This guidance applies only to veterinary immunobiological products intended for food-producing animals.
1.1. Objective of the guidance
This document describes the Health (previously referred to as Part 3 Toxicology) and Residue data requirements for an immunobiological product containing an adjuvant not contained in a registered vaccine for food producing animals.
The Australian Pesticides and Veterinary Medicine Authority (APVMA) Data Guidelines for Health (previously referred to as Part 3, Toxicology), outline the relevant data that should be provided when an assessment of a new veterinary chemical (including novel adjuvants) is required. These data must provide information on the potential human health hazards arising from proposed uses of the veterinary chemical product and is important in establishing:
- acceptable daily intakes (ADIs)
- acute reference doses (ARfDs)
- poison schedule classifications
- first aid instructions
- safety directions
- any necessary warning statements.
Additionally, the APVMA must be satisfied that foodstuffs obtained from animals treated with an active constituent or chemical product do not contain residues of the active constituent, or its metabolites, which might constitute a health hazard for the consumer. The Residues Data Guidelines provide details of the types of data that the APVMA can use to establish this.
Adjuvants are additives that may be added to an immunobiological product to enhance the immunogenicity of the antigen. Immunobiological products for food-producing animals often involve only a single or very few administrations to the animal, and these administrations are most frequently given weeks or months in advance of the animal becoming part of the food chain. Therefore, there is limited use of the product, limited exposure and minimal opportunity for cumulative toxic effect. The nature of the immune system is such that it may take up to 3 weeks after the last administration in a dosing regime to have effect, so this class of products are generally administered well in advance of animal slaughter.
Toxicity data are not normally required for new veterinary immunobiological products, but may be required where a novel adjuvant(s) is used. Residues data are also not normally required for veterinary immunobiological products but may be required in some circumstances where novel adjuvants are used in vaccines administered to food-producing animals.
2.1. Description of the adjuvant
Precise identification of the substance or product concerned must be provided. This includes:
- International Non-proprietary Name (INN)
- International Union of Pure and Applied Chemistry (IUPAC) name
- Chemical Abstract Service (CAS) name and number
- classification (therapeutic, pharmacological)
- material safety data sheet (MSDS)
- generic name of adjuvant (and trade name if applicable)
- chemical composition of adjuvant, including all ingredients and amounts
- amount of total adjuvant per dose of product and dose volume of product
- information regarding source, grade, and quality of each adjuvant lot
- specific testing on adjuvant lots prior to use
- other products for which the adjuvant has been approved (if applicable).
- information regarding source, grade, and quality of adjuvant
- other relevant information.
Where the information is not available to the applicant due to confidential commercial considerations, it is acceptable for the adjuvant manufacturer or supplier to provide the information directly to the APVMA (with appropriate cross-reference to the application under consideration).
2.2. Health assessment
A Health 3 module would normally be required. However, in instances where the adjuvant is registered for use in human immunological products, a Health 4 may be applicable. In addition to the information listed in 2.1 above, the toxicological data submitted in support of the application should include studies on the novel adjuvant and/or studies on the product containing the novel adjuvant or submission of valid scientific argument not to submit certain studies.
The following information would normally be required:
- Any information relative to the listing of the adjuvant on lists of approved additives, e.g. pharmacopoeia
- The results of toxicological studies to determine the local and systemic effects of the adjuvant on laboratory animals
- Summary of any oral/acute testing of the adjuvant in target and non-target species
- Summary of any information available regarding the metabolism of the adjuvant
- Any information available regarding the genotoxicity or reproductive and/or developmental toxicity of the adjuvant
- Any known reactivity of the adjuvant
- Pharmacological activity of the adjuvant
- Any reported adverse findings associated with the use of the adjuvant in humans
Submission of an acceptable overseas health risk assessment report and a data package containing all of the studies associated with that report may be submitted to address the toxicological data requirements noted above.
Residues assessment may be required where novel adjuvants are used in vaccines administered to food-producing animals. The assessment is likely to be done as a Residues 4 module.
When a residues data package is required, in addition to the information in 2.1 above, the application should include submission of a human exposure profile, which should include studies on the adjuvant and/or studies on the product, or submission of valid scientific argument not to submit certain studies.
The following information may be required, as available:
- Estimate of the total volume/mass of the adjuvant that will be administered to the target animal under the proposed instructions for use
- Estimate of the human consumption/exposure to the adjuvant
- Levels of residue in animal tissue at proposed withdrawal period
- Tolerance level established for adjuvant, if known (cite source, for example, MRL assessment in another jurisdiction such as the EMEA or US FDA).
2.4. Special requirements for nanomaterials
The APVMA’s working definition of a nanomaterial is ‘an intentionally produced, manufactured or engineered substance with unique properties that are directly caused by size features, with 10% or more of the number size distribution of these features lying in the range approximately 1 to 100 nm (the nanoscale).’
Applicants are required to advise the APVMA when a vaccine contains nanomaterial.
The risk assessment of the proposed vaccine requires that the form of nanomaterials used in toxicology studies be well characterised. The ‘Report of the OECD Expert Meeting on the Physical and Chemical Properties of Manufactured Nanomaterials and Test Guidelines’, No 41 outlines the process to characterise nanomaterials. The toxicological endpoints prescribed in the APVMA data guidelines for non-nanoscale materials are appropriate for assessing the hazards of nanomaterials. The current risk assessment approaches used by FAO/WHO and Codex for residues in food are suitable for nanomaterials. However, any additional safety concerns arising from the characteristic properties of nanomaterials need to be addressed.
- Veterinary Services Memorandum No. 800.51: Additives in Animal Biological Products
- EMEA (CVMP) Notice to applicants and Guideline – Veterinary medicinal products – Establishment of maximum residue limits (MRLs) for residues of veterinary medicinal products in foodstuffs of animal origin