Veterinary Manual of Requirements and Guidelines - Vet MORAG

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Category 12 Application

1.   DEFINITION

Schedule 6 of the Agvet Code Regulations describes a Category 12 application as:

Application to vary particulars or conditions of registration or label approval if:

  1. the variation is to allow a minor change; and
  2. no data of a technical nature is required.

A Category 12 application involves variation/s to the product label or product details1 which do not require submission of data for technical assessment. If a label must also be varied as a result of a variation to product details, this will be done as part of that application and a separate application to vary the label will not be required.

1.1.   Application types

The following types of veterinary applications are eligible for assessment under Category 12:

Variation to product label

  • minor variation to the product name, where technical assessment is not required
  • any other variation to the layout (including colour) or wording of the label, other than those eligible for a Category 13 application, or permitted without an application under Permit 6868

  • any other label variation where no data of a technical nature are required.

Variation to product details

  • variation to concentration of, or substitution of non-active constituents as specified in section 4 in this chapter where the product details otherwise remain unchanged and further technical assessment is not required

  • variation to the site of manufacture (site of formulation) of a product2 where the new site is in Australia and licensed by the APVMA for the type of product and steps of manufacture involved, the product details otherwise remain unchanged and further technical assessment is not required
  • reduction of shelf life of a product where the product details remain unchanged and no technical assessment is required

  • additional pack size for the registered product, where product details otherwise remain unchanged and further technical assessment is not required.

2.   REQUIREMENTS

When making a Category 12 application for variation to the registration of a product, applicants must provide:

2.1.   Application form

 

If the application is for a label variation only (except copying of uses of a reference product or additional pack size), applicants should use the specific application form (KP25F06 or KP25F07). There is no requirement to supply formulation details, or an Application Overview in this form.

A separate application form for variation to product details (eg minor formulation variation, additional pack size or variation to site of manufacture), or to copy uses of a reference product, is also available on the APVMA website. This document is a combined Application Form and Overview. It includes formulation details.

2.1.1.  Electronic Application Registration System (EARS) submissions

In May 2007 the APVMA released EARS client software which enables applicants to electronically complete and submit Category 12 applications to the APVMA.

To gain access and use of the EARS software client applicants must complete the EARS user enrolment form.

Once enrolled, applicants are supplied with a username and account and CD with the EARS software client. Account holders are able to use EARS to submit electronic applications over a secure encrypted internet connection.

2.2.   Label

Applicants must provide a label with the Application Form and Overview. The APVMA recommends that the label be in draft form so that it can be amended if necessary, however applicants may choose to submit the marketed product label (MPL).

Applicants may provide the draft label as either:

  • two copies of the text label (TXL) printed on paper; or
  • an e-label on CD. The CD must be attached to the Application Form and Overview and not submitted separately or by email.

The draft label must include all label components ie primary pack, immediate container and leaflet, as relevant.

All parts of the draft label must be in accordance with the latest editions of the:

After the APVMA has assessed the draft label and is satisfied that the label is acceptable, the APVMA will ask the applicant to provide an e-label of the MPL for approval. If the MPL is acceptable and all other matters relevant to the application are acceptable, the APVMA will approve the label and grant the application.

Refer to Label Approval Process in Volume 5 for further information.

2.3.   Fee and timeframe

The fee for a Category 12 application is $875.

The timeframe is three months.

2.3.1. Fee for an identical change to multiple products

If an applicant wishes to apply for changes to the particulars, conditions, or approved label for a product, and if:

  • the application would normally be made under Category 12; and
  • the applicant wishes to make identical changes to multiple products;
  • the applicant should apply for the changes under Category 14. Under Category 14, the APVMA will charge a fee constructed from the screening fee and finalisation fee, which is considerably less expensive than if the applicant makes multiple applications under category 12.

An example is where a registrant applies for approval for change in the site of manufacture for the registrant’s entire range of products.

Full details are set out in Category 14.

2.4.   Data protection

Data are not required for Category 12 applications, therefore a data list is not required.

However, applicants applying under Category 12 to copy uses from an approved label of another product may need to refer to data relied on by the APVMA to register the reference product. The reference product may also have required access to protected data in relation to the active constituent/s or its reference product. Where the applicant is not the authorising party for the data used to approve the active constituents or register the products, the applicant must obtain consent for use from the relevant authorising parties. Applicants can determine whether they are using protected data by checking the product details on the product search facility on the APVMA website.

3.   GUIDELINES

3.1.   Variation to product label where no technical assessment is required

3.1.1.   Minor variation to the product name

Applications for variations to the product name may be made under Category 12 provided they are minor and not for the purpose of creating a new additional product (repack) for marketing purposes. Application for registration of a new additional product must be made under Category 8 (repack), and a new APVMA product number will be allocated for the additional product. Applications which propose variations to the distinguishing features of the product name, and which do not involve variations to the formulation details, should be made under Category 8 (repack).

A variation to the product name under Category 12 will not result in a change to the APVMA product number.

Variations to the product name:

  • must be minor
  • must not change the distinguishing feature (words or numbers) of the name
  • must not affect the meaning or emphasis of any claim or instruction.

Applicants should refer to Volume 5: Labelling for further guidance on product names and prohibited statements.

Examples of Category 12 minor variations to a product name include:

  • removal or addition of a company name (for example as a result of a company name change) that does not affect the distinguishing words or numbers in the product name
  • removal or addition of punctuation marks, letters or words that does not affect the distinguishing words or numbers in the product name.

Example 1: Application is made for a variation to the product name from ‘MG Biagra 50 mg Capsules for Dogs’ to ‘RB Biagra 50 mg Capsules for Dogs’.

This variation to product name would be eligible for assessment under Category 12.

Example 2: Application is made for a variation to the product name from ‘MG Biagra 50 mg Capsules for Dogs’ to ‘MG Biagra 50 mg Capsules’. The target species – dogs – is included in the label claim.

This variation to product name would be eligible for assessment under Category 12.

3.1.2.   Variation to the product label, consistent with an identical or closely similar reference product

Application to vary the product claims and other label instructions or information, where this is consistent with an identical or closely similar reference product, may be made under Category 12 provided that further technical assessment is not required and there are no data protection issues.

For this type of application under Category 12, the technical assessment has already been conducted for an identical or closely similar reference product. See Categories 6, 7 and 8 (image products and repacks) and see Definition of terms used in this manual in Volume 2 for definitions of ‘closely similar’, ‘image products’ and ‘repacks’.

Applicants must provide the name and number of the reference product.

Example 3: Application is made for a variation to the label of an anthelmintic cattle drench product to include an additional use in sheep. Extension of use to sheep has recently been approved for the repack reference product. There are no data protection issues because the applicant has provided a consent-for-use letter from the registrant of the reference product supporting this application to adopt the new use pattern in sheep.

This proposed variation would be eligible for assessment under Category 12.

3.1.3.   Variation to the label layout (including colour) or wording

Applications of this nature are for any other variation to the layout (including colour) or wording of the label, other than those eligible for a Category 13 application, or permitted without application under the current Permit 6868.

Example 4: Application is made for a variation to the product label to include a dosage table on the carton. The currently approved label has the same dosage table on the leaflet only.

This proposed variation would be eligible for assessment under Category 12.

3.2.   Variation to product details where no technical assessment is required

3.2.1.   Variation to concentration of, or substitution of, non-active constituents

Applications of this nature are to vary the concentration of a non-active constituent, or to substitute another non-active constituent, as specified in Minor variations to non-active constituents in section 4 of this chapter, where the product details otherwise remain unchanged and further technical assessment is not required.

This applies to pharmaceutical products only. For immunobiological or peptide products, variations to the concentration of a non-active constituent, or substitution of another non-active constituent, will be assessed under Category 14.

This type of application does not include variations to active constituent/s or variations to constituents that act as synergists or are subject to scheduling in the SUSDP. It only applies to the non-active constituents and the variations listed in Minor variations to non-active constituents.

Applicants must specify the proposed variation/s to the formulation as permitted in Minor variations to non-active constituents.

If the application for variation is approved, the shelf life of the product with the varied formulation will normally remain unchanged. A shorter shelf life may be required where there are concerns about stability as a result of the varied formulation. A shorter shelf life may also be proposed by the applicant in order to address stability concerns.

The applicant must conduct stability trials using samples from a production batch of the product, with the varied formulation, in containers of the same material as the marketed containers to verify the assigned shelf life consistent with validation of Variations under the Australian Codes of Good Manufacturing Practice. Data from these stability trials must be self-assessed by the registrant, and the APVMA must be advised promptly should test results not comply with the approved product specifications. For more information on stability trials, refer to Chemistry and manufacture (stability) guidelines in Volume 4.

Example 5: Application is made to substitute the rice hulls carrier in a direct-fed microbial product for use in pigs with another cereal carrier – wheat middlings.

This proposed minor formulation variation would be eligible for assessment under Category 12.

3.2.2.   Variation to the site of manufacture of a product (APVMA licensed formulator)

This applies only to pharmaceutical products formulated in Australia. For immunobiological or peptide products, variations to the site of manufacture will require application under Category 14. For products which involve overseas sites of manufacture, variations will require application under Category 14.

Applications of this nature are to vary the site of manufacture (or site of formulation) of a product where the new site is in Australia and is licensed by the APVMA for the type of product and steps of manufacture involved and where the product details otherwise remain unchanged and further technical assessment is not required.

An application will not be required where the name of formulator is changed but the site remains unchanged and the licence number remains unchanged. Written advice with evidence that the licence has been updated is all that is required.

If there is change to the licence number, an application will be required.

This type of application does not include changes to the site of manufacture (source) of the active constituent, which will be assessed under item 4.5.8 of Category 14, if such assessment is required. Sites of product manufacture (formulation) include any subcontractors engaged in a step of manufacture including formulating, filling, packaging, labelling, and analysis or testing. Applications may include the following variations:

  • change to a different APVMA-licensed site;
  • addition of another APVMA-licensed site, either for single step or all steps;

  • relocation of an existing APVMA-licensed site.

Where the variation is the result of relocation or where there are any other changes to an existing site (for example, changes in equipment or buildings), the licence holder must have contacted the APVMA so that if necessary, arrangements can be made for an audit and issue of a new licence.

Applicants must clearly specify the proposed variations including which type of variation they are applying for (change/addition/relocation) and the Manufacturers’ Licence number.

Example 6: Application is made for approval of an additional Australian good manufacturing practice (GMP)-licensed formulator (located in Queensland) for a cattle drench product that is currently manufactured by either an overseas formulator or an Australian GMP-licensed formulator (in NSW).

This proposed variation would be eligible for assessment under Category 12.

3.2.3.   Reduction of product shelf life

Applications of this nature are to reduce the shelf life of a product where the product details remain unchanged and no technical assessment is required.

Applicants must clearly specify the proposed variation/s.

Example 7: Application is made to reduce the shelf life of a non-steroidal anti-inflammatory injectable product for use in dogs because the manufacturer has experienced difficulties in meeting approved product expiry specifications as a result of a minor formulation variation.

This proposed variation would be eligible for assessment under Category 12.

3.2.4.   Additional pack size

Applications to approve additional pack sizes may be made under Category 12 provided that further technical assessment is not required.

Applications of this nature are to add a new pack size to a registered product where all other product details (including name, concentration and standard for each ingredient; release and expiry specifications; immediate container specifications; shelf life; and site of product manufacture) are unchanged.

Applicants must provide a copy of the proposed marketed product label, including the additional pack size, for approval.

Note that assessment of stability data will be required if there are changes to the packaging material or closure system of the immediate container. Stability data may also be required for proposed new pack sizes that are smaller or larger than registered pack sizes. If stability data are required, the application will be assessed under Category 14.

Registration of a smaller or larger pack size outside a range of approved pack sizes may occasionally require toxicology and/or OHS assessment. Such applications will be assessed under Category 14.

Example 8: Application is made to add a 2 kg pack size for a product that currently has approved pack sizes of 500 g, 1 kg and 5 kg.

This proposed variation would be eligible for assessment under Category 12.

3.3.   Other variations where data of a technical nature are not required may be made under Category 14

Applications for other minor variations to product details or labels, where technical assessment is not required, other than those variations specified in this chapter (Category 12) or Category 13, or allowed without application under the current Permit 6868, may be made under Category 14 as a non-technical assessment.

Details of variations permitted without an application under Permit 6868 can be found on the Permits website at http://permits.apvma.gov.au/PER6868.PDF.

Applicants must provide details of the proposed product variations in the application overview. Label changes must be highlighted on the submitted labels.

4.   MINOR VARIATIONS TO NON-ACTIVE CONSTITUENTS

This section sets out minor variations to non-active constituents in the formulation of non-immunobiological or non-peptide products3, which may be made under a Category 12 application. Variations to these non-active constituents do not generally require technical assessment provided the parameters in this section are met.

However, if in the opinion of the APVMA the variation proposed is not minor, or the resultant formulation is not closely similar to the original registered formulation, or the product specifications are changed, the application will be assessed under Category 14.

Variations in concentration and substitutions of non-active constituents, which may affect the permeability and bioavailability of the active constituent in a product (eg solvents and surfactants in topical or injectable formulations), are not considered minor and are not eligible for Category 12 application.

Variations in concentration and substitutions of non-active constituents, which result in a change in drug:excipient ratio of >5% from the original product formulation, are not minor and are not eligible for Category 12 application.

Application must be made under Category 14 for all variations that will not be considered under Category 12.

A minor formulation variation will not be considered under Category 12 if it seeks to retrospectively authorise the variation as part of a later application involving a different variation to the product.

Antifoam agents

Variations in concentration, additions or substitutions for silicone or tallow amine based products present below 0.2 per cent do not require technical assessment when used as a manufacturing aid.

Other variations such as additions and/or deletions will not be considered under Category 12.

Antimicrobial preservatives

Variations in in-use concentrations, or substitutions for antimicrobials listed in Table 1 do not require technical assessment, if the change does not affect the efficacy of the preservative system.

Other variations such as additions and/or deletions will not be considered under Category 12.

Table 1:   In-use concentrations of antimicrobial preservatives

Agent Concentration (%w/v)

Acids and salts

Benzoic acid (Sodium Benzoate, Sodium Propionate)

Sorbic acid

 

0.1

0.2

Alcohol

Benzyl alcohol

Bronopol

Chlorbutol

Phenoxyethanol

Phenylethanol

 

1.0

0.01–0.1

0.3–0.5

1.0

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

Thiomersal

 

0.001–0.002

0.002–0.01

Phenols

Chlorocresol

Cresol

Phenol

 

0.1

0.3

0. 25 –0.5

Quaternary ammonium compounds

Benzalkonium chloride

Cetrimide

 

0.01–0.25

0.01–0.1

(Adapted from Table 7, Microbial and physicochemical properties of selected antimicrobial preservatives, The Pharmaceutical Codex p.518)

Antioxidants (chemical preservatives)

Variations in concentration or substitutions within a similar chemical group of antioxidants do not require technical assessment provided the variations do not affect the stability of the active constituent in the product. Table 2 lists the antioxidants considered to be similar for the purpose of a Category 12 application.

Other variations such as additions and/or deletions will not be considered under Category 12.

Table 2:  Antioxidants

Alpha tocopherol
Ascorbic acid, sodium ascorbate
Butylated hydroxyanisole
Butylated hydroxytoluene
Sodium metabisulfite

Binders and disintegrants in tablets or other solid oral dose forms

Variations in concentration or substitutions do not require technical assessment provided the test and limit for hardness, disintegration and dissolution are included in the product specification and these specifications are met.

Other variations such as additions and/or deletions will not be eligible for assessment under Category 12.

Colouring agents, dyes

Variations in concentration or substitutions do not require technical assessment provided the colouring agent is present at 1 per cent or less in the formulation. The colouring agents must be included on an approved list, such as 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.

Other variations such as additions and/or deletions will not be eligible for assessment under Category 12.

NOTE: Category 12 assessment does not apply to intramammary infusions because the Agvet Code Regulations require that a marker dye such as Brilliant Blue be incorporated in approved intramammary antibiotic formulations.

Humectants

Variations in concentration do not require technical assessment provided that the concentration in the product is <1%.

If the concentration of humectant is greater than 1%, and for other variations such as substitutions, additions and/or deletions, variations will not be eligible for assessment under Category 12 because some humectants also act as solvents and preservatives.

Inert fillers and carriers

Minor variations in concentration when used as a manufacturing aid to comply with weights and measures legislation do not require technical assessment, neither do variations in concentration and substitutions of one cereal carrier for another cereal carrier.

Other variations such as variations in concentration of non-cereal carriers, substitutions of cereal for non-cereal carriers or vice versa, additions and/or deletions will not be eligible for assessment under Category 12.

Ligands

Variations in concentration, substitution, additions and/or deletions will not be eligible for assessment under Category 12.

pH adjustors (acids, bases, and buffers)

Variations in concentration or substitutions of pH adjustors do not require technical assessment provided the pH range is included in the product specifications and there is no change to the pH range specified in the product specifications.

Other variations such as additions and/or deletions will not be eligible for assessment under Category 12.

Solvents

Variations in concentration or substitutions within a similar group of solvents for oral formulations do not require technical assessment.

Other variations such as additions and/or deletions will not be eligible for assessment under Category 12.

NOTE: Category 12 does not apply to a change in solvent concentration/s or substitution in ready-to-use topicals, teat dip preparations, intramammary or injectable formulations.

Surfactants - emulsifiers and wetting agents/dispersants

Variations in concentration or substitutions within a similar group of surfactants do not require technical assessment.

Other variations such as additions and/or deletions will not be eligible for assessment under Category 12.

NOTE: Category 12 does not apply to a change in surfactant concentration/s or substitution in ready-to-use topicals, teat dip preparations, intramammary or injectable formulations.

Surfactants - solubilisers in tablets and solid oral dose forms

Variations in concentration or substitutions do not require technical assessment provided the test and limit for disintegration and dissolution are included in the product specifications, and product specifications for disintegration and dissolution are met.

Other variations such as additions and/or deletions will not be eligible for assessment under Category 12.

Synthetic flavours

Colour additives, proprietary flavourings and perfumes must 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).

Variations in concentration or substitutions do not require technical assessment.

Other variations such as additions and/or deletions will not be eligible for assessment under Category 12.

Synthetic or natural fragrances

Colour additives, proprietary flavourings and perfumes must comply with a recognised standard, such as the Food Standards Code (Food Standards Australia New Zealand) or Excluded Stockfood Non-Active Constituents Order (Statutory Rules No. 59, 1995).

Variations in concentration or substitutions do not require technical assessment.

Other variations such as additions and/or deletions will not be eligible for assessment under Category 12.

Tonicity adjustors in injectables and ophthalmic preparations

Variations in concentration or substitutions do not require technical assessment provided the test and limit for tonicity are included in the product specifications, and there is no change to tonicity of the product.

Other variations such as additions and/or deletions will not be eligible for assessment under Category 12.

Viscosity adjustors

Variations in concentration or substitutions do not require technical assessment provided the test and limit for viscosity are included in the product specifications, and there is no change in viscosity of the product.

Other variations such as additions and/or deletions will not be eligible for assessment under Category 12.

FOOTNOTES

  1. Product details include details of the formulation (including names, concentrations and standards for each constituent), release and expiry specifications, manufacturing process, immediate container specifications, shelf life, and site of product manufacture.
  2. Sites of product manufacture include any subcontractors engaged in a step of manufacture including formulating, filling, packaging, labelling and analysis or testing.
  3. Minor formulation variations for immunobiological products are described in Guideline 49: Data requirements and guidelines for variations to immunobiological products.

REVISION HISTORY

Revision Date Description of Revision
1 July 2005 First edition
1 October 2005

Second edition

  • name of document changed
  • paragraph 3.2.2: amended paragraph relating to variations to veterinary active constituents
  • hyperlinks inserted to Labelling Code, SUSDP and FAISD handbook.
1 December 2005
  • paragraph 2.1: added instructions to use ‘application form for variation to product details’ for additional pack sizes
  • paragraph 3.1.1: added clarification that changes to product name which are not minor should be submitted under Category 8.
1 April 2006

Third edition

  • amended title of paragraph 3.1.1
  • paragraph 3.2.2: added clarification that changes involving overseas formulators require application under Category 14
  • amended the title and introductory text of Appendix A and re-numbered it as section 4.
1 July 2007

Fourth edition

  • paragraph 2.2: revised label requirements
  • add new paragraph 2.1.1 re EARS
  • add new paragraph 2.3.1 re an identical change to multiple products
  • paragraph 3.3: edit to state that variations other than those described in the text should be made under Category 14
  • paragraph 4: edit to state that Category 12 cannot be used to retrospectively legitimise previous product variations
  • paragraph 4: edit to better define ‘minor variation’ to non-active constituents
  • minor text edits.