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Scheduling delegate's final decisions: ACCS/ACMS, June 2013

Scheduling medicines and poisons

28 June 2013

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Part A: Scheduling proposals referred to the March 2013 joint meeting of the ACCS and ACMS

3.1 Adrenaline, Bupivacaine and Lignocaine

Scheduling proposal

The Chemicals Scheduling Delegate and the Medicines Scheduling Delegate (the delegates) considered a proposal to reschedule a veterinary preparation containing adrenaline, bupivacaine and lignocaine from Schedule 4 to Schedule 6 in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP).

The delegates referred the proposal to the Advisory Committee on Chemicals Scheduling (ACCS) and the Advisory Committee on Medicines Scheduling (ACMS) for advice.

Adrenaline, bupivacaine and lignocaine are listed in Schedule 4. Adrenaline and lignocaine, apart from the listing in Schedule 4, are also listed in Schedules 3 and 2 respectively.

Scheduling history

Adrenaline

In January 1955, the Poisons Schedules Committee (PSC) listed adrenaline in Schedules 2 and 3 for preparations of less than 1 per cent and in Schedule 4 for preparations containing more than 1 per cent.

In May 1956, the PSC decided that the Schedule 2 entry was deleted and the Schedule 3 entry refined to exempt concentrations of less than 0.01 per cent.

In August 1985, the PSC decided to amend the Schedule 3 and 4 entries for adrenaline to raise the exemption to preparations containing 0.02 per cent, stating that such a low level is not toxic and does not pose a health risk except in diabetics.

In February 1999, the National Drugs and Poisons Schedule Committee (NDPSC) recommended that New Zealand harmonise with the Australian adrenaline scheduling. New Zealand subsequently agreed to this recommendation.

In February 2010, the NDPSC considered an application to include adrenaline auto-injector in Appendix H entry. The NDPSC agreed that auto-injectors were included in Schedule 3 to facilitate emergency access for a specific group of people rather than the usual purpose of the majority of Schedule 3 listings i.e. to provide the community with access to a beneficial therapeutic option which requires professional advice but not a prescription. The NDPSC agreed that it was concerned that advertising could undermine this distinction. The NDPSC decided that the inclusion of adrenaline in Appendix H was inappropriate.

Bupivacaine

In 1983 August, the PSC decided to include bupivacaine in Schedule 4 of the SUSMP.

Lignocaine

In February 1998, the NDPSC considered a submission for rescheduling of dermal preparations containing 1 per cent or less of lignocaine in packs of 30 g or less, from Schedule 2 to unscheduled. The NDPSC decided that based on the use pattern at that time, it did not wish to amend the scheduling of lignocaine.

In May 1998, following its reconsideration of the applicant's comments, and subsequent examination of public comments, the NDPSC decided that it did not wish to change the decision of the February 1998 Meeting and that lignocaine would remain a scheduled substance.

In October 2008, the NDPSC considered a proposal to broaden the current Schedule 2 exemption for dermal use (less than or equal to 2 per cent) to also exempt use on gums.

At that time the NDPSC decided that the current Scheduling remained appropriate.

The Trans-Tasman Harmonisation Working Party recommended that 2 per cent lignocaine or less in dermal preparations should be exempted from scheduling. This recommendation was adopted at the February 2001 NDPSC Meeting.

Public pre-meeting submissions

Five public submissions (including a late submission) were received.

Two submissions (both have identical contents) indicated that inclusion of these substances in Schedule 6 could potentially lead to an increase in adoption of the use of these substances for mulesing, ultimately leading to improve welfare outcomes for lambs undergoing mulesing. These two submissions supported the scheduling proposal to reschedule these substances.

One submission indicated that it supported the rescheduling of adrenaline and lignocaine. The submission did not provide comments on bupivacaine.

One submission indicated that rescheduling these substances would potentially leads to misuse, including for treating castration wounds and injuries, therefore did not support the delegates' proposal.

One late public submission indicated that it did not oppose the delegates' rescheduling proposal, provided it does not result in Tri-solfen no longer being available to woolgrowers for the purpose of alleviating the pain associated with the mulesing procedure and as long as the scheduling requirements ensure that the product continues to be used in the manner intended and described on the product label.

The redacted public submissions are available at Public submissions on scheduling matters referred to ACCS #7, ACMS #8 and the joint ACCS-ACMS #5 (March 2013).

Advisory Committee on Chemicals Scheduling (ACCS) and the Advisory Committee On Medicines Scheduling (ACMS) advice to the delegates

The joint ACCS & ACMS Committee recommends that the current scheduling of adrenaline, bupivacaine and lignocaine remains appropriate.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the Committee included; (a) the risks and benefits of the use of a substance, (c) the toxicity of a substance and (d) the dosage, formulation, labelling, packaging and presentation of a substance.

The following reasons were noted:

  • insufficient data available to demonstrate that a change in Schedule will result in wider appropriate usage versus wider inappropriate usage.
  • as mulesing is a regulated process, there is no evidence that rescheduling would improve the extent of use.
  • rescheduling would increase the risk of the product being inappropriately used.
  • rescheduling would increase the likelihood of larger quantities being available which could lead to misuse.

Delegates interim decision

The delegates considered, and accepted, the advice of the joint ACCS & ACMS, advising that the specific uses of the veterinary product for pain relief in the practice of 'mulesing' sheep require veterinary supervision, and that changes to the existing Schedule 4 entries of the three active ingredients are not warranted. Accordingly, no scheduling changes are proposed in making an interim decision.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the Committee included; (b) the purpose, (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.

The following reasons were noted:

  • as mulesing is a regulated process, there is no evidence that rescheduling would improve the extent of use.
  • the toxicity of the local anaesthetic ingredients and the relatively narrow window of effectiveness in pain relief associated with mulesing, warrant appropriate supervision of treatment by a veterinarian.
  • rescheduling to Schedule 6 could result in the product, currently available in 100 ml injection vials, being made available in much larger bulk containers, increasing the risk of inappropriate use.
  • rescheduling from Schedule 4 to Schedule 6 could increase the risk of the product being inappropriately used for purposes other than pair relief after mulesing.
  • a broadening of use in pain relief for the practice of mulesing is a desirable outcome, but this can be achieved within existing scheduling arrangements, especially via advertising, which would remain restricted to professional journals and related sources.

Submissions on interim decision

Six submissions were received. Only one of the submissions was a valid submission. Other submissions were submissions from parties other than those who made a valid submission in response to the original invitation or the applicant.

Two submissions indicated that mulesing does not require diagnosis or the attendance of a veterinarian. The product containing substances alleviate pain in lambs undergoing mulesing and this process does not require direct (on farm) veterinary supervision or monitoring. The submissions therefore support the applicant's proposal to rescheduling of the substances in the product.

One submission indicated that under the Victorian Drugs and Poisons Controlled Substances Regulation, before dispensing a product the veterinary practitioner must ensure that the drug or poison is for the treatment of an animal under the veterinarian's care. Most private veterinary practitioners rarely visit commercial sheep farm. The submission noted that it would be advantageous from an animal ethics view point if all mulesed lambs were treated with this product. This could be achieved if the product was not listed in Schedule 4 and could be advertised more generally.

One submission noted that move to make the product containing these substances more readily available to woolgrowers is likely to result in an improved animal health outcome.

Two submissions noted that for those lambs that require the mulesing procedure, the use of the product as a post-operative analgesic provides the best welfare outcome currently available to producers. Adoption of practices to support sheep welfare is of critical importance to the sustainability of the Australian wool-production industry. The submissions noted that the proposed scheduling change would result in a significant increase in use of the product for its intended purpose by improving its availability to sheep producers and allowing the direct promotion of the product to end-users. The submissions indicated that the preparations for mulesing that contain adrenaline, bupivacaine and lignocaine be listed in Schedule 6.

The redacted public submissions are available at Public submissions on scheduling matters.

Delegate's consideration

The delegate considered the following in regards to this proposal:

  • scheduling proposal;
  • ACCS & ACMS advice;
  • section 52E of the Therapeutic Goods Act 1989;
  • scheduling factors13;
  • public submissions; and
  • other relevant information.

Delegate's final decision

The delegates have considered the submissions received following publication of the interim decision to retain Schedule 4 status for this product, in addition to a further review of the initial submissions and the advice from the ACCS & ACMS. On the basis of this review, the delegates have decided to set aside the interim decision, and institute scheduling changes that would allow the specific product under consideration to be re-scheduled to Schedule 5.

The proposed implementation date for this decision is 1 February 2014.

Other reasons

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegates included; (a) the risks and benefits of the use of the substance, (b) the purpose, (c) the toxicity of a substance, (d) the dosage, formulation, labelling, packaging and presentation of a substance, and (e) the potential for abuse.

The principal reason behind the interim decision to retain the two local anaesthetic active ingredients lignocaine and bupivacaine) in Schedule 4 was advice tendered by the ACCS & ACMS and in the Australian Pesticides and Veterinary Medicines Authority (APVMA) submission, that 'mulesing' is a procedure that should be carried out under the supervision of a veterinarian. This was alleged to be necessary to ensure appropriate treatment, including observance of the 90-day withholding period prior to slaughter for meat consumption. This advice further contended that re-scheduling from Schedule 4 could lead to inappropriate use (for treatment of wounds other than those associated with 'mulesing') and an increase in the availability of the product in larger containers.

All these points were effectively rebutted in the post-decision submissions, one of which came from the original applicant, one from the product developer, one from the product registrant, and three from agricultural and woolgrowing authorities. In particular, the delegates now note that information about the product being supplied in 100mL containers is erroneous, and that it is currently available in containers from 1 to 22L in size. In relation to main points raised in the submissions, the delegates are now of the opinion that the requirement for veterinary intervention and/or supervision is not needed for the proper conduct of 'mulesing'. The evidence tendered suggests that the current practice, with farmers and contractors using the product without direct veterinary supervision has been working well, with no evidence of inappropriate use. Furthermore, the delegates accept the contention that a requirement for veterinary prescription can place an undue burden on farmers and contractors working in areas remote from the availability of veterinary practices. Re-scheduling would be reasonably expected to result in an improvement in animal welfare, with more sheep being treated to reduce pain and infection than would otherwise have been left untreated.

The issue then becomes what scheduling change best meets this objective. The original and supporting submissions propose re-scheduling to Schedule 6, on the 'cascading' principle of easing schedule requirements, although there was some comment that Schedule 5 could also be an appropriate level of scheduling. In 1994-96, the then NDPSC considered the issue of whether the active components of veterinary medicines included in Schedule 6 should be re-scheduled, where possible, to Schedule 5. This was driven by a concern that medicines intended for the oral treatment of animals could be inappropriately labelled with the signal heading POISON, rather than the previously available signal heading of CAUTION. A number of veterinary medicines were re-scheduled to Schedule 5 where their toxicity profiles had been re-evaluated, including consideration of the likelihood that a child could reasonably be exposed to a fatal dose.

The product currently under consideration for re-scheduling contains lignocaine (4.06 per cent) and bupivacaine (0.42 per cent). At these dilutions, the acute toxicity profile is reasonably consistent with the Scheduling Policy Framework guidelines for listing in Schedule 5. Furthermore, the product label includes appropriate warning statements and safety directions to ensure that users are warned of the potential risks. It is also noted that lignocaine is available 'over-the-counter in pharmacies' (Schedule 2) in topical human medicines at concentrations up to 10 per cent, with exemption from scheduling at 2 per cent. This further reinforces the view that a POISON signal heading for a product intended for topical application with twice the exempt concentration of lignocaine appears to be unnecessary.

The other active ingredients in the product are adrenaline (0.0025 per cent) and the quaternary ammonium antiseptic (cetrimide 0.5 per cent). At these concentrations, both components are exempt from scheduling, and no adjustment needs to be made to their current SUSMP entries.

The delegates note that, currently, the APVMA has registered only one veterinary product containing bupivacaine while there are 14 products containing lignocaine (mostly in Schedule 4). It is therefore important that the re-scheduling of these actives to Schedule 5 should apply only to the particular product and its use in 'mulesing'.

Schedule entry

Schedule 4 - Amendment

BUPIVACAINE except when included in Schedule 5.

Schedule 5 - New entry

BUPIVACAINE in aqueous gel preparations containing 0.5 per cent or less of bupivacaine, for the dermal spray-on treatment of wounds associated with 'mulesing' of sheep.

Schedule 4 - Amendment

LIGNOCAINE except:

  • (a) when included in Schedules 2 or 5;
  • (b) in dermal preparations containing 2 per cent or less of total local anaesthetic substances per dosage unit; or
  • (c) in lozenges containing 30 mg or less of total anaesthetic substances per dosage unit
Schedule 5 - New entry

LIGNOCAINE in aqueous gel preparations containing 4.5 per cent or less of lignocaine, for the dermal spray-on treatment of wounds associated with 'mulesing' of sheep.

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3.2 Tylosin

Scheduling proposal

The Chemicals Scheduling Delegate and the Medicines Scheduling Delegate (the delegates) considered a proposal to reschedule tylosin from Schedule 5 to Schedule 4 in the Standard for the Uniform Scheduling of Medicines and Poisons.

The delegates referred the proposal to the Advisory Committee on Chemicals Scheduling (ACCS) and the Advisory Committee on Medicines Scheduling (ACMS) for advice.

Scheduling status

Tylosin is listed in Schedules 4 and 5.

Tylosin is a macrolide antimicrobial agent approved in Australia by the APVMA for use in poultry, pigs and cattle. As of March 2013, tylosin is available as an injection, water-soluble antimicrobial preparation and as premix. While injectable and water-soluble formulations are in Schedule 4 (Prescription Animal Remedy), the feed premix formulations are, according to the concentration of tylosin in the marketed premix, either in Schedule 4 or in Schedule 5 (available over-the-counter without a prescription).

Scheduling history

In November 1968, the then Poisons Schedule Sub-Committee (PSSC) recommended that an entry group 'antibiotics' be included in Schedule 4 except when tylosin and other macrolides bacitracin, erythromycin and oleandomycin when added to animal feedstuffs for the purpose of growth promotion in concentrations not exceeding 50 ppm, which should be exempt from scheduling. Antibiotic premixes for growth promotion purposes containing the antibiotics above in concentrations greater than 50 ppm but not in excess of 20,000 ppm should be exempt from Schedule 4 when packed and labelled in accordance with Schedule 6 of the Uniform Poisons Schedules. Water soluble antibiotic preparations intended for addition to animals' drinking water should not be made available without prescription.

In May 1977, the then Poisons Schedule Committee (PSC) decided to amend the Schedule 4 entry for antibiotics to include animal feedstuffs containing bacitracin, erythromycin, oleandomycin, tylosin and virginiamycin in concentration of 50 ppm or less of the total active antibiotic principles. The PSC was of the opinion that the continued use of antibiotics as growth promotions in animal feedstuffs could lead to an impairment of their efficacy in the treatment of human disease.

In May 1978 specific entries for antibiotics including tylosin, bacitracin, erythromycin, oleandomycin and virginiamycin were included in Schedule 4, except in animal feedstuffs for growth promotion in concentrations of 50 mg / kg or less of the total active antibiotic principle (remained Schedule 6).

In November 1986, the then Drugs and Poisons Schedule Standing Committee (DPSSC) considered a submission to remove tylosin from Schedule 4 to Schedule 6. The review noted that if the concentration of tylosin in the premix was increased it would increase the chance of erythromycin resistance occurring in possible human pathogens. The DPSSC decided not to remove the Schedule 4 entry and recommended the Schedule 6 level of tylosin in premixes be increased from 2 to 5 per cent.

In November 1990, the DPSC considered an apparent anomaly in the scheduling of tylosin. The DPSC confirmed the current scheduling that the Schedule 4 entry related to uses involving therapeutic claims while Schedule 6 entry was solely for growth promotion purposes.

In May 1993, the DPSC decided to include safety directions for a Schedule 6 tylosin stockfeed premix.

In February 1996, the National Drugs and Poisons Schedule Committee (NDPSC) decided to reschedule tylosin from Schedule 6 to Schedule 5. The NDPSC considered that the registered products for oral use fell within the acute oral criteria of the new draft guidelines for Schedule 5 and recommended that tylosin when in veterinary products for oral use should be classified as Schedule 5.

In 1999, the Joint Expert Technical Advisory Committee on Antibiotic Resistance (JETACAR) recommended "that all antibiotics for use in humans and animals (including fish) be classified as Schedule 4 (prescription only)." The JETACAR report also recommended that a review of the macrolides (tylosin, kitasamycin, oleandomycin) be undertaken as a priority to assess efficacy and to ensure that continued use is "not likely to impair the efficacy of any other prescribed therapeutic antibiotic or antibiotics for animal or human infections through the development of resistant strains of organisms".

In February 2003, the NDPSC scheduled / rescheduled all antibiotics (except tylosin, kitasamycin, oleandomycin) for use in human and animals in Schedule 4: viginiamycin, bacitracin, cuprimyxin, erythromycin, hygromycin, nalidixic acid, nisin, spiramycin and avoparcin as part of its response to the recommendations (in 1999) of the JETACAR.

The October 2003 NDPSC meeting considered a letter sent to feed mill sales representatives from XXXXX in which the company highlighted the Committee's decision regarding the rescheduling of virginiamycin to Schedule 4. XXXXX letter mentioned that XXXXX (containing tylosin) remained in Schedule 5 and was unaffected by the NDPSC decision. The NDPSC agreed to refer claims of inappropriate promotion of antibiotics that are yet to be reviewed under JETACAR to Expert Advisory Group on Antimicrobial Resistance (EAGAR) and the APVMA.

In June 2012, the joint Committee considered a referral from the medicines and chemicals scheduling delegates to consolidate the scheduling of all uses of tylosin in Schedule 4. The joint Committee agreed that they were unable to provide the scheduling delegates informed advice at that stage. The delegates noted that the APVMA review on macrolides was yet to be completed. The delegates therefore decided not to make a scheduling decision on this issue and referred this matter to the March 2013 joint Committee meeting for advice.

Public pre-meeting submissions

Five public submissions were received.

Two submissions supported the delegates' proposal to reschedule tylosin from Schedule 5 to Schedule 4.

One submission requested that if tylosin is included in Schedule 4, implementation time be extended to deplete the products containing tylosin currently available on the market.

One submission indicated that if tylosin is included in Schedule 4, other antibiotics with greater risk profiles for antimicrobial resistance would need to be used. The Schedule 4 listing of tylosin would also increase the cost due to the requirement of a veterinarian consultation.

One submission suggested that the delegates continue to defer the tylosin rescheduling decision until various issues, including the senate review, are resolved.

The redacted public submissions are available at Public submissions on scheduling matters.

Advisory committee on chemicals scheduling (ACCS) advice to the delegate

The ACCS & ACMS considered the referral from the scheduling delegates to reschedule tylosin from Schedule 5 to Schedule 4 in the Standard for the Uniform Scheduling of Medicines and Poisons. The Committees advised the delegates that it was unable to make a scheduling recommendation or to provide advice at this time due to lack of provision to the Committees of all of the available data in the form of the macrolide review or an alternative acceptable process.

Delegates interim decision

The delegates have decided to defer making an interim decision on the consolidation of the scheduling of tylosin in to Schedule 4, pending receipt of further advice on the key issue of the risks of expanding antibiotic resistance associated with its use as an animal health feed additive (the current Schedule 5 and exempt uses).

Submissions on interim decision

No public submissions were received.

Delegate's consideration

The delegate considered the following in regards to this proposal:

  • evaluation report (not publically available);
  • scheduling proposal;
  • ACCS & ACMS advice;
  • section 52E of the Therapeutic Goods Act 1989;
  • scheduling factors14;
  • public submissions (pre-meeting); and
  • other relevant information.

Delegate final decision

The delegates have confirmed the interim decision to defer making any schedule change, pending receipt of further information. The delegates have confirmed that the reasons for deferral of a scheduling decision are in keeping with those for the interim decision.

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3.3 Terminology

Scheduling proposal

The chemicals scheduling delegate and the medicines scheduling delegate (the delegates) considered a proposal to include terms, such as synthetic, analogue and derivative, to the Part 1, Introduction in order to better define these terms, their intent and purpose in the Standard for the Uniform Scheduling of Medicines and Poisons.

The delegates referred the proposal to the joint ACCS & ACMS for advice.

Scheduling history of synthetic cannabinoids

In July 2011, the Medicines Scheduling Delegate decided to include eight specific synthetic cannabis-like substances in Schedule 9.

In February 2012, the Medicines Scheduling Delegate decided to include another nine specific synthetic cannabis-like substances in Schedule 9.

Scheduling status of synthetic cannabinoids

There are several synthetic cannabinoids currently specifically listed in Schedule 4 (e.g. rimonabant), Schedule 8 (e.g. nabilone) and Schedule 9 (e.g. JWH-018). These entries also capture a number of other synthetic cannabinoids as derivatives in accordance with Part 1 (2) of the SUSMP.

Public pre-meeting submissions

Three public submissions were received.

A submission indicated that the current understanding of "analogue" and "derivative" encompasses "ethers, esters, and salts" and indicated that this definition may be too broad. The submission suggested that stereoisomers and salts exhibiting no substantially different pharmacological properties (both pharmacokinetic and pharmacodynamic) from the parent molecule should be considered analogues or derivatives. The submission asserted that any broadening of this definition seems to run aground against intellectual patent law.

Two submissions indicated that the recent Drug Analogue workshop proposed that a new definition of a drug analogue should replace the existing definition in the Commonwealth Criminal Code Act 1995. One of the submission noted that it was intended that this new drug analogue definition should be used in its entirety either by inclusion into or by reference from the various Australian jurisdiction drug or poisons Acts. One of these submission also suggested that the current use of the term derivative in the context of the SUSMP includes a balanced consideration of the toxicology and pharmacology of a new drug, in addition to the chemical structure. The submission suggested that any adoption of a uniform analogue definition would potentially need to be complemented by a similar consideration of the toxicology and pharmacology aspects of new drugs.

The redacted public submissions are available at Public submissions on scheduling matters.

ACCS and ACMS advice to the delegate

The joint ACCS & ACMS Committee does not support the inclusion of the terms 'analogue', 'derivative' and 'synthetic' in Part 1, Interpretation, of the SUSMP.

Delegates' interim decision

The delegates considered the advice of the joint meeting of the ACCS & ACMS, advising that there is no support for including the terms 'analogue', 'derivative' and 'synthetic' in Part 1, Interpretation, of the SUSMP. The delegates noted from the discussion, that jurisdictions have been adequately served by the existing entries in Part 1. They have been able to effectively manage control over substances listed in Schedule 9, including the primary issue raised in the submission relating to interpretations involved in prosecutions. Therefore, the delegates determined that the requested changes (or clarifications) to definitions in Part 1 of the SUMSP are not warranted.

Submissions on interim decision

No submissions were received.

Delegate's consideration

The delegate considered the following in regards to this proposal:

  • scheduling application;
  • ACCS & ACMS advice;
  • section 52E of the Therapeutic Goods Act 1989;
  • scheduling factors15; and
  • other relevant information.

Delegate final decision

The delegates have confirmed the interim decision as no evidence has been received to alter the interim decision. The delegates have confirmed that the reasons for the final decision are in keeping with those for the interim decision.


Footnotes

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