of a single reference product.

4.4. Information list

It is an application requirement that all applications for approval, registration or variation include a short description of each item of information contained in or accompanying the application – an information list.

Any document (information) submitted with the application constitutes information for the purposes of the information list. This includes supporting information, such as consent for use letters, manufacturer's declarations, MSDS, certificates of analysis, GMP certificates and other such documentation, in addition to the scientific studies or data that may be submitted to specifically address the safety, trade and efficacy criteria.

The online application form contains fields to assist applicants in entering the information required to generate the information list.

Note: Information lists are published, including details of the holders of the information. Applicants should take care not to inadvertently divulge confidential commercial information (CCI) when creating the list.

4.5. Pre-application assistance

Pre-application assistance is available to give applicants advice on the requirements of an application before submission.

4.6. Electronic label (e-label)

The APVMA must have regard to certain matters or details in order to satisfy itself that a label meets the labelling criteria and approve the label (Agvet Code, ss 5D and 14). Applicants must use the e-label template to submit the label details that the APVMA must take into account.

Introduction to preparing a label and the label approval process provides more detailed information.

To meet the application requirements you will need to provide:

• a completed online application form
• the application fee plus any amount that is due to the APVMA
• formulation information
• supporting information
• an information list
• consent for use (if any of the information provided is subject to limits on use)
• an e-label (only required if label changes are necessary).

4.7. Formulation information

The application must contain (or be accompanied by) the proposed new formulation including:

(a) for each active or other constituent in relation to the chemical product:

(i) the name of the constituent; and
(ii) the CAS number of the constituent; and
(iii) the applicable constituent standard (if any); and
(iv) the concentration of the constituent; and
(v) the purpose of the constituent in the formulation of the product;

(b) the total weight or volume of the product (as applicable);
(c) if the product is a liquid—the specific gravity of the product;
(d) the formulation type of the product;
(e) whether the product contains any ingredients that have a risk of transmitting agents of animal spongiform encephalopathies;
(f) whether the product contains any genetically modified organism or any product derived from a genetically modified organism;
(g) whether the product contains any ingredients intentionally engineered to be less than 100 nanometres in one or more dimensions and, if so, those ingredients.

The information can be provided by the applicant, or by a third party. The person providing the information must state to whom the information may be disclosed, and the information must be accompanied by a declaration, signed by the person providing the information, that the information is complete and correct.

Only one new formulation should be submitted per variation application.

An example of when a proposed formulation change would require an updated label is when an excipient that is listed in the Poisons Standard is added or removed and this changes the scheduling of the product. The name and concentration of any excipients in Schedule 5 or Schedule 6 of the Poison Standard also need to be included in the constituent panel on the product label.

5. Examples

5.1. Scenario 1: Variation of a formulation to change the dyes used

5.1.1. Objective

A registrant is seeking to change the dyes used in a synthetic corticosteroid formulation from yellow and green to yellow and blue. The new dyes are found on Schedule 16 of the Australia New Zealand Food Standards Code. The concentration of the active constituent is not changed.

5.1.2. Application type

This application may be considered under a non-technical fixed fee variation (Item 12). The change of dyes is not expected to change the current assessment of safety (section 5A), efficacy (section 5B) and trade (section 5C) criteria.

Risk area	Reason technical assessment is not required
Chemistry	The formulation change is not expected to change the physico-chemical properties of the formulation
Health	Risk to human health is the same as that previously assessed
Poison Scheduling	The product is currently registered and relevant scheduling is established
Residues and trade	Risk to residues and trade is equivalent to that previously assessed
Environment	Risk to environment is equivalent to that previously assessed
Efficacy and Safety	Efficacy and target animal safety is equivalent to that previously assessed
Non-food Trade	Risk is equivalent to that previously assessed
Special Data	Risk is equivalent to that previously assessed

Application type	Timeframe	Extended timeframe	Fee
Item 12	3 months	5 months	$2 018

5.2. Scenario 2: Variation of a formulation based on a registered reference product

5.2.1. Objective

A registrant is seeking to update the formulation of an injectable antibiotic product with that of a reference product. The original registration (an Item 8) was supported by nominating a reference product. This reference product was subsequently varied to amend the formulation. No supporting information has been provided other than the proposed new formulation and nomination of the reference product. Consent has been provided to access limits on use of information relating to the reference product's formulation.

5.2.2. Application type

This application may be considered under a non-technical fixed fee variation (Item 12). The registered reference product shows equivalent risk has already been assessment and the product will continue to meet the safety (section 5A), efficacy (section 5B) and trade (section 5C) criteria.

Risk area	Reason technical assessment is not required
Chemistry	The formulation change has been assessed for the reference product
Health	Risk to human health is the same as that previously assessed
Poison Scheduling	The product is currently registered and relevant scheduling is established. The formulation change does not have any effect on scheduling.
Residues and trade	Risk to residues and trade is equivalent to that of the reference product
Environment	Risk to environment is equivalent to that of the reference product
Efficacy and Safety	Efficacy and target animal safety is equivalent to that assessed for the reference product
Non-food Trade	No change to risk previously assessed
Special Data	No change to risk previously assessed

Application type	Timeframe	Extended timeframe	Fee
Item 12	3 months	5 months	$2 018

5.3. Scenario 3: Variation of a formulation to substitute a carrier of a veterinary feed premix

5.3.1. Objective

A registrant is seeking to substitute one cereal carrier used in a veterinary feed premix formulation for another cereal carrier. The concentration of the active constituent is not changed and the particle size of the proposed carrier will not have an impact on the stability, efficacy or safety of the product. 

5.3.2. Application type

This application may be considered under a non-technical fixed fee variation (Item 12). The substitution of the cereal carrier is not expected to change the current assessment of safety (section 5A), efficacy (section 5B) and trade (section 5C) criteria, as set out in the Agvet Code.

Risk area	Reason technical assessment is not required
Chemistry	The formulation change is not expected to change the physico-chemical properties of the formulation
Health	Risk to human health is the same as that previously assessed
Poison Scheduling	The product is currently registered and relevant scheduling is established
Residues and trade	Risk to residues and trade is equivalent to that previously assessed
Environment	Risk to environment is equivalent to that previously assessed
Efficacy and Safety	Efficacy and animal safety is equivalent to that previously assessed
Non-food Trade	Risk is equivalent to that previously assessed
Special Data	Risk is equivalent to that previously assessed

Application type	Timeframe	Extended timeframe	Fee
Item 12	3 months	5 months	$2 018

6. Start an application

If you want to vary the formulation of your product and a non-technical variation (Item 12) is required:

Start application

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