4.3 Tigilanol tiglate

4 Final decisions on proposed amendments to the current Poisons Standard under regulation 2ZCZU

4.3 Final decision in relation to tigilanol tiglate

Final decision

Pursuant to regulation 42ZCZU of the Regulations, a Delegate of the Secretary has made a final decision to amend the current Poisons Standard in relation to tigilanol tiglate as follows:

Materials considered

In making this final decision, the Delegate considered the following material:

• The application to amend the current Poisons Standard with respect to tigilanol tiglate;
• Subsection 52E(1) of the Therapeutic Goods Act 1989, in particular (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; and (e) the potential for abuse of a substance; and (f) any other matters considered necessary to protect public health;
• The Australian Health Ministers' Advisory Council's Scheduling Policy Framework (SPF 2018); and
• The Scheduling handbook: Guidance for amending the Poisons Standard.

Reasons for the final decision (including findings on material questions of fact)

In determining, that this matter will be a delegate-only decision I have taken into account the information provided in the application from the Applicant (APVMA), and the matters outlined under Section 52E of the Therapeutic Goods Act 1989 and the Scheduling Policy Framework (2018). In particular, I note that:

• The proposed change to the Poisons Standard to include a new entry for tigilanol tiglate indicates that there are benefits to the veterinary medicine industry from the introduction of this new therapeutic agent for the treatment of mast cell tumours in dogs. The proposed product contains 1 mg/mL of tigilanol tiglate. The product is intended to be administered by veterinarians by intra-tumoral injection. The most likely human exposure to the substance, may be the result of accidental needle stick injury, but adverse effects are considered limited to local inflammatory reactions at the site of self-injection. Accidental eye exposure has been reported that resulted in transient eye irritation. The applicant has recommended appropriate label statements to mitigate these risks. Moreover, exposure to the substance to pet owners or the general public following treatment, is anticipated to be very limited given that the administration is via intra-tumoral injection and very limited residual substance is expected to remain on the treated animal's skin (52E(1)(a)).
• The purposes and extent for which the substance is to be used has been adequately outlined by applicant, i.e. for the treatment of cutaneous and subcutaneous mast cell tumours in dogs. The product containing tigilanol tiglate will only be made available for use by registered veterinarians based on the requirement for the diagnosis and management of the condition by suitably trained individuals (veterinarians), and the high level of expertise required for the administration of the product by a controlled injection method (52E(1)(b)).
• Single and repeat dose toxicity studies were conducted with tigilanol tiglate, along with target animal safety studies. The main findings were injection site inflammation after subcutaneous injection and hypotension following intravenous dosing. Tigilanol tiglate was not genotoxic in a battery of in vivo and in vitro tests. Carcinogenicity and multigenerational reproductive toxicity studies were not conducted; but these were not considered necessary by the regulator based on the proposed use pattern, in particular as the product is not intended for use in food producing species (52E(1)(c)).
• Studies with the proposed product, included an acute dermal toxicity in nude mice (which revealed low acute dermal toxicity), an in vitro skin irritation study (the product was classified as a skin irritant) and an in vitro ocular irritation study (the product was not classified as an ocular irritant). No sensitisation studies were conducted (52E(1)(c)).
• The toxicity profile and use pattern of tigilanol tiglate is such that it meets the factors for inclusion in Schedule 4 of the SUSMP (52E(1)(c)).
• The applicant has demonstrated that appropriate risk mitigation measures will be put in place for the proposed product containing tigilanol tiglate that may be registered for use in Australia, and that account for the dosage (application rate), formulation, labelling, packaging and presentation of tigilanol tiglate. As a result, no additional measures are required in the Poisons Standard. Further use of tigilanol tiglate in other products will be addressed by the veterinary chemicals regulator (APVMA) in any future applications to the regulator (53E(1)(d)).
• There is no information to indicate that the substance could pose a risk to humans from abuse of the substance (52(E)(1)(e)).

Therefore, based on the information provided in the application, I have decided to amend the current Poisons Standard in the manner set out in the application. The proposed amendment was not referred to an expert advisory committee.

Date of effect of the decision

1 October 2020