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Submissions and TGA response: Draft OTC medicine monographs for topical imidazole antifungals, topical nasal decongestants and pholcodine

10 June 2014

The TGA would like to thank those in Australia and New Zealand who took the time to prepare a submission and provide helpful comments and suggestions in response to the consultation: Consultation: Draft OTC medicine monographs for topical imidazole antifungals, topical nasal decongestants and pholcodine. Discussions on these monographs were also held with Medsafe.

Submissions received

A total of four submissions were received.

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TGA response

Topical imidazole antifungals

One submission provided detailed recommendations and suggestions in relation to the draft monograph. These included changes to the indications so that the ARTG and label indications are consistent, inclusion of additional instructions and editorial suggestions.

Regulator's comments

Changes to the monographs have been made as a result of the comments received, as follows:

  • In the 'Introduction' section, the statement that the monograph does not apply to preparations for 'vaginal use' has been amended to refer to 'intra-vaginal use', to clarify that the monograph, which can apply to preparations for external genital thrush, does not apply to preparations for intra-vaginal use.
  • In the 'Directions for use' section, the statement "When indicated for nappy rash: Avoid use of baby wipes to cleanse the affected area as they may irritate the skin" has been added as an acceptable precaution.
  • Editorial changes have been made, incorporating some of the suggestions, for ease of reading and navigation.

In relation to the suggestion to change the Indications section so that the terminologies used in the ARTG and label indications are consistent, it should be noted that the intent was to have scientific indications in the ARTG indications and lay terms in the label indications.

Further, the suggestion to change the terms 'tinea or ringworm' to simply 'tinea', and 'tinea corporis' to 'tinea corporis (ringworm)', in the ARTG indications has not been applied given that ringworm and tinea are synonyms and tinea corporis is tinea/ringworm of the body. In addition, while the suggestion to use dot points in the ARTG indications is noted, this has not been adopted due to IT system constraints.

Following further consideration of the draft monograph, further changes and corrections have been made, as follows:

  • The words 'and help prevent reinfection' have been deleted from the directions for use for miconazole nitrate powder, consistent with the recommendation in ARGOM Appendix 5: Guidelines on OTC application for specific substances for antifungal agents for topical use, which states that "Prophylactic use of topical antifungal agents, including application to shoes or clothing, should be justified."
  • The warning statement "Consult your doctor or pharmacist before using this product if you are taking medicines to thin the blood (eg. warfarin or other anticoagulants)." has been deleted. This statement is only applicable to medicines containing miconazole for topical oral mucosal application and for vaginal use. This statement was inadvertently included in the draft monograph.
  • Changes to some of the wording and formatting to enhance clarity and consistency.

Outcome

The monograph has been revised and is now available on the OTC medicine monographs webpage for use in submitting N2 applications.

Topical nasal decongestants

One submission provided several recommendations or requests in relation to the draft monograph. These included addition of 'sinusitis' to the indications, tabulation of dosage, clarification regarding required advisory statements and removal of advisory statements considered to be not required or already included in the RASML or ARGOM, revision/clarification of limits for related substances and changes to wording and formatting throughout. A further submission requested clarification as to why limits for impurities had been specified and another submission also requested inclusion of 'sinusitis' in the indications and requested more clarity regarding mandatory labelling requirements.

Regulator's comments

Several changes have been made to the monograph as a result of the comments received, as follows:

  • 'Sinusitis' has been included in the indications, consistent with currently approved indications for these products.
  • Presentation of dosage in the monograph has been revised. Simple text, rather than tabulation of dosage, was considered preferable, particularly given that label size may be limited for these products. Tabulation of dosage on proposed labels would, however, still be acceptable as part of an N2 application, provided dosage was consistent with the monograph.
  • The advisory statement regarding use by only one person to prevent spread of infection has been changed from required to permitted and requirement for the pregnancy/breastfeeding advisory statement has been limited to the primary pack, consistent with ARGOM.
  • Required advisory statements are to be retained in the monograph at this stage, to provide clarity as to requirements. The advisory statements are required for all relevant topical nasal decongestant products, regardless of route of evaluation (N2 or other) and are reflective of the majority of past approvals. A proposal is underway to include the required statements in RASML. Once additional required statements have been captured in RASML, the monograph will be amended to simply refer to RASML requirements. Minor changes have been made to some advisory statements, in line with proposed new RASML statements.
  • A note has been added to clarify that currently the monograph includes all required advisory statements for the active ingredients, including those required by the RASML and ARGOM.
  • Following comments in relation to the proposed related substances limits, these limits have been further considered, historic application data has been further reviewed and the following changes have been made as a result:
    • Clarification has been included in the monograph as to the source of the limit for xylometazoline Impurity A (ie. from Xylometazoline Nasal Drops BP).
    • In the absence of guidance on oxymetazoline related substances from pharmacopoeial monographs, a 3% limit for oxymetazoline impurity A was initially specified in line with limits for the corresponding, structurally similar xylometazoline Impurity A. This limit has now been revised to 1.5%, based on further review of historic application data that indicates this to be a primary degradant with a previous maximum approved limit of 1.5% (and less in most cases).
    • The previous limit of 2% for total unspecified impurities (for all presentations) has been replaced by a limit of 3% for total impurities. This is consistent with the ARGOM guideline on related substances for well-established OTC medicines and with previously approved limits.
  • Changes have been made to wording and formatting to enhance clarity and consistency.

Outcomes

The monograph has been revised and is now available on the OTC medicine monographs webpage for use in submitting N2 applications.

Pholcodine

Three submissions provided recommendations and comments in relation to the draft monograph. These included deletion and/or clarification of the test for specific gravity from the finished product specifications as this was more an in-process control and also not a BP test; clarification on why a 2 mg/mL strength was not included in the monograph given that the BP included product monographs for both 1 and 2 mg/mL strengths, and noting the existence of alternative approved dosages for the 1 mg/mL strength.

Regulator's comments

Changes to the monographs have been made as a result of the comments received as well as further consideration, as follows:

  • Requirement for test and limit for specific gravity has been deleted.
  • Non-relevant references to USP General Chapter and TGO78 have been deleted.
  • A change to the additional instruction "If coughing worsens or does not go away after a few days, consult your doctor or pharmacist" has been made following further consideration of the draft monograph. This has been reworded to "If coughing persists or worsens, consult your doctor or pharmacist." This is because reference to 'if coughing does not go away after a few days' may be unrealistic given that acute cough due to viral upper respiratory tract infection such as in the common cold often lasts between 7-10 days. This is also reflective of past approvals. A proposal is underway to include the revised statement in RASML. Once this statement has been captured in RASML, the monograph can be amended to simply refer to RASML requirements.
  • 2 mg/mL strength and corresponding dosage instructions have been included in the monograph. It is noted that several 2 mg/ mL strength products have been approved by Medsafe in New Zealand.

The proposed 1 mg/mL dosage is to be retained. It is consistent with previous advice from the Medicines Evaluation Committee (MEC), the predecessor of the Advisory Committee of Nonprescription Medicines (ACNM), most Australian clinical reference texts and past approvals.

Outcomes

The monograph has been revised and is now available on the OTC medicine monographs webpage for use in submitting N2 applications.

Other issues

  • One submission recommended increased post market monitoring for products approved under the N2 application route.
  • One submission suggested that, where possible, monographs of the same medicine class be released simultaneously (eg. different cough suppressants) in order to minimise commercial advantage/disadvantage.

Regulator's comments

  • The TGA intends to undertake post market monitoring as outlined in the outcomes of the previous consultation on OTC Medicine Monographs.
  • Consideration has been given to grouping monographs of the same medicine class for simultaneous release (eg. analgesics in the first release). However, other factors such as likely demand for specific monographs and effort required for monograph development have impacted on prioritisation of monograph development, to the extent that such grouping has not been practical for the present round of release. However, the TGA will continue to consider this for future monograph releases.