Veterinary Medicines Regulatory Newsletter, November 2024

1. Veterinary Medicines Directors update: Dr Donald Sibanda and Dr Dharma Purushothaman

Welcome to the November 2024 edition of the Australian Pesticides and Veterinary Medicines Authority’s (APVMA) Veterinary Medicines Regulatory Newsletter. This edition contains information on several regulatory topics, including new product registrations, active approval applications, efficacy and safety, and licencing.

We continue to encourage applicants and holders to participate in the APVMA’s stakeholder meetings, which are conducted from February to October. These meetings are valuable for applicants, industry and the APVMA. Meetings can be used to discuss current and future applications, to raise other applicant priorities, and to provide a forum for other additional concerns. Please contact your case manager if you would like to organise a meeting. If at any time, you require assistance with matters related to the registration and variation of veterinary medicines, please reach out to the Veterinary Medicines Team.

If you have any suggestions or requests for content to be included in future editions of the APVMA’s Veterinary Medicines Regulatory Newsletter, please send these to the APVMA Communications Team.

2. New product registrations

The APVMA publishes a fortnightly Gazette, which includes information about new product registrations and variations to current registered products, particulars, or conditions of registration.

New veterinary product registrations based on a new active constituent which have been published in the Gazette since September 2024 are listed in Table 1.

3. Useful information for industry

In this edition, we have included information for applicants on:

• Agvet Code requests: accessing the information you need
• annual returns
• annual summary of adverse experiences: submitting Periodic Summary Update Reports (PSURs)
• licence variations
• steps of manufacture
• overseas manufacturers
• vet active data requirements and item numbers
• Poisons Standard Schedule 4 entry for animal blood products
• Therapeutic Goods Administration (TGA) ingredient name changes.

3.1. Agricultural and Veterinary Chemicals (Agvet) Code requests: accessing information held by the APVMA

The APVMA has been receiving Agvet Code requests that do not clearly identify the specific information being requested. When submitting an Agvet Code, please provide sufficient information to the APVMA to clearly identify the documents sought, for example, the registered formulation, current product manufacturers or the approved steps of manufacture. Requests that do not clearly identify the information required may encounter processing problems or delays.

Please see our website for further information on Agvet Code requests.

3.2. Annual returns

Each year, to comply with subsection 35(1) of the Agvet Levy Act 1994, holders must report the total amount of product used or sold after being imported into or manufactured in Australia.

Please note that all reporting exemptions have now been removed. All products imported into or manufactured in Australia which are then used or sold must be reported for the previous financial year. Holders should report the quantity of product sold or used in units matching their registered formulation.

Annual returns reporting is available through our online services from 1 July until 30 November each year. Annual returns and levy collection are 2 individual processes. You are required to report product quantity for annual returns, and product dollar value for a levy.

More information on annual returns can be found on the APVMA website.

3.3. Annual summary of adverse experiences: submitting Periodic Summary Update Reports (PSURs)

The Adverse Experience Reporting Program (AERP) would like to remind registration holders to provide the APVMA with their annual summary of adverse experiences, by submitting Periodic Summary Update Reports PSURs if they have not already done so.

The annual summary can be submitted using a variety of formats, but .CSV or spreadsheet files are preferred. Should you require a form to facilitate the submission of a PSUR, please visit the forms page on our website.

If you have any questions relating to this process, please contact the AERP:

Free call: 1800 700 583 (within Australia) – charges apply for calls made from mobile phones.
Email: aerp@apvma.gov.au

3.4. Licence variations

As per subregulation 72A(8) of the Agricultural and Veterinary Chemicals Code Regulations 1995, the Manufacturing Quality and Licensing (MQL) Team will be charging $1,800 for all licence variations which meet the following conditions:

(a) the holder of the licence requests that the APVMA vary the licence

(b) the APVMA determines that a Good Manufacturing Practice (GMP) audit is required to assess the request.

Generally, a GMP audit is required to add a step of manufacture, add a new facility or to remove a condition. The removal of a step of manufacture or secondary facility would not require an audit and therefore does not incur a licence variation fee.

Where a GMP audit is required, the licence variation can be covered during a routine audit or by a separate audit specially for the licence variation. In both instances, the licence variation fee will be payable.

3.5. Steps of Manufacture

Subsection 12(1)(b)(iv) of the Agricultural and Veterinary Chemicals Code (Application Requirements) Instrument 2014 states that it is an application requirement for the steps of manufacture performed at a site to be listed as part of the application. For veterinary chemical products, it is not acceptable to list ‘all steps’ to meet this requirement. Applicants are required to identify each step. Failure to meet this requirement will result in your application being defected at preliminary assessment. There is a list of steps on the application form; however, for your convenience, a copy of the manufacturing steps has also been posted on our website. Please ensure that you choose the right steps from the provided website link. The list of steps of manufacture in your application form should also comply with the manufacturer’s licence for Australian sites, APVMA issued GMP compliance letter or other suitable overseas documentation for overseas sites of manufacture.

3.6. Overseas manufacturers

Following recent enquiries, further clarity is provided on the MQL requirements for manufacturing overseas.

For countries where a Memorandum of Understanding (MOU) or Mutual Recognition Arrangement (MRA) has been signed, the APVMA requires a GMP certificate to show compliance with manufacturing requirements. These countries are:

• The countries that have signed the EC-MRA that was last amended on 1 January 2013: Austria, Belgum, Bulgaria, Cyprus, Czech Republic/Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain and Sweden.
• The countries that have signed the EFTA-MRA: Iceland, Liechtenstein and Norway.
• Northern Ireland and the United Kingdom under the UK-MRA.
• New Zealand under an MOU with the Ministry for Primary Industries.
• Switzerland, US and Canada.
• Laboratories that have a certification of compliance with the ISO/IEC 17025 Standard.
• Certification from laboratories that are in countries that NATA have signed an MOU.

For countries which participate in the Pharmaceutical Inspection Co-operation Scheme (PIC/S), the APVMA requires a GMP certificate and GMP audit report. The list of countries that are members of PIC/S can be found on their website and includes countries like Argentina, Croatia and Indonesia.

Further information on the requirements from the specific countries can be found on our website.

3.7. Veterinary actives: item numbers and data requirements

The APVMA has received enquiries from industry seeking clarification on the overall requirements, module selection and approval of new sources of actives for veterinary products.

3.7.1. Pharmacopeia actives

Existing actives that comply with a current APVMA recognised pharmacopeia monograph (USP, BP or Ph. Eur.) can be submitted as either:

• an item 24 application with a 1.0, 2.5 and 11.3 module
• part of an item 10 application with a 2.5 module to assess the source of active
• part of an item 5 or 6 application without an additional chemistry module or fee.

The APVMA requires 3 certificates of analysis (CoAs) for 3 production scale batches manufactured at the nominated source. A certificate of suitability from the relevant European Pharmacopoeia monograph or standards (CEP) as granted by the European Directorate for the Quality of Medicines (EDQM) should also be provided, if available. Residual solvents and elemental impurities should be tested as part of the specifications unless valid justification is provided.

3.7.2. Actives with no recognised pharmacopeia

Applications for approval of new sources of existing actives which have no recognised pharmacopeia monograph can be submitted:

• as an item 17 (fixed fee and timeframe) application
• as part of an item 10 application with a 2.3 module to assess the source of active.

For new sources of non-pharmacopeia actives, the APVMA requires data in accordance with the APVMA guidelines including:

• identification of the active constituent
• detailed description of the manufacturing process and quality controls
• proposed specifications and justification as to why they were chosen
• batch analysis data for 3 commercial-scale batches manufactured within the last 2 years
• analytical method and validation data
• stability data if there are known stability concerns of the active – for example, diazinon and malathion.

This information is commonly found in the closed part of a drug master file and, if necessary, this information can be provided by the manufacturer directly to the APVMA citing the decision number in an email.

3.7.3. Non-pharmacopeia actives accepted with limited data

In some instances, the APVMA may accept limited data even when the active does not comply with a recognised pharmacopeia. Past examples accepted by the APVMA have included:

• an additional manufacturing site that follows a previously approved manufacturing method with identical specifications
• an active which may be inherently low risk due to being simple molecules of low toxicological significance, for example fatty acids or fatty acid esters
• Metal-EDTA complexes, for example, disodium cobalt EDTA
• an active where there is a related molecule, for example a different salt that has an approved pharmacopeia monograph with appropriate bridging justification
• an active that does not comply with the approved pharmacopeial monograph with justification for the discrepancy.

The APVMA will consider these actives on a case-by-case basis, under an Item 24 with 1.0, 2.4 and 11.3 modules or as part of an Item 10 application with a 2.4 module to assess the source of the active. In these situations, the applicant should consider the data requirements for actives where there is no recognised pharmacopeia and provide appropriate justification where this information is not provided.

3.7.4. Residual solvents, elemental impurities and additional parameters for pharmacopeia actives

The APVMA requires testing of residual solvents (as per VICH GL18 (R2)) and elemental impurities where applicable (as per USP 〈232〉 Elemental Impurities – Limits and ICH Q3D (R2)), even for pharmacopeia actives. Generally, the APVMA considers residual solvents for all actives unless justification is provided.

In general, for a pharmacopeia active, the APVMA records the impurities as ‘comply with the pharmacopeia monograph’ and then lists any additional parameters that are on the certificates of analysis, for example residual solvents, particle size and elemental impurities. If an applicant wishes for specifications on the certificates of analysis to be excluded in the approval, appropriate justification should be provided with the application.

Additional information regarding these processes can be found in the APVMA guidelines and Active constituent application guidance. This information does not address immunobiological actives or new actives which have more specific requirements.

Further information on these actives can be found on our website, or specific advice can be provided under a PAA (pre-application assistance).

3.8. Poisons Standard Schedule 4 entry for animal blood products

In 2023, a proposal was submitted to the Therapeutic Goods Administration (TGA) with the intent to control the access of animal blood products for veterinary use under the Poisons Standard. Animal blood products are not currently captured in the Poisons Standard and have not been previously considered for scheduling. On 22 May 2024, the TGA published their final decision to amend the current Poisons Standard in relation to animal blood products in the ‘Notice of final decisions to amend (or not amend) the current Poisons Standard’, with the decision included as a Schedule 4 new entry.

For more information on this decision and inclusion, please refer to the TGA Notice. Please note that the implementation date for the new scheduling requirements has been revised and will come into effect from 1 February 2025.

3.9. TGA ingredient name changes

In recent years, the TGA has been amending ingredient names and these are now being updated in the Poisons Standard (the Standard for the Uniform Scheduling of Medicines and Poisons, or SUSMP). While there had been a discretionary period in which dual naming was permitted, affected medicines released for supply, with some minor exceptions, are now be required to reflect the new names. Additional information regarding this change can be found at Updating medicine ingredient names - the overview | Therapeutic Goods Administration (TGA).

The APVMA is working to align the naming of agvet chemicals with the Poisons Standard. Under the VLC, the name for a scheduled constituent must be the name specified in the current Poisons Standard. Applicants and holders are encouraged to check and adopt the new ingredient naming requirements for new product registrations and active approvals, where applicable. Applying these changes to existing product registrations, by updating relevant particulars of the label and registration at the next or future variation application is also advised. For existing active approvals, there is no requirement for amendments to naming under a variation application, but holders can contact the APVMA at their discretion should they wish to have the new ingredient name.

Please contact us through enquiries@apvma.gov.au if you have any further questions.

4. Regulatory decision-making and public consultation

4.1. Draft guideline for the evaluation of the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs)

The APVMA has published a draft guideline for the evaluation of the efficacy and safety of non-steroidal anti-inflammatory drugs (NSAIDs) for public consultation. This guideline has been developed as part of our continued efforts to improve efficacy and safety guidance for veterinary medicine registrations. The guideline is aimed at providing clarity on several issues related to efficacy assessments of anti-inflammatories and will aid in consistent decision-making.

We would love to hear your feedback - please see the consultation page on our website for more information. Consultation closes on 20 January 2025.

4.2. Other important APVMA updates

• Our new CEO, Scott Hansen published his first month reflections in September.
• The APVMA 2023–24 Annual Report is now available on our website.

5. New, suspended, or cancelled manufacturer licences

The APVMA’s MQL Team record a list of licences for new manufacturers issued under subsection 123(1) of the Agvet Code and suspended, or cancelled, licences under subsection 127(1) of the Agvet Code. These records are then published in the Gazette.

Table 2 lists new licences issued since July 2024.

You can view the complete list of current licenced Australian manufacturers on our website.

Any questions about these licenses can be directed to the MQL Team.