Veterinary Medicines Regulatory Newsletter, August 2024

1. Directors update: Dr Donald Sibanda and Dr Mariette van den Berg

Welcome to the August 2024 edition of the Australian Pesticides and Veterinary Medicines Authority’s (APVMA) Veterinary Medicines Regulatory Newsletter. This edition includes information on several regulatory topics, including updates on the APVMA’s chemical reviews and cost recovery activities. We have also included valuable information for industry, including active application types and requirements, application data transfers, and GMP audit review timeframes.

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 May 2024 are listed in Table 1.

3. APVMA to review fees and levies

The APVMA is funded by fees, charges and levies imposed on the industries we regulate and, like all cost-recovery agencies, we periodically review these payments to ensure they reflect current operational costs.

We are currently reviewing our fees, charges, and levies to make sure the right structures are in place to effectively regulate and meet legislative requirements and community and industry expectations.

The APVMA has a long-standing practice of consultation in relation to proposed changes to these cost-recovery mechanisms. We want to hear from regulated industries and members of the public to understand what any change will mean for industry stakeholders and the community.

On 16 May 2024 we commenced consultation with key stakeholders, and formal consultation is expected to commence in the second half of 2024. We will keep our website updated as consultation progresses.

4. Useful information for industry

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

• guidance on obtaining harmonised veterinary medicine labels in Australia and New Zealand
• data submissions
• limits on use of information
• the Poisons Standard Schedule 4 entry for animal blood products
• TGA ingredient name changes
• Manufacturing Quality and Licensing (MQL): temporary extension to audit review timeframes
• veterinary actives: item numbers and data requirements.

4.1. Guidance on obtaining harmonised veterinary medicine labels in Australia and New Zealand

The New Zealand Ministry for Primary Industries (MPI) Agricultural Compounds and Veterinary Medicines (ACVM) and the APVMA allow harmonised labels for veterinary medicines registered in both countries. Registrants of veterinary medicine products registered in both New Zealand and Australia can benefit from one common label to sell and market in both countries.

Guidance has been issued to clarify the harmonised labelling requirements for industry.

4.2. Status of veterinary mRNA vaccines in Australia

The APVMA is actively engaging with industry, researchers, state and territory governments and our global regulatory counterparts regarding Australia’s regulatory approach to mRNA vaccines for use in animals. There are currently no mRNA vaccines approved by the APVMA for use in animals in Australia.

More information is our website.

4.3. Objective Connect for data submissions

The Veterinary Medicines Team has recently started using Objective Connect to assist with applicant data submissions. A specific benefit of Objective Connect is that it allows for the secure transfer of data files, folders and zipped folders. The zipped folder aspect is particularly useful, as the original folder structure is maintained which assists in the transfer of large data packages, such as international data dossiers.

Access to Objective Connect is also available to External Scientific Reviewers (ESR) and other stakeholders who need to submit data to the APVMA. Once a stakeholder has created a log in with Objective Connect, they can receive an invitation to a specific workplace allocated to an individual application or project. They can easily share large data packages, and work across different workspaces at the same time if working on multiple applications or projects simultaneously.

For further information or assistance providing data using Objective Connect for veterinary products, please contact VetAdmin@apvma.gov.au. Alternatively, you can contact your existing Case Manager on casemanagement@apvma.gov.au.

4.4. Extension of data list trial

Feedback from a range of veterinary product stakeholders has reinforced that applicant access to data lists prior to finalisation is helpful in identifying Confidential Commercial Information (CCI) and in reducing confusion about data item submissions. Considering this feedback, the Veterinary Medicines Administration Team will continue to provide a copy of the data list when the respective application has passed Preliminary Assessment. This means that the pre-existing data list trial will be extended until October 2024.

Applicants are encouraged to provide feedback to VetAdmin@apvma.gov.au on this process to determine its longer-term implementation.

4.5. Proposed product labels – Veterinary Labelling Code compliance

Reference products are nominated for a range of applications submitted to the APVMA. In some cases, a reference product may have a label which does not conform to the current Veterinary Labelling Code (VLC). When relying on a reference product to support a new application, please ensure that you review your proposed product label and take into consideration the current VLC requirements. It is the responsibility of the applicant, to ensure that the proposed product label aligns with the current VLC. Submitting a label which does not comply with the current VLC requirements may result in processing delays due to additional label updates required by the APVMA.

4.6. Reference product data – limits on use of information

The APVMA can use information from any source for the purpose of performing its functions or exercising its powers under the Agvet Code and the Agvet Code Regulations. However, this is subject to certain limitations on use and confidential commercial information provisions contained in the Agvet Code and the Agvet Code Regulations.

Reference products are usually nominated for a range of applications submitted to the APVMA and some of those have limits on use of information (LOUI). The LOUI status of a reference product can be found on the APVMA’s Public Chemical Registration Information System Search (PubCRIS) database.

A reference product that has LOUI should be identified in Section 7 (Access to Information with a Limitation of use Period) of the application form. Relevant consent to access and use this information must also be submitted along with the related application. Applications that cite a reference product, but do not contain the relevant information in Section 7 and related consent documentation will not pass Preliminary Assessment, resulting in additional delays in application processing.

A reference product without LOUI does not need to be listed under Section 7. In these cases, Section 7 can be left blank.

Additional information about accessing information for reference products including LOUI can be found on our website.

4.7. 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. The implementation date for the new scheduling requirements is 1 October 2024.

4.8. 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.

4.9. Manufacturing Quality and Licensing: temporary extension to audit review timeframes

The Manufacturing Quality and Licensing (MQL) Team are temporarily extending the timeframe for completing audit reviews. From 1 August 2024 to 30 June 2025, the MQL Team will aim to complete 90% of audits within 4 months of receipt of information. This time extension will allow the MQL team to focus on key areas including training new staff members and reviewing the new Good Manufacturing Practice (GMP) Audit procedure and Australian Code of Good Manufacturing Practice for Veterinary Chemical Products.

The MQL Team understands that some audits may need to be prioritised during this time. Any priority requests should be directed to the Assistant Director of MQL on mls@apvma.gov.au for consideration where capacity allows.

From 1 July 2025, MQL will then return to the completion target of 90% of audits within 3 months.

4.10. 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.

4.10.1. 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.

4.10.2. 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.

4.10.3. 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).

4.11. APVMA clarifies the recalls process for agvet chemicals

Recalls of an agvet chemical product may be initiated to mitigate potential risks to safety (such as incorrect labelling or packaging failures), concerns that the product may not work as intended, or because of a potential risk to trade. This can be undertaken as a voluntary recall, where a supplier voluntarily recalls a product from the market. Alternatively, the APVMA can compel a supplier to recall the product, known as a compulsory recall.

The APVMA has clarified the recalls process especially the product holder’s role in the recall process.

5. Regulatory decision-making and public consultation

5.1. Chemical Review update

The APVMA continues to progress the reconsiderations subject to the Ministerial Direction on Chemical Reviews issued by the former Minister for Agriculture, Fisheries and Forestry, Senator the Hon. Murray Watt, in July 2023.

Veterinary chemicals included in the Ministerial Direction contain the active constituents neomycin, diazinon and fipronil. The APVMA has published proposed regulatory decisions for neomycin and diazinon, and we are currently considering the submissions received during the public consultation periods.

Chemical reconsiderations include a statutory 3–month consultation period following publication of the proposed regulatory decision.  All stakeholders have the opportunity to provide information or comment on the proposed regulatory decision. However, the APVMA is only able to consider information that is relevant to the statutory criteria of safety, efficacy and trade, which may include scientific studies, or questions relevant to the assumptions used in the APVMA’s risk assessments.

The final regulatory decision on the reconsideration of diazinon is due to be published on 10 September 2024 and neomycin on 18 October 2024.

The proposed regulatory decision for the reconsideration of fipronil veterinary products is scheduled to be published on 29 April 2025, with the final regulatory decision due to be published on 20 October 2025.

If the APVMA’s final decision is to cancel a product’s registration, the legislation provides that a deemed permit is taken to be issued, which may allow up to 1 year for phase-out of the cancelled product.

If the APVMA varies the instructions for use or conditions of a product’s registration, a phase-out period of 2 years is normally applied to allow phase-out of the product that has been varied if there is no imminent risk of serious illness or death from continued use of the products.

Further details of the chemical review process can be found on our website.

Enquiries about these updates should be directed to enquiries@apvma.gov.au or +61 2 6770 2300.

6. 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 February 2024.

Table 3 lists cancelled licences since April 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.