Source: https://www.tga.gov.au/book/export/html/734178
Timestamp: 2019-09-20 21:52:41
Document Index: 143428550

Matched Legal Cases: ['art 1', 'art 2', 'art 3', 'art 2', 'art 3', 'art 1', 'art 2', 'art 3', 'art 2', 'art 3']

Scheduling delegate&#039;s final decisions, January 2017
AQIS Australian Quarantine and Inspection Service (now Biosecurity)
NOHSC NOHSC
Implementation date: 1 February 2017.
2-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL except when in hair dye preparations containing 1.5 per cent or less of 2-chloro-6-(ethylamino)-4-nitrophenol when the immediate container and primary pack are labelled with the following statements:
An application was submitted to create a new Schedule 6 entry for 1,3-benzenediol for restriction in cosmetic and domestic products.
1,3-Benzenediol is not currently scheduled and has not been previously considered for scheduling; therefore, a scheduling history is not available. However, an isomer of 1,3-benzenediol, 1,2 benzenediol is currently scheduled as follows:
1,3-Benzenediol was reported to be used in permanent hair dye preparations in Australia (NICNAS, 2007) and in overseas hair lotions and shampoos.
Currently, there are no restrictions in Australia on using this chemical in hair dyes, hair lotions and shampoos. In the absence of any regulatory controls, the characterised critical health effects (skin and eye irritation, and skin sensitisation) have the potential to pose an unreasonable risk under the identified uses. The risk could be mitigated by implementing concentration limits and labelling requirements for use in hair dyes, hair lotions and shampoos.
The EU has restricted the use of this chemical in oxidative hair colouring products at a maximum concentration of 2.5%. It is mixed with hydrogen peroxide in a 1:1 ratio just prior to use, which corresponds to a concentration of 1.25% when applied to hair (SCCS, 2010). Restricted use in hair lotions and shampoos was also reported to be the maximum authorised concentration in the finished cosmetic product of 0.5%.
1,3-Benzenediol is listed on the EU Cosmetic Directive 76/768/EEC Annex III Part 1: List of substances which cosmetic products must not contain except subject to the restrictions and conditions laid down below (Galleria Chemica): (a) Hair dye substance in oxidative hair dye products for general and professional use-after mixing under oxidative conditions the maximum concentration applied to hair must not exceed 1.25% (w/w); and (b) Hair lotions and shampoos- maximum authorised concentration in the finished cosmetic product of 0.5% (w/w).
1,3-Benzenediol is also listed on the following:
1,3-BENZENEDIOL except:
in hair dye preparations containing 1.25 per cent or less of 1,3-benzenediol after mixing for use and when the immediate container and primary pack are labelled with the following statements:
in hair lotions/shampoo products containing 0.5 per cent or less of 1,3-benzenediol and when the immediate container and primary pack are labelled with the following statement:
Appendix E − 1,3-BENZENEDIOL
Appendix F − 1,3-BENZENEDIOL
1,3-Benzenediol is used in permanent hair dye preparations in Australia (NICNAS, 2007) and in hair lotions and shampoos overseas (refer to Import, Manufacture and Use section of IMAP Tier II report);
1,3-Benzenediol has moderate oral toxicity and has been shown to cause skin and eye irritation as well as skin sensitisation;
1,3-Benzenediol has existing overseas restrictions in European Union (EU) for oxidative hair colouring products at a maximum concentration of 2.5%, with labelling requirements at lower concentrations. It is mixed with hydrogen peroxide in a 1:1 ratio just prior to use, resulting in a concentration of 1.25% when applied to hair (SCCS, 2010). Use of the chemical is also restricted in hair lotions and shampoos with a maximum authorised concentration in the finished cosmetic product of 0.5%; and
When 1,3-benzenediol is used as a hair dye, there is a potential risk of for skin sensitisation, which may be controlled through concentration restrictions and warning labels, as have previously been applied to other sensitising hair dyes considered for inclusion in the SUSMP.
The following toxicology information was extracted from the NICNAS IMAP Human Health Tier II assessment. Further information can also be found in the European Commission Scientific Committee on Consumer Safety (SCCS) report.
Figure 1.2: Chemical structure of 1,3-benzenediol
Table 1.2A: Chemical properties and identifiers of 1,3-benzenediol
Molecular weight 110.1°g/mol
IUPAC and/or common and/or other names Resorcinol (INCI name); benzene-1,3-diol (IUPAC); 1,3-dihydroxybenzene; and 3-hydroxyphenol.
Table 1.2B: Acute toxicity end-points for 1,3-benzenediol
Acute oral toxicity LD50 (mg/kg bodyweight (bw)) Rats (Sprague Dawley) 200-980 mg/kg bw/day. N/A
Acute dermal toxicity LD50 (mg/kg bw) Rabbits > 2000 mg/kg bw/day. N/A
> 7800 mg/m 3/1–hour (equivalent to 7.8 mg/L or 1732 ppm); and
> 2800 mg/m 3/8–hours (equivalent to 2.8 mg/L or 622 ppm)
Rabbit (New Zealand White) Not irritating to skin (2.5% solution in water; 98.8% purity)
Skin sensitisation (Guinea Pig Maximisation Test: GPMT) Guinea pigs (Pirbright white) Sensitiser (relative incidence of the positive reactions in animals was > 30%) (99.9% purity) Schedule 6
The acute toxicity end-points of 1,3-benzenediol are summarised in Table 1.2B.
In a study conducted according to the OECD Test Guideline 404 (acute dermal irritation/corrosion), 0.5 mL of the chemical (2.5% aqueous solution) (98.8% purity) was applied to the clipped back skin of New Zealand White rabbits (three males/group) for four hours under semi-occlusive patches. Observations were made at one, 24, 48 and 72 hours post-treatment. No adverse cutaneous reactions were reported at this low concentration.
In a study conducted according to OECD TG 405 (acute eye irritation/corrosion), 0.1 mL of the chemical (2.5% solution in water (98.8% purity)) was instilled into the eyes (conjunctival sacs) of New Zealand White rabbits (three males) and left for 72 hours. Mean scores of zero were reported for chemosis, iris lesions and corneal opacity over 24, 48 and 72 hours. For redness of the conjunctivae, a mean score of 0.1 was reported.
In a GPMT conducted in accordance with OECD TG 406, Pirbright white guinea pigs (treatment group 10 animals, control group 5 animals and accompanying group 20 animals used for range finding) were administered 2% (w/v) solution of the chemical (99.9% purity as white flakes in sodium chloride) by intradermal injection followed by occlusive, epicutaneous application of 25% the chemical. At the challenge exposure using 25% of the chemical (occlusive epicutaneous application), very slight to distinct erythema was observed on the skin of 2-3 animals at 24 and 48 hours observation periods. At the second challenge and compared to the control group, very slight to distinct erythema was reported in 7/10 guinea pigs at 24 hours and on 5/10 guinea pigs at 48 hours and minor swelling was also observed in one animal at 24 hours after patch removal. The relative incidence of the positive reactions in animals was over the threshold value of 30% and the chemical was considered to be a skin sensitiser;
In a study conducted in accordance with OECD TG 429, positive skin sensitisation was reported in LLNA studies in two independent experiments. A positive control of a-hexyl cinnamaldehyde (HCA), a moderate sensitiser, at the concentration of 25% (v/v) in DMF was used. In the first experiment (range finding), female CBA/J mice (four animals/dose including negative and positive controls) were administered 25 μL of the chemical (in vehicle dimethylformamide at 2.5, 5, 10, 25 or 50%) applied to the dorsal surface of each ear, once daily for three consecutive days. Stimulation indices (SI) of 3.83, 4.14, 3.97, 3.51 and 3.30 were reported, respectively. Positive lymphoproliferative responses (SI > 3) were reported at all concentrations, but no clear dose-response relationship was observed. In the second experiment, mice (four/dose) were administered daily applications of 0.1, 0.5, 1, 5 or 25% chemical (w/v). Treatment resulted in stimulation indices of 1.58, 2.87, 1.97, 3.51 and 5.74, respectively. A dose-related increase in SI was seen and the threshold positive value of three was exceeded. The effective concentration at which a three-fold increase in SI was achieved (EC3) was reported to be 1.4% and the chemical was considered to be a moderate skin sensitiser; and
The chemical (purity unspecified) was not reported to be sensitising according to two non-guideline skin sensitisation (LLNA) studies in mice (concentrations of up to 2.5% and 25% w/v were tested, respectively). No further study details were available and the reliability of both studies was questioned due to out-dated study methods (OECD, 2008). However, the chemical was reported to be a sensitiser in mice in a LLNA study (OECD TG 429). A group of CBA/Ca female mice (four/dose) were treated at daily concentrations of 0, 1, 5, 10, 25 and 50% (w/v) of the chemical (purity unspecified) in acetone/olive oil (ratio of 4:1). SIs of 1.0, 0.7, 2.2, 5.2, 8.4 or 10.4 were measured respectively, and an EC value of 6.3% was determined (REACH; OECD, 2008).
Human patch-testing using 1,3-benzenediol elicited allergic skin reactions in 0.7–0.8% of 1694 dermatitis patients. In further case histories of 34 dermatitis patients, the chemical was reported to cause reactions after epicutaneous testing.
In human patch tests with the chemical (2% in petrolatum), four out of 302 hairdressers suffering from contact dermatitis reported a positive reaction. No further details were available. In another case, one patient who developed contact dermatitis after application of paint to the skin was patch tested with the chemical (5% in petrolatum) and showed a positive result after 48 hours. In a third case, three female patients suffering from acne and contact dermatitis gave a positive patch test for the chemical (2% in petrolatum) after 48 and 72 hours.
NICNAS IMAP Tier II Report;
Scheduling Policy Framework (SPF 2015) criteria; and
The delegate's final decision is to create a new Schedule 6 entry for 1,3-benzenediol with a 1.25 per cent exemption cut-off in hair dye preparations as follows:
Appendix E, Part 2 – RESORCINOL
Appendix F, Part 3 – RESORCINOL
The delegate notes that the main routes of exposure to resorcinol is through the skin and eyes from products applied to the hair and scalp. The skin and eye irritation and skin sensitisation of resorcinol are consistent with Schedule 6 criteria. Recent decisions for previously considered similar sensitising hair dyes have allowed for some products to be exempted where there are label statements warning of the potential for skin irritancy and sensitisation, and recommending testing for individual susceptibility before use. This scheduling decision is in alignment with international regulations for resorcinol and is consistent with recent decisions agreed on previously considered similar sensitising hair dyes.
On this page: Referred scheduling proposal | Current scheduling status and relevant scheduling history | International regulations | Scheduling application | Substance summary | Delegate's considerations | Delegate's final decision
An application was submitted to create a new entry for 2-chloro-6-(ethylamino)-4-nitrophenol in Schedule 6 to restrict its use in hair dyes and to determine whether an appropriate exemption concentration cut-off is required.
2-Chloro-6-(ethylamino)-4-nitrophenol is not currently scheduled and has not been previously considered for scheduling; therefore, scheduling history is not available.
However, a homologue of 2-chloro-6-(ethylamino)-4-nitrophenol, 2-amino-6-chloro-4-nitrophenol is currently listed in Schedule 6 for use in hair dye and eyebrow/eyelash colouring preparations as follows:
2-AMINO-6-CHLORO-4-NITROPHENOL in hair dye and eyebrow/eyelash colouring preparations, except:
in preparations containing 2 per cent or less of 2-amino-6-chloro-4-nitrophenol when applied directly to the hair, or containing 2 per cent or less of 2-amino-6-chloro-4-nitrophenol after mixing and when the immediate container and primary pack are labelled with the following statements:
b)	in eyelash and eyebrow tinting products containing 1.5 per cent or less of 2-amino-6-chloro-4-nitrophenol after mixing for use when the immediate container and primary pack are labelled with the following statement:
Appendix E, Part 2 − 2-AMINO-6-CHLORO-4-NITROPHENOL
Appendix F, Part 3 − 2-AMINO-6-CHLORO-4-NITROPHENOL
Use of the chemical in cosmetics in the European Union (EU) is subject to the restrictions described in EU Cosmetics Regulation 344/2013 (as an amendment to the listing under Annex III of Regulation 1223/2009). This chemical may be used at maximum concentrations of 3.0% in ready-for-use preparations of oxidising (permanent) and non-oxidising (semi-permanent) colouring agents for hair dyeing. Additionally, after mixing under oxidative conditions (i.e. with hydrogen peroxide) the maximum concentration applied to hair must not exceed 1.5% for both permanent and semi-permanent application types. The Cosmetics Regulation also mandates label warning statements relating to the sensitisation potential of the chemical.
Use of the chemical in hair dyes is also restricted in several other countries as according to inclusion in the following listings:
the Association of Southeast Asian Nations (ASEAN) Cosmetic Directive Annex III-Part 1, with the same use restrictions as described above for the EU; and
the New Zealand Cosmetic Products Group Standard-Schedule 5-Table 1: Components cosmetic products must not contain except subject to restrictions and conditions laid down. While a maximum concentration (of 3.0%) only appears to apply to ready for use preparations of non-oxidising (semi-permanent) colouring agents for hair dyeing, the maximum concentration applied to hair must not exceed 1.5% for both permanent and semi-permanent application types.
2-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL except when used in hair dye and eyebrow/eyelash colouring products at a concentration of 1.5 per cent or less of 2-chloro-6-(ethylamino)-4-nitrophenol after mixing for use and when the immediate container and primary pack are labelled with the following statements:
Appendix E, Part 2 − 2-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL
Appendix F, Part 3 − 2-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL
Reported use of 2-chloro-6-(ethylamino)-4-nitrophenol as an ingredient in both permanent and semi-permanent hair dyes in Australia;
2-Chloro-6-(ethylamino)-4-nitrophenol is a skin sensitiser;
2-Chloro-6-(ethylamino)-4-nitrophenol is acutely toxic following oral exposure;
Overseas restrictions for use of 2-chloro-6-(ethylamino)-4-nitrophenol in hair dyes; and
When 2-chloro-6-(ethylamino)-4-nitrophenol is used as a hair dye, there is a potential risk of for skin sensitisation, which may be controlled through concentration restrictions and warning labels, as have previously been applied to other sensitising hair dyes considered for inclusion in the SUSMP.
The following toxicology information was extracted from the NICNAS IMAP Human Health Tier II assessment report for phenol, 2-chloro-6-(ethylamino)-4-nitro-.
Figure 1.3: Chemical structure of 2-chloro-6-(ethylamino)-4-nitrophenol
Table 1.3A: Chemical properties and identifiers of 2-chloro-6-(ethylamino)-4-nitrophenol
Molecular formula C8H9ClN2O3
Molecular weight 216.62 g/mol
CAS name Phenol, 2-chloro-6-(ethylamino)-4-nitro-
CAS number 131657-78-8
IUPAC and/or common and/or other names 2-Chloro-6-(ethylamino)-4-nitrophenol (INCI name)
Table 1.3B: Acute toxicity end-points for 2-chloro-6-(ethylamino)-4-nitrophenol
Acute oral toxicity LD50 (mg/kg bodyweight (bw)) Rat 1728 Schedule 6
Acute inhalational toxicity LC50 (mg/m3/4h) - No data N/A
Skin irritation Rabbit Not irritating to the skin N/A
Eye irritation Rabbit Insufficient data. N/A
2-Chloro-6-(ethylamino)-4-nitrophenol has moderate acute oral toxicity, but low acute dermal toxicity based on results from animal tests. Additionally, the chemical is classified as hazardous with the risk phrase 'Harmful if swallowed' (Xn; R22) in the HSIS. The available data support this classification.
The available data from animal studies indicate that 2-chloro-6-(ethylamino)-4-nitrophenol is not irritating to the skin, but is a potential eye irritant. However, insufficient details on the eye irritation study are available, which do not allow for hazard classification.
2-Chloro-6-(ethylamino)-4-nitrophenol is classified as hazardous with the risk phrase 'May cause sensitisation by skin contact' (R43) in the HSIS. The positive results, reported in a local lymph node assay (LLNA), support this classification.
In an LLNA conducted according to OECD TG 429, the skin sensitising potential of 2 chloro 6 (ethylamino)-4-nitrophenol was tested in mice (5 animals/dose group) at concentrations ranging from 0.5–10% using a DMSO vehicle, and at 0.5–2.5% using an acetone/water/olive oil vehicle (mix ratio of 2:2:1). The estimated concentration needed to produce a three-fold increase in lymphocyte proliferation (EC3) value of 2.79% was determined based on the concentrations used with the DMSO vehicle; a stimulation index greater than three was not observed at the lower concentrations used with the acetone/water/olive oil vehicle (up to 2.5%).
Based on the available information, 2-chloro-6-(ethylamino)-4-nitrophenol is not considered to cause serious damage to health through repeated oral exposure.
Based on the weight of evidence from the available, well-conducted, in vitro and Delegate's considerations
The delegate's final decision is to create a new Schedule 6 entry for 2 chloro 6 (ethylamino) 4 nitrophenol with a 1.5 per cent cut-off of 2 chloro 6 (ethylamino) 4 nitrophenol after mixing for use in hair dye preparations as follows:
Appendix E, Part 2 – 2-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL
Appendix F, Part 3 – 2-CHLORO-6-(ETHYLAMINO)-4-NITROPHENOL
The delegate notes that the main route of exposure to 2-chloro-6-(ethylamino)-4-nitrophenol is through the skin. The acute oral toxicity and skin sensitisation are consistent with Schedule 6 criteria. Recent decisions for previously considered similar sensitising hair dyes have allowed for some products to be exempted where there are label statements warning of the potential for skin sensitisation, and recommending testing for individual susceptibility before use. This scheduling decision is in alignment with international regulations for 2-chloro-6-(ethylamino)-4-nitrophenol and is consistent with recent decisions agreed on previously considered similar sensitising hair dyes.
Substance	Final decision
LUMACAFTOR.
The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of cobimetinib, a NCE for a human therapeutic medicine.
Cobimetinib is a highly selective allosteric inhibitor that targets MEK1 and MEK2 tyrosine-threonine kinases. It has shown high inhibitory potency in biochemical and cell based assays, as well as broad anti-tumour activity in vivo in xenograft tumour models, including those that are mutated for BRAF and KRAS.
Cobimetinib is indicated for use in combination with vemurafenib for the treatment of patients with un-resectable or metastatic melanoma with BRAF V600 mutation.
AAN – Cobimetinib
Cobimetinib is not specifically scheduled and is not captured by any entry in the current Poisons Standard.
Cobimetinib is not classified in New Zealand.
The delegate has made a final decision to amend the Poisons Standard to include cobimetinib in Schedule 4, with an implementation date of 1 February 2017.
Benefit/risk balance is considered positive for the approved use, but there is limited clinical experience with the product in Australia;
cobimetinib is indicated for use in combination with vemurafenib for the treatment of patients with un-resectable or metastatic melanoma with BRAF V600 mutation;
Toxicity was considered in TGA review of initial application and is addressed under benefit/risk balance above;
The dosage, formulation, labelling, packaging and presentation were considered satisfactory in a TGA review of the initial application; and
The potential for abuse was considered to be nil by the TGA when reviewing the initial application.
The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of lenvatinib, a new chemical entity (NCE) for a human therapeutic medicine.
Lenvatinib is a multiple receptor tyrosine kinase (RTK) inhibitor that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4), in addition to other proangiogenic and oncogenic pathway-related RTKs including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4, the platelet derived growth factor (PDGF) receptor PDGFRα, KIT, and RET.
AAN – Lenvatinib
Lenvatinib is not specifically scheduled and is not captured by any entry in the current Poisons Standard.
Lenvatinib is not classified in New Zealand.
The delegate has made a final decision to amend the Poisons Standard to include lenvatinib in Schedule 4, with an implementation date of 1 February 2017.
Lenvatinib is indicated for the treatment of patients with progressive, locally advanced or metastatic, radioactive iodine refractory differentiated thyroid cancer;
The dosage, formulation, labelling, packaging and presentation were considered satisfactory in the TGA review of the initial application; and
The potential for abuse was considered to be nil in a TGA review of the initial application.
The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of talimogene laherparepvec, a new chemical entity (NCE) for a human therapeutic medicine.
Talimogene laherparepvec is a modified herpes simplex virus type 1 (HSV-1) encoding GM-CSF.
ABN – Talimogene laherparepvec
Talimogene laherparepvec is not specifically scheduled and is not captured by any entry in the current Poisons Standard.
Talimogene laherparepvec is not classified in New Zealand.
Other [OGTR reports].
The delegate has made a final decision to amend the Poisons Standard to include talimogene laherparepvec in Schedule 4, with an implementation date of 1 February 2017.
The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are: (a) the risks and benefits of the use of a substance; (b) the purpose 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; (e) the potential for abuse; and (f) any other matters that the Secretary considers necessary to protect public health.
talimogene laherparepvec is indicated as monotherapy for the treatment of melanoma in patients with unresectable cutaneous, subcutaneous or nodal lesions after initial surgery;
Dosage, formulation, labelling, packaging and presentation were considered satisfactory in a TGA review of the initial application;
The potential for abuse was considered to be nil in a TGA review of the initial application;
Environmental/person-to-person spread considered under benefit/risk balance above.
The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of fomepizole, a NCE for a human therapeutic medicine.
Fomepizole is an alcohol dehydrogenase inhibitor for the treatment of methanol and ethylene glycol poisoning and acts to inhibit the breakdown of these toxins into their active toxic metabolites.
Fomepizole is indicated for the treatment of methanol or ethylene glycol poisoning.
Table 2.7: Properties, identifiers and naming of fomepizole
Molecular weight 82.11 g/mol
Chemical name/s 4-methyl-1H-pyrazole; 4-methylpyrazole
AAN Fomepizole
Fomepizole is not specifically scheduled and is not captured by any entry in the current Poisons Standard.
Fomepizole is on the World Health Organization (WHO) Model List of Essential Medicines as an essential medicine for priority diseases.
Fomepizole is available as a prescription only drug in the USA, Canada and New Zealand.
The advice of the Advisory Committee on Prescription Medicines (ACPM); and
The delegate has made a final decision to amend the Poisons Standard to include fomepizole in Schedule 4, with an implementation date of 1 February 2017.
It is a new chemical entity with no clinical experience in Australia;
The risks and benefits of the medicine have been considered and are outlined in the Product Information, Delegate's Request for ACPM advice and the TGA evaluation reports;
Fomepizole is indicated as an antidote for the treatment of ethylene glycol or methanol poisoning;
It has no previous experience of use in Australia but has been approved for many years overseas;
It is proposed for use in hospitals;
Fomepizole is a competitive inhibitor of alcohol dehydrogenase;
The medicine has risks that may require medical intervention, evaluation and monitoring by a medical practitioner;
Labelling needs to comply with the requirements for a prescription only medicine; and
The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of osimertinib, a NCE for a human therapeutic medicine.
For the delegate to consider the scheduling of the NCE, osimertinib.
Osimertinib is an irreversible inhibitor of mutant forms of epidermal growth factor receptor (EGFR) found in non-small cell lung cancer (NSCLC).
Osimertinib is indicated for the treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive non-small cell lung cancer.
AAN – Osimertinib
Osimertinib is not specifically scheduled and is not captured by any entry in the current Poisons Standard.
Osimertinib is not classified in New Zealand.
The delegate has made a final decision to amend the Poisons Standard to include osimertinib in Schedule 4, with an implementation date of 1 February 2017.
The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are: (a) the risks and benefits of the use of a substance; (b) the purpose 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. The delegate decided that the reasons for the final decision comprise the following:
It is a new chemical entity with limited clinical experience in Australia;
The conclusion of the TGA evaluation was that a positive benefit / risk balance exists in the specified target population;
Osimertinib is indicated for the treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive non-small cell lung cancer; and
The potential for abuse of osimertinib is unlikely.
The delegate considered an application from the Therapeutic Goods Administration for the scheduling of lipegfilgrastim, a NCE for a human therapeutic medicine.
Lipegfilgrastim is a long-acting covalent conjugate of filgrastim with methoxy polyethylene glycol (PEG) via a carbohydrate linker.
AAN – Lipegfilgrastim
Lipegfilgrastim is not specifically scheduled and is not captured by any entry in the current Poisons Standard.
Lipegfilgrastim is not classified in New Zealand.
The delegate has made a final decision to amend the Poisons Standard to include lipegfilgrastim in Schedule 4, with an implementation date of 1 February 2017.
The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are: (a) the risks and benefits of the use of a substance.
It is a NCE with no clinical/marketing experience in Australia;
the condition being treated (neutropenia or febrile neutropenia) necessitates an appropriate diagnosis for the use of this medicine, and for ongoing patient management and monitoring, by a medical professional; and
The potential for abuse of lipegfilgrastim is unlikely.
The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of elotuzumab, a new chemical entity (NCE) for a human therapeutic medicine.
Elotuzumab is a humanised, IgG1 monoclonal antibody (mab) that specifically binds to human Signalling Lymphocyte Activation molecule family member 7 (SLAMF7) proteins. It consists of the complimentary determining regions of the parent mouse antibody, MuLuc63, grafted onto human IgG1 heavy chain and kappa light chain regions. SLAMF7 is highly expressed in MM cells independent of diseases stage or cytogenetic abnormalities. SLAMF7 is also expressed on natural killer (NK) cells, natural killer T cells (NKT), plasma cells and on specific immune subsets (CD8+T and CD4+ T cells) but is not detected on hematopoietic stem cells or on most normal tissues. Binding of elotuzumab to NK cells directly activates immune cells through both the SLAMF7 and CD16 pathways enhancing anti-myeloma activity in vitro. Elotuzumab also binds to the SLAMF7 protein on myeloma cells and facilitates the interaction of NK cells with myeloma cells to mediate the killing of these malignant cells through antibody-dependent cellular cytotoxicity (ADCC). In preclinical models, elotuzumab has single-agent anti-MM activity and can synergize with lenalidomide and bortezomib to further enhance this activity.
AAN – Elotuzumab
Elotuzumab is not specifically scheduled and is not captured by any entry in the current Poisons Standard.
Elotuzumab is not classified in New Zealand.
The TGA evaluation report;,
The delegate has made a final decision to amend the Poisons Standard to include elotuzumab in Schedule 4, with an implementation date of 1 February 2017.
The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are: (a) the risks and benefits of the use of a substance; and (b) the purpose and the extent of use of a substance.
Elotuzumab has risks of infections, second primary malignancies, hepatotoxicity and infusion related reactions;
Treatment should be initiated and supervised by physicians experienced in the treatment of multiple myeloma;
Elotuzumab is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy; and
The potential for abuse of elotuzumab is unlikely.
The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of ixazomib (as citrate), a NCE for a human therapeutic medicine.
Ixazomib (as citrate) is a 20S proteasome inhibitor for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. It is indicated for the treatment of patients with multiple myeloma who have received at least one prior therapy.
AAN – Ixazomib/ixazomib citrate
Ixazomib (as citrate) is not specifically scheduled and is not captured by any entry in the current Poisons Standard.
Ixazomib (as citrate) is not classified in New Zealand.
The delegate has made a final decision to amend the Poisons Standard to include ixazomib in Schedule 4, with an implementation date of 1 February 2017.
Ixazomib has risks of neuropathy, infections, neutropaenia and thrombocytopaenia;
Ixazomib is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy; and
The potential for abuse of ixazomib is unlikely.
The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of lumacaftor, a NCE for a human therapeutic medicine.
Lumacaftor is a selective CFTR corrector that acts on F508del-CFTR to increase the amount of functional CFTR at the cell surface to enhance chloride transport. Lumacaftor acts on CFTR to facilitate the cellular processing and trafficking of CFTR, allowing the protein to reach the cell surface, where it exhibits improved chloride channel function compared to uncorrected F508del-CFTR. F508del-CFTR that has been delivered to the cell surface by lumacaftor can be further potentiated by ivacaftor. Lumacaftor can increase the amount of normal CFTR at the cell surface and can correct certain other CFTR forms, including certain mutations that cause defects in processing. Ivacaftor has been shown to have CFTR potentiator properties.
AAN – Lumacaftor.
Lumacaftor is not specifically scheduled and is not captured by any entry in the current Poisons Standard.
Lumacaftor is not classified in New Zealand.
The delegate has made a final decision to amend the Poisons Standard to include lumacaftor in Schedule 4, with an implementation date of 1 February 2017.
It is a NCE with no clinical/marketing experience in Australia; and
The potential for abuse of lumacaftor is unlikely.
The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of sodium zirconium cyclosilicate, a NCE for a human therapeutic medicine.
Sodium zirconium cyclosilicate is a highly selective cation exchanger that entraps potassium in the intestinal tract in exchange for sodium and hydrogen.
AAN – sodium zirconium cyclosilicate
Sodium zirconium cyclosilicate is not specifically scheduled and is not captured by any entry in the current Poisons Standard.
Sodium zirconium cyclosilicate is not classified in New Zealand.
The delegate has made a final decision to amend the Poisons Standard to include sodium zirconium cyclosilicate in Schedule 4, with an implementation date of 1 February 2017.
The intended use is the treatment of hyperkaelemia;
This medicine is not absorbed, it acts locally in the gastrointestinal tract; and
The potential for abuse of sodium zirconium cyclosilicate is unlikely.
The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of sonidegib diphosphate, a new chemical entity (NCE) for a human therapeutic medicine.
Sonidegib diphosphate is a potent, selective, and orally bioavailable smoothened (Smo) antagonist. Smoothened is a transmembrane G protein-coupled receptor-like molecule that positively regulates the Hedgehog (Hh) signal transduction pathway.
AAN – Sonidegib diphosphate
Sonidegib diphosphate is not specifically scheduled and is not captured by any entry in the current Poisons Standard.
Sonidegib diphosphate is not classified in New Zealand.
The delegate has made a final decision to amend the Poisons Standard to include sonidegib in Schedule 4, with an implementation date of 1 February 2017.
It is a NCE with no clinical experience in Australia;
Sonidegib is Pregnancy Category X (as is the first in class Vismodegib) but its use is in a restricted population and likely to be under close supervision of appropriately specialized physicians, therefore label warnings are not considered necessary at this stage; and
The potential for abuse of sonidegib is unlikely.