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Submissions received: Draft OTC Medicine Monographs for Bromhexine hydrochloride; Dextromethorphan hydrobromide; Laxatives: Docusate sodium and/or sennosides; Hand sanitisers
The TGA would like to thank the respondents who made submissions in response to the Consultation: Draft OTC Medicine Monographs for Bromhexine hydrochloride; Dextromethorphan hydrobromide; Laxatives: Docusate sodium and/or sennosides and Hand sanitisers.
Four submissions were received. The following submissions provided consent for publication on the TGA website:
- Consultation submission: Accord Australasia (pdf,271kb)
- Consultation submission: Australian Self-Medication Industry (ASMI) (pdf,272kb)
- Consultation submission: Novapharm Research Australia Pty Ltd (pdf,182kb)
- Consultation submission: Anonymous (pdf,27kb)
Submission comments and TGA response
One respondent provided comments in relation to the draft monograph for Bromhexine hydrochloride.
The respondent questioned the origin of the dissolution method and the requirement for a dissolution test and considered that TGO78 instead requires a disintegration test.
In most cases the TGA would expect inclusion of a dissolution test for oral solid dose forms rather than a disintegration test. Previously approved bromhexine tablets have included test/limits for dissolution rather than a disintegration test.
In the absence of pharmacopoeial guidance, the proposed dissolution test and limits in the monograph were based on previous limited approval history. However, on further consideration, the monograph has been amended to simply require "a suitable test and limit for dissolution that demonstrates the appropriate release of the active ingredient". This is considered appropriate and sufficient in this case.
One respondent provided comments in relation to the draft monograph for Dextromethorphan hydrobromide.
The respondent questioned why medicines containing dextromethorphan base (as opposed to hydrobromide) were not included in the monograph. While they accepted inclusion of "Helps soothe sore throats" as a label indication for lozenges, they suggested it not be included in the ARTG as a therapeutic indication. They suggested wording and formatting changes to the "Label indications" section, including allowance of a "fast" claim for liquid products. Finally, they questioned the proposed related substance limits and suggested ARGOM default limits be applied.
Dextromethorphan base was excluded from the monograph due to the TGA's very limited experience with this ingredient (only one medicine registered, several years ago).
Reference to 'helps soothe sore throats' was included in the accepted ARTG indications in accordance with previous approvals for lozenges, based on the accepted demulcent action of lozenges. The 'Label indications' section has been reworded to improve clarity and allowance of a "fast" claim for oral liquids has been included.
The test and limits for dextromethorphan related substances have been deleted from the monograph, taking into account the known stability of the active ingredient and noting that related substances would be adequately controlled through control of the starting material.
Laxatives – Docusate sodium and/or sennosides
One respondent provided comments in relation to the draft monograph for Laxatives – Docusate sodium and/or sennosides.
The respondent noted inconsistencies in the permitted patient population within the monograph and suggested that the advisory statement "Do not use in children under 12 years" be amended to "Not recommended for use…..", to be consistent with the required RASML statement.
The patient population has been amended to "Adults and children 12 years and over", consistent with recent correction to the RASML2 entry for hydroxyanthracene derivatives. The patient population is now consistent throughout the monograph.
The advisory statement in the monograph has been amended from "Do not use in children under 12 years" to "Not recommended for use in children under 12 years", consistent with the newly required RASML2 advisory statement for hydroxyanthracene derivatives (includes sennosides).
Each of the four respondents provided comments in relation to the draft monograph for Hand Sanitisers.
Two respondents questioned the omission of other active ingredients from the monograph (ie. triclosan, povidone iodine, benzalkonium chloride). One respondent requested inclusion of reference to active ingredient content by % w/w in addition to w/v.
One respondent raised concerns about the restrictiveness of allowable claims, including in comparison to those allowed for cosmetic products (eg. 'kills 99.99% of germs'). They considered that further clarification was required regarding permitted claims. Three respondents considered that claims for use in food preparation and handling should be permitted. Two respondents noted that food handling claims can be made for cosmetic products, one noting that such claims were not therapeutic claims and another noting that such claims have been approved in the past for registered hand sanitisers. One respondent suggested that use in food handling should be encouraged and suggested inclusion of reference to use prior to donning gloves for food handling.
One respondent considered that modification of specified test methods should be permitted if suitably justified by the applicant.
Directions for use and labelling
One respondent noted that requirements for specifying directions for use were more restrictive in the monograph than for cosmetic hand sanitisers and that allowance should be made for expressing directions in a more practical manner (eg. specifying "sufficient to wet the hands" instead of "5 ml"). They also questioned the need for the monograph to reproduce labelling requirements specified in the RASML and SUSMP.
One respondent considered that content limits for each of the active ingredients should be broadened to 90-110%) and that total impurity limits for chlorhexidine gluconate hand sanitisers should not be necessary. Another respondent suggested replacing reference to "tint" with "colouring" and requested clarification regarding when a test for pH was required.
One respondent suggested additional wording in the 'Introduction' of the monograph to clarify that the monograph does not cover Excluded Goods. Another respondent raised several broader issues regarding definitions, advertising, sale and overuse of hand sanitisers and suggested that further information regarding use of hand sanitisers be included in the monograph.
The active ingredients specified in the monograph were included on the basis of TGA experience with existing registered and recently evaluated products. Benzalkonium chloride has not been included in the monograph as the TGA has limited experience with this active ingredient in hand hygiene products. Products containing povidone-iodine have not been included as they are mostly indicated for use as surgical scrubs, which are not the subject of the proposed monograph. Triclosan has now been included in the monograph for use in hand-wash preparations only. TGA experience with use of triclosan-based hand rubs is presently limited.
Ethanol and isopropanol concentrations are expressed in %v/v, consistent with most literature references that refer to their antiseptic efficacy. Because the specific gravity of the formulated product varies significantly depending on the excipient composition, it is not possible to provide corresponding values for %w/v or %w/w in the monograph. However, provided the concentration of alcohol is within the range specified in the monograph, formulation details in the ARTG and on the label can be declared as %w/w.
The claims permitted in the monograph are consistent with those accepted for fully evaluated registered products. An important distinction between antibacterial hand hygiene products marketed as cosmetics and OTC registered antiseptic hand hygiene products is that cosmetics product are only intended to be used in domestic/commercial settings whereas OTC registered products are intended to be used in healthcare settings. A claim such as 'kills 99.99% of germs' is not appropriate for OTC antiseptics as it implies that the product is effective against 99.99% of the types of pathogens that are likely to be encountered in a healthcare setting.
Under Food Safety Standards 3.2.2, a food handler is expected to wash their hands whenever their hands are likely to contaminate food. Antibacterial/sanitiser hand gels are not an alternative to hand-washing in the food preparation area. If hand-rubs are used alone instead of hand-washing, there is the potential for contamination of food by chemical residues from hand-washing. In addition, the presence of fatty and proteinaceous materials on the hands can significantly reduce the antimicrobial efficacy of an alcoholic hand-rub. A claim such as "suitable for use by food handlers" may inappropriately encourage food handlers to use the hand-rub as an alternative to hand-washing. For this reason, the TGA considers that labels for antiseptic hand-rubs should not include a claim suggesting that the product is suitable for use by food handlers. Claims in relation to food-handling are acceptable for hand washes and this has been further clarified in the monograph.
In relation to the use of modified test methods in assessing the antiseptic efficacy of the product, it should be noted that this option is available for OTC products that are submitted via the N3 to N5 routes. The N2 route is only applicable when the medicine complies with N2 application requirements and there is no evaluable data required to be included in the application. Use of a modified method needs evaluation to determine whether the method is equivalent to the methods described in the N2 monograph.
Directions for use and labelling
In relation to the suggestion that the directions for use on the label need not reflect the way the product was used during antimicrobial efficacy testing, it should be noted that the amount of antiseptic applied to the hand and the length of time the antiseptic is in contact with the skin is critical to the antimicrobial effectiveness of the product. Since OTC antiseptics are to be used in healthcare settings, it is essential for the label directions to be consistent with those used in the antimicrobial efficacy testing of the products. When OTC antiseptics are evaluated, sponsors are required to provide data in relation to volume dispensed per pump and on this basis the labels are required to specify the number of pumps in the directions for use to ensure that they reflect the test conditions. Recognising that it is not always possible to measure the volume of the product applied to the hands, the 'Directions for use' section has been amended to allow reference to the number of pumps required or inclusion of directions such as 'deliver sufficient quantity of the liquid to wet the entire hand and to keep it wet for X seconds'.
In relation to the reproduction of labelling statements from RASML and SUSMP, the TGA consider that for this monograph it is preferable to reproduce the statements to further assist sponsors, noting in particular that for chlorhexidine gluconate, SUSMP requirements are more difficult to identify.
The TGA agrees to widen the expiry limits for the active ingredients to 90-110%, consistent with previous medicine approvals. Wording in the monograph specifying when a pH test is not required has been amended for clarity to refer to 'alcohol based hand-rub preparations that do not contain any excipients other than water', with reference to 'tints' now deleted. Test and limits for total impurity limits for chlorhexidine gluconate have been deleted, consistent with previous medicine approvals.
The TGA does not consider it necessary to specify that the monograph does not cover Excluded Goods. The purpose of the monograph is to set out criteria to be fulfilled when a sponsor wishes to register an antiseptic hand-hygiene product as an OTC medicine through the N2 application route. It is not a Standard for the purposes of the Therapeutic Goods Act and does not apply to any product that is not the subject of a registration application as an N2 medicine.
The TGA notes and appreciates the additional comments provided in relation to regulation, labelling and use of hand sanitisers. Development of the monograph has not involved significant review of existing registration requirements at this time. Rather, the intention has been primarily to capture existing registration requirements in a clear and consolidated manner so as to permit self-assessment and certification based on current requirements. Additional issues outside this scope would need to be considered separately. In this regard, further review of requirements for hand sanitisers and related medicines is anticipated in the future. Consequent changes to regulation as a result of further review would result in amendments to the monograph as necessary.
The revised monographs are now available on the OTC medicine monographs webpage for use in submitting N2 applications.