FinalDecisions & Reasons for Decisions byDelegates of the Secretary to the Department of Health and Ageing
JUNE 2011
Delegates’ final decisions on scheduling matters:
- Initially referred to the February 2011 meeting of the Advisory Committee on Chemicals Scheduling (ACCS) [ACCS#1];
- Initially referred to the February 2011 meeting of the Advisory Committee on Medicines Scheduling (ACMS) [ACMS#2];
- Initially referred to the February 2011 joint meeting of the ACCS and the ACMS [ACCS-ACMS#2]; or
- Considered as delegate-only matters i.e. were not referred to an advisory committee.
Notice under subsections 42ZXZS and 42ZCZX of the Therapeutic Goods Regulations 1990 (the Regulations)
A delegate of the Secretary to the Department of Health and Ageing hereby gives notice of delegates’ final decisions for amending the Poisons Standard (commonly referred to as the Standard for the Uniform Scheduling of Medicines and Poisons – SUSMP) under subsections 42ZCZS and 42ZCZX of the Regulations. This notice also provides the reasons for each decision and the date of effect of the decision. Edited versions of further submissions on interim decisions for matters referred to ACCS#1, ACMS#2 or ACCS-ACMS#2 are also available at
Matters referred to ACCS#1, ACMS#2 and ACCS-ACMS#2
Delegate’s interim decisions on recommendations by ACCS#1, ACMS#2 and ACCS-ACMS#2 were published on 27 April 2011, accessible at This public notice also invited further comment from the applicant and from those parties who made a valid submission in response to the original invitation for submissions (published 15December 2010, together with a supplementary invitation published 16December2010 – both accessible at
In accordance with subsection 42ZCZR of the Regulations, if a delegate makes an interim decision on an application, that delegate may make a final decision confirming, varying or setting aside the interim decision only after considering any further valid submissions. If no further submissions were received then the delegate may choose to confirm the interim decision as the final decision.
Further submissions from parties other than those who made a valid submission in response to the original invitation or the applicant, or those received after the closing date, need not be considered by the delegate.
Matters not referred to an advisory committee
A delegate may decide not to refer a matter to an advisory committee and instead may make a final decision on matters. Guidance for the delegate when deciding not to refer a matter to an advisory committee is set out in the Scheduling Policy Framework (SPF) accessible at
Implementation
The amendments arising from this notice will be incorporated into the SUSMP through an amendment which will be available for purchase from National Mailing and Marketing Pty Ltd, telephone (02) 6269 1035. The SUSMP and its amendments are also available electronically at the ComLaw website, a link to which can be found at
Delegates’ reasons for final decisions
June 20111
TABLE OF CONTENTS
GLOSSARY......
PART A – FInal Decisions on Matters REFERRED TO AN ADVISORY COMMITTEE......
1. Matters Initially Referred to ACCS#1 – February 2011......
1.1Cefquinome......
1.2Derquantel......
1.3Diethylhexyl Phthalate......
1.4Emodepside......
1.5Flumioxazin......
1.6Mavacoxib......
1.7Metofluthrin......
1.8Proquinazid......
2. Matters Initially REferred to ACMS#2 – February 2011......
2.1.Proposed changes to Part 4 of the SUSMP (The Schedules)......
2.1.1Chloramphenicol......
2.1.2Fexofenadine......
2.1.3Ibuprofen......
2.1.4Ibuprofen combined with Paracetamol......
2.2.Proposed changes to Part 5 of the SUSMP (The Appendices)......
2.2.1Asenapine......
2.2.2Pantoprazole......
2.2.3Rupatadine......
2.2.4Tafluprost......
2.2.5Tapentadol......
2.2.6Tolvaptan......
3. Matters Initially Referred to aCCS-ACMS#2 – February 2011......
3.1Methylsulfonylmethane / Dimethyl Sulfone......
PART B – FInal Decisions on Matters Not REFERRED TO AN ADVISORY COMMITTEE......
4. Chemicals......
4.1Bispyribac......
4.2Toceranib......
5. Medicines......
5.1Apixaban......
5.2Canakinumab......
5.3Eculizumab......
5.4Fingolimod......
5.5Ticagrelor......
5.6Vernakalant......
6. Editorials and Errata......
GLOSSARY
ABBREVIATIONNAME
AANAustralian Approved Name
ACActive Constituent
ACCCAustralian Competition and Consumer Commission
ACCMAdvisory Committee on Complementary Medicines (formerly Complementary Medicine Evaluation Committee [CMEC])
ACNPMAdvisory Committee on Non-Prescription Medicines (formerly Medicines Evaluation Committee [MEC])
ACPMAdvisory Committee on Prescription Medicines (formerly Australian Drug Evaluation Committee [ADEC])
ACSMAdvisory Committee on the Safety of Medicines (formerly Adverse Drug Reactions Advisory Committee [ADRAC])
ADECAustralian Drug Evaluation Committee (now Advisory Committee on Prescription Medicines [ACPM])
ADIAcceptable Daily Intake
ADRACAdverse Drug Reactions Advisory Committee (now Advisory Committee on the Safety of Medicines [ACSM])
AHMACAustralian Health Ministers' Advisory Council
APVMAAustralian Pesticides and Veterinary Medicines Authority
AQISAustralian Quarantine and Inspection Service
ARfDAcute Reference Dose
ASCCAustralian Safety and Compensation Council
ASMIAustralian Self-Medication Industry
ARTGAustralian Register of Therapeutic Goods
CASChemical Abstract Service
CHCComplementary Healthcare Council of Australia
CMECComplementary Medicine Evaluation Committee (now Advisory Committee on Complementary Medicines [ACCM])
CMIConsumer Medicine Information
COAGCouncils Of Australian Governments
CRCChild-Resistant Closure
CTFAACosmetic, Toiletry & Fragrance Association of Australia
ECRPExisting Chemicals Review Program
EPAEnvironment Protection Authority
ERMAEnvironmental Risk Management Authority (NZ)
FAISDFirst Aid Instructions and Safety Directions
FDAFood and Drug Administration (US)
FOIFreedom of Information Act 1982
FSANZFood Standards AustraliaNew Zealand
GHSGlobally Harmonised System for Classification and Labelling of Chemicals.
GITGastro-intestinal tract
GPGeneral Practitioner
HCNHealth Communication Network
HCPHealth Care Provider
INNInternational Non-proprietary Name
ISOInternational Standards Organization
LC50The concentration of a substance that produces death in 50% of a population of experimental organisms. Usually expressed as mg per litre (mg/L) as a concentration in air.
LD50The concentration of a substance that produces death in 50% of a population of experimental organisms. Usually expressed as milligrams per kilogram (mg/kg) of body weight
LOAELLowest Observed Adverse Effect Level
LOELLowest Observed Effect Level
MCCMedicines Classification Committee (NZ)
MECMedicines Evaluation Committee (now Advisory Committee on Non-Prescription Medicines [ACNPM])
MOHMinistry of Health (NZ)
NCCTGNational Coordinating Committee of Therapeutic Goods
NDPSCNational Drugs and Poisons Schedule Committee
NHMRCNational Health and Medical Research Council
NICNASNational Industrial Chemicals Notification & Assessment Scheme
NOAECNo Observed Adverse Effect Concentration
NOAELNo Observed Adverse Effect Level
NOELNo Observable Effect Level
NOHSCNational Occupational Health & Safety Commission
OCMOffice of Complementary Medicines
OCSEHOffice of Chemical Safety and Environmental Health
ODAOffice of Devices Authorisation
OMAOffice of Medicines Authorisation (was Office of Prescription and Non-prescription Medicines)
OOSOut of Session
OTCOver-the-Counter
PACIAPlastics And Chemicals Industries Association
PARPrescription Animal Remedy
PBACPharmaceutical Benefits Advisory Committee
PECPriority Existing Chemical
PGAPharmaceutical Guild of Australia
PHARMPharmaceutical Health and Rational Use of Medicines
PIProduct Information
PICPoisons Information Centre
PSAPharmaceutical Society of Australia
QCPPQuality Care Pharmacy Program
QUMQuality Use of Medicines
RFIRestricted Flow Insert
SCCNFPScientific Committee on Cosmetic and Non-Food Products
SCCPScientific Committee on Consumer Products
STANZHAStates and Territories and New Zealand Health Authorities
SUSDPStandard for the Uniform Scheduling of Drugs and Poisons
SUSMPStandard for the Uniform Scheduling of Medicines and Poisons
SVTFirst aid for the solvent prevails
TCMTraditional Chinese Medicine
TGATherapeutic Goods Administration
TGCTherapeutic Goods Committee
TGOTherapeutic Goods Order
TTHWPTrans-Tasman Harmonisation Working Party
TTMRATrans-Tasman Mutual Recognition Agreement
WHOWorld Health Organization
WPWorking Party
WSWarning statement
Delegates’ reasons for final decisions
June 20111
PART A – FInal Decisions on Matters REFERRED TO AN ADVISORY COMMITTEE
1. Matters Initially Referred to ACCS#1 – February 2011
1.1Cefquinome
DELEGATE’S REFERRAL TO EXPERT ADVISORY COMMITTEE
The delegate considered the scheduling of cefquinome and decided to seek advice from the ACCS on the following:
Cefquinome – proposal to include cefquinome in Schedule 4.
EXPERT ADVISORY COMMITTEE RECOMMENDATION
The Committee recommended that a new Schedule 4 entry be created for cefquinome. The Committee also recommended an implementation date of no more than 6 months after the delegate’s final decision.
BACKGROUND
Currently the SUSMP prefers the use of sulfate rather than sulphate.
Cefquinome sulfate belongs to the cephalosporin group of antibiotics which act by inhibition of cell wall synthesis, resulting in bacterial cell death. The structure is:
XXXXX has submitted data to the Australian Pesticides and Veterinary Medicines Authority (APVMA) seeking the approval of a new active ingredient, cefquinome sulfate, and the registration of XXXXX.
XXXXXRisk Assessment Technical Report on XXXXX APVMA submission included a scheduling recommendation for cefquinome sulfate. A delegate agreed that this was a matter for a scheduling consideration and that advice from the ACCS was needed.
SCHEDULING STATUS
Cefquinome is not specifically scheduled. It would, however, be captured by the Schedule 4 group entry for antibiotic substances.
INITIAL SUBMISSIONS
Applicant’s Submission
The XXXXX Risk Assessment Technical Reportconcluded that, based on the toxicity profile of cefquinome sulfate and the need for veterinary diagnosis of the indicated condition XXXXX, cefquinome sulfate should be included in Schedule 4.
Other XXXXX conclusions included:
- There were no objections on human health grounds to the approval of the active ingredient cefquinome sulfate or to the registration of the product.
- As the product was an antibiotic and not intended to be used in food-producing animals, establishment of an ADI and ARfD for cefquinome sulfate was not required. If cefquinome sulfate were to be used in the future to treat food producing animals, a microbial ADI and/or toxicological ADI would have to be established.
- XXXXX.
- No re-entry, re-handling, warning or precautionary statements were required.
Members noted that the applicant submitted studies to the APVMA on toxicokinetics and metabolism, acute toxicity, subchronic toxicity, genotoxicity, developmental and reproductive toxicity. Although most studies did not strictly conform to current test guidelines or standards of reporting, they were considered acceptable by the evaluator for the assessment of the toxicology profile of cefquinome sulfate in this case.
Toxicology
Members noted the following toxicology summary for cefquinome sulfate:
XXXXX
- Cefquinome sulfate had low acute oral toxicity XXXXX, low acute intravenous XXXXX and subcutaneous toxicity XXXXX.
- Cefquinome sulfate was not a skin sensitiser in XXXXX. No acute inhalation toxicity, skin or eye irritation studies were provided. However, based on the use pattern of the product, exposure by these routes was likely to be minimal.
- Repeat-dose oral toxicity studies were performed in XXXXX. The main toxicological effect noted in XXXXX was increased kidney weight and changes in clinical chemistry and urinalysis parameters suggestive of an alteration in renal function, as well as vacuolisation of the epithelial cells of the convoluted proximal tubules of the kidney. Enlargement of the caecum was also seen but without corroborative histological findings. This was likely due to changes in the intestinal microflora, which is a side effect common to cephalosporin antibiotics. In XXXXX, interference with hepatic synthesis of certain molecules such as cholesterol and triglycerides was observed, and liver weights were increased without corroborative histological findings.
- In a XXXXX reproduction study, there were no effects on reproductive parameters, and cefquinome sulfate was not a developmental toxicant XXXXX developmental toxicity study. Studies on carcinogenicity were not provided, however, cefquinome sulfate was not mutagenic or genotoxic in in vitro studies, or genotoxic in an in vivo study.
Members additionally noted the results of a study designed to determine the minimum inhibitory concentration of cefquinome sulfate against a range of bacteria genera and strains that were representative of the human colonic microflora, bacterial suspensions were inoculated into agar plates at two different densities. No strain was sensitive to cefquinome at concentrations below XXXXX. The most sensitive species was XXXXX.
Members noted that no toxicity studies were submitted for the product. The acute oral and dermal toxicity was estimated from the available toxicity data on the active constituent and other constituents as summarised below:
Toxicity end point / Toxicity of ProductOral / Low
Dermal / Low
Inhalational / No data
Skin irritation / No data
Eye irritation / No data
Skin sensitisation / Unlikely
Use Pattern / Exposure
Members noted the following summary of use pattern and exposure information from the XXXXX report:
- XXXXX.
- The product would be administered by qualified veterinarians and trained farmers, so any potential for exposure will be restricted to these trained individuals who would be aware of the possible toxicity associated with the product.
- XXXXX.
Hazard Classification
Cefquinome is not listed on Safe Work Australia’s Hazardous Substances Information System (HSIS) Database. The XXXXX has determined that both cefquinome sulfate and the product are not classified as a hazardous substance according to NOHSC Approved Criteria for Classifying Hazardous Substances.
Applicant’s Response to the Evaluation Report
XXXXXhad considered the XXXXXReport, including the scheduling recommendation, and advised that there were no comments.
February 2011 Pre-meeting Submissions
No pre-meeting submissions were received.
EXPERT ADVISORY COMMITTEE DISCUSSION
Members generally agreed that relevant matters under Section 52E (1) included (a) risks and benefits; and (b) the purpose and extent of use.
Members noted that as cefquinome sulfate was an antibiotic substance it was already captured by Schedule 4. Members also agreed that there was no information to suggest that anything other than supply by prescription should apply to the availability of cefquinome sulfate. For clarity, Members agreed that a separate specific listing in Schedule 4 would be appropriate.
Members then discussed the wording of a specific Schedule 4 entry. Members noted the precedent for schedulinga parent substance rather than a specific salt unless the salt has unique toxicity. Members agreed that there were no data to indicate unique toxicity and a parent entry for cefquinome was considered to be sufficient. A Member also suggested limiting the specific entry to animal use only, on the presumption that the group entry for antibiotic substances would still capture any potential human use. Other Members clarified that the group entry would not apply if there was a specific entry i.e. limiting the cefquinome entry to animal use would mean that cefquinome for any other use, including human use, would then be unscheduled. A Member particularly raised the concern that inappropriate access through importation for personal human use could occur if such use were not classed as Schedule 4. The Committee agreed that the specific entry needed to remain broad to capture all potential uses of cefquinome.
A Member noted that there had been considerable controversy overseas, particularly in the US, over the use of cefquinome in animals. Cefquinome is a 4th generation cephalosporin and the Member had concerns about the use of a 4th generationantibiotic in animals as this could potentially lead to increases in antibiotic resistance. Members noted advice that the APVMA would investigate these claims, noting that the cost of this antibiotic was likely to mitigate any propensity for misuse or abuse. Members noted that while this was an issue that APVMA was aware of, it was yet another reason for cefquinome to be Schedule 4.
DELEGATE’S INTERIM DISCUSSION
The delegate concluded that the recommendations of the ACCS were clear and appropriately supported. The delegate agreed with these recommendations.
The delegate agreed that the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989 included (a) risks and benefits and (b) the purpose and extent of use.
DELEGATE’S INTERIM DECISION
The delegate decided to include cefquinome in Schedule 4. The delegate decided that an implementation date of 1 January 2012 was appropriate (i.e. six months after publication of the final decision).
SUBMISSIONS ON INTERIM DECISION
No submissions were received on the interim decision.
DELEGATE’S FINAL DECISION
The delegate confirmed that cefquinome be included in Schedule 4. The delegate also confirmed an implementation date of 1 January 2012.
Schedule 4 – New entry
CEFQUINOME.
1.2Derquantel
DELEGATE’S REFERRAL TO EXPERT ADVISORY COMMITTEE
The delegate considered the scheduling of derquantel and decided to seek advice from the ACCS on the following:
Derquantel – proposal to include derquantel in Schedule 6 with a cut-off to Schedule5 for preparations containing 1 per cent or less of derquantel.
EXPERT ADVISORY COMMITTEE RECOMMENDATION
The Committee recommended that a new Schedule 6 entry be created for derquantel, with a cut-off to Schedule 5 for preparations containing 1 per cent or less of derquantel. The Committee also recommended an implementation date of no more than six months after the delegate’s final decision.
BACKGROUND
Derquantel is a member of the spiroindole class of anthelmintics. It acts as a selective nicotinic antagonist in somatic muscle by competing for the ganglionic nicotinic cholinergic receptors, thus inducing flaccid paralysis in parasitic nematodes. Its structure is:
XXXXX.
XXXXX has submitted data to the Australian Pesticides and Veterinary Medicines Authority (APVMA) seeking approval for the active ingredient derquantel and the registration of XXXXX.
The XXXXX Risk Assessment Technical Report on XXXXX APVMA submission included a scheduling recommendation for derquantel. The delegate agreed that this was a matter for a scheduling consideration and that advice from the ACCS was needed.
SCHEDULING STATUS
Derquantel is not currently scheduled.
INITIAL SUBMISSIONS
Applicant’s Submission
The XXXXXReportfound that derquantel presents a hazard for repeated use, and although it is considered unlikely to produce irreversible toxicity it is a competitive nicotinic antagonist that has produced clinical signs of neurotoxicity in XXXXX. Thus, the evaluator concluded that derquantel met the requirements of a Schedule 6 chemical. The evaluator recommended that derquantel be included in Schedule 6 with a 1 per cent cut-off to Schedule 5.
Other XXXXX conclusions included:
- There were no objections on human health grounds to the approval of active ingredient derquantel XXXXX.
- The ADI for derquantel was established at 0.0005 mg/kg bw/d based on a LOEL of 0.1 mg/kg bw/d in a XXXXX and using a 200-fold safety factor.
- The ARfD for derquantel was established at 0.01 mg/kg bw based on a NOEL of 1 mg/kg bw in an XXXXX and using a 100-fold safety factor.
- Recommended labelling included the safety directions “May irritate the skin” and “Avoid contact with the skin”. Members noted, however, that Appendices E and F do not apply to products regulated by the APVMA. APVMA sets these labelling requirements as part of its product approval process.
- No re-entry, re-handling, warning or precautionary statements are required.
Members also noted the following further information regarding derquantel’s mode of action in mammals: