Regulatory impact statement (RIS) - update to the Required Advisory Statements for Medicine Labels (RASML)

May 2013

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The Regulatory Impact Statement (RIS) prepared by the TGA in May 2013 documents the proposal to update the Required Advisory Statements for Medicine Labels (the RASML) to:

  • Include new and amended mandatory advisory statements.
  • Implement the RASML document as a Legislative Instrument.

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1. Executive summary

May 2013

The labels of non-prescription medicines should provide self-medicating consumers with sufficient information to choose the medicines appropriately and to use the medicines safely and effectively.

In order to ensure that important safety information is included on non-prescription medicine labels, the Therapeutic Goods Act 1989 mandates the inclusion of advisory statements on some labels. These statements are currently compiled in the Required advisory statements for medicine labels ('the RASML'), which was published in September 2008.

From time to time it is necessary to review the mandatory advisory statements and to update the RASML to include new/revised statements where appropriate.

The need for new advisory statements can arise when new medicines are evaluated and approved by the TGA for supply to the Australian market. Some of these new medicines have risks that require new advisory statements. Additional risks may subsequently be identified via post-market pharmacovigilance and regulatory activities, or publication of new scientific or clinical information. New risks may also arise from a change to the level of scheduling of a medicine that results in greater consumer access.

The TGA proposes to update the current version of the RASML to incorporate a number of new advisory statements.

Stakeholders were consulted throughout the RASML update process over the past 3 years. Stakeholders generally supported adoption of the proposed updated RASML. Specific issues raised by stakeholders in relation to individual statements were considered by the TGA, and acted on where appropriate.

If the proposal to update the RASML is accepted, industry will be advised and the document will be finalised and published on the Federal Register of Legislative Instruments (FRLI). Supportive information and a link to the FRLI will be published by the TGA on its website to ensure that sponsors and manufacturers are fully informed of the new and amended requirements. The proposed date of commencement of the updated RASML will allow time for sponsors and manufacturers to comply with the new requirements.

The new (updated) RASML will result in one-off costs to industry associated with the amendment of labels that are impacted by the changes. However, these costs will be minimised by the proposed phase-in period allowed for implementation of the changes. Relevant stakeholders are already aware of the proposed changes and the possible costs as a result of the consultation process already undertaken with regard to the RASML update. In the long term there should be benefits to all stakeholders from the increased transparency of the TGA's requirements.

2. Introduction

May 2013

2.1 Background

Adverse events associated with medications are common, affecting a substantial number of people and placing a significant burden to health care costs. In Australia, approximately 2-3% (or 190,000) of annual Australian hospital admissions are medication related,i,ii with an estimated cost to the health care system of $380 million to $660 million. About half of these medication-related admissions are due to medication errors which are considered potentially preventable. Overseas studies report similar figures.iii,iv

All medicines have risks associated with their use. Some risks are general risks for all consumers, while other risks are specific to a set of consumers. For example, some medicines should not be taken by pregnant women, as there may be harmful effects on the foetus. Some medicines should not be taken by people with medical conditions such as heart disease, kidney disease or liver damage, or by people taking other medicines at the same time. There are also medicines that can cause side effects that all consumers should be aware of, such as drowsiness at normal doses, or serious side effects in overdose. The risks that a medicine may pose may be reduced by measures such as a smaller pack size and adequate directions on the label. Measures such as these can allow the medicine to be regulated under a lower regulatory framework (e.g. OTC rather than prescription) without compromising patient safety.

2.2 Current regulation of non-prescription medicines in Australia

As of 1 August 2012, there were 14,589 non-prescription medicines (sponsored by 992 companies) included on the Australian Register of Therapeutic Goods ('the ARTG'). Information published by the Australian Self Medication Industry Association (ASMI) indicates that the current value of the Australian non-prescription medicines market (grocery and pharmacy combined) is about $3 billion. Grocery stores (including supermarkets and healthfood stores) account for 26% of the market; pharmacies account for 74% of the market.

Non-prescription medicines supplied in Australia must be either listed or registered on the ARTG in accordance with the requirements of the Therapeutic Goods Act 1989 ('the Act') and the Therapeutic Goods Regulations 1990 ('the Regulations').

Under section 25 and section 26 of the Act, the TGA delegate of the Secretary must be satisfied that medicines that are proposed to be registered or listed on the ARTG satisfy a number of specific criteria, including:

  • acceptable quality and safety (and efficacy in the case of registered medicines)
  • presentation that is not unacceptable
  • compliance with applicable standards.

In addition to its own expert staff, the TGA currently has the following four statutory advisory committees from which it obtains independent expert advice on specific scientific and technical matters to aid the TGA's regulatory decision making.

  • The Advisory Committee on Complementary Medicines (ACCM) advises and makes recommendations to the TGA regarding the entry of complementary medicines on the Australian Register of Therapeutic Goods.
  • The Advisory Committee on Non-prescription Medicines (ACNM) advises and makes recommendations to the TGA regarding the entry of non-prescription medicines on the Australian Register of Therapeutic Goods.
  • The Advisory Committee on the Safety of Medicines (ACSOM) advises and makes recommendations to the TGA on the safety of medicines and risk assessment and risk management of medicines.
  • The Advisory Committee on medicines scheduling (ACMS) advises and makes recommendations regarding how medicines and chemicals will be made available to the public1.

Committee members are appointed by the Minister and must have expertise in relevant clinical or scientific fields or appropriate consumer issues. The advice provided by these committees is an important element in the undertaking by the TGA of its regulatory functions, and forms part of the information that is available to a TGA delegate making a regulatory decision under the Therapeutic Goods Act.

Once a medicine has been approved for supply in Australia, the TGA monitors its ongoing safety and quality by conducting a range of monitoring activities, such as audits of efficacy, manufacturing facilities, collection and assessment of adverse reaction reports and laboratory testing of product samples. The TGA also works with international medicines regulators to identify signals that may indicate a safety issue associated with a medicine.

Where such signals are detected, the TGA has the powers to take prompt and proportionate regulatory action to minimise risks. Such action could include requiring the addition of advisory statements to medicine labels, adding conditions to the continued supply of the medicine, or product recall, suspension or cancellation. The medicines industry is an active participant in this process (e.g. conduct their own monitoring of adverse events etc).

The regular review of medicine labels to reflect new or revised advisory statements is a long standing international industry practice that is conducted in cooperation with medicines regulators in Australia and overseas.

2.3 The importance of labels for non-prescription medicines

Non-prescription medicines can be purchased with minimal advice from health professionals. In particular, medicines available in grocery stores can be purchased with no advice. In the absence of professional health advice, consumers are vulnerable to any potential harm that could be caused by use of the medicines. For users of non-prescription medicines, the medicine label is therefore an important source of information about the medicine. In some cases, the label is the only source of information.

At the point of sale, the information provided on the label of non-prescription medicines must allow the consumer to quickly and easily make a choice about the suitability of the medicine (i.e. is it the right one for their needs). The label should also provide the consumer with information about important risks associated with use of the medicine. The risks may mean that some consumers should not use the medicine at all.

At the point of use, consumers should have access to instructions for using the medicine safely and effectively. This is particularly important for medicines that treat recurring minor ailments such as headaches, coughs and colds. Consumers may store such medicines at home to have available when and if needed, and any verbal advice that was provided when the medicine was purchased may well be forgotten when the medicine is used.

2.4 Current enforcement of mandatory advisory statements on medicine labels

Mandatory advisory statements for non-prescription medicines are currently compiled in the Required advisory statements for medicine labels ('the RASML'). The current RASML is published on the TGA website; and is not a legislative instrument.

The first version of the RASML (published on the TGA website on July 2004) was a compilation of the relevant requirements of the Regulations and the Schedule for the Uniform Scheduling of Drugs and Poisons (SUSDP)2. There have been three updates to the RASML since its initial publication. These updates incorporated the requirements of new 'Listing Notices'3, as well as recommendations of the National Drugs and Poisons Scheduling Committee (NDPSC) in regards to non-prescription analgesics ('pain-killers') and fluoride-containing medicines.

The current edition of the RASML (September 2008) is enforced under the Act through reference in the Therapeutic Goods Order No. 69C - Amendment to Therapeutic Goods Order No. 69 General requirements for labels for medicines ('the Labelling Order'), which is a standard under the Act.

Under the new sections 3(5)(ca) and 3(5A) of the Act, which came into force in 2009, the presentation of a medicine is unacceptable if the medicine's label does not contain advisory statements specified by the Minister by legislative instrument. In the Explanatory Memorandum to these new sections of the Act it was indicated that the RASML was intended to be the basis for this new instrument (the instrument does not yet exist).

However, even where an advisory statement is not included in the RASML, the TGA delegate of the Secretary can still take action under sections 25, 26 and/or 28 of the Act to enforce the advisory statement (or refuse to register or list the medicine), if the safety and/or presentation of the medicine are considered unacceptable without the statement.


Footnotes

  1. Medicines and chemicals are grouped into Schedules according to the appropriate level of regulatory control over their availability (e.g. Schedule 4 - medicines available only by prescription; Schedule 3 - medicines available only from a pharmacist; Schedule 2 - medicines available over the counter in pharmacies).
  2. The SUSDP has subsequently been renamed the Schedule for Uniform Scheduling of Medicines and Poisons, and enabled as the Poisons Standard.
  3. See explanation of Listing Notices in Appendix 1.

3. The problem

May 2013

3.1 The need for an updated RASML

Since publication of the current RASML in 2008, the TGA and its statutory advisory committees have recommended inclusion of a significant number of additional advisory statements in the RASML. The currently proposed update to the RASML includes over 50 new and/or changed requirements affecting 68 medicines; which will result in changes to the labels of over 500 individual products (and affecting over 70 sponsors).

Some of the new advisory statements have been recommended as part of decisions to approve new medicines. Others have been considered necessary to reduce new risks due to changes to the level of scheduling of medicines that have resulted in greater consumer access. In other cases, statements have been recommended to mitigate new risks that have been identified for existing medicines (i.e. medicines that are already on the ARTG), through post-market pharmacovigilance and regulatory activities in Australia or overseas, or from publication of new scientific or clinical information related to the medicine.

When warning statements are considered necessary for reasons of consumer safety, the TGA will require sponsors to include these statements on medicine labels regardless of whether or not the statements are included in the RASML.

For example, in 2012 the TGA published changes to cough and cold medicines for use in children arising from a review of the safety and efficacy of over-the counter medicines containing one or more of 22 medicine substances. The outcomes of the review included recommendations that over-the-counter cough and cold medicines should not be used by children under 6 years of age, and that there should be advisory statements on the labels of products that have doses for children aged 6 to 11 years, to the effect that the products should only be given to children in this age range on the advice of a doctor, pharmacist or nurse practitioner. The TGA sent Section 28 notices to sponsors who currently had products included on the ARTG to ensure that the labels were updated. To ensure that future products are also labelled correctly, the TGA also proposed that the advisory statements would be included in the next update of the RASML document.

The TGA also routinely incorporates other newly recommended advisory statements into guideline documents, such as the Australian regulatory guidelines for over-the-counter medicines ('the ARGOM')4, and negotiates with individual sponsors on a case-by-case basis as part of individual applications to approve new or varied medicine labels.

For example, a new advisory statement is proposed for anticholinergic medicines (including Atropa belladonna, Datura spp., Hyoscyamus niger, and compounds of atropine [excluding atropine methonitrate], hyoscine and hyoscyamine), which are used for conditions such as travel sickness, stomach aches and diarrhoea. The proposed new advisory statement was recommended for inclusion in the RASML by the National Drugs and Poisons Schedule Committee (NDPSC) in October 2007, but could not be included in the current RASML due to publication deadlines. The NDPSC was concerned about the potential for anticholinergic agents to mask serious conditions if used for an extended period of time. Therefore, the NDPSC made a recommendation that all anticholinergic products should include a warning statement not to use the medicine for more than 2-3 days without medical advice. Currently the TGA asks sponsors to include this statement on labels that are submitted for TGA review. Sponsors regularly comply with this request, for reasons of consumer safety.

However, the existence of multiple sources of recommendations and requirements for advisory statements is inconsistent with the intention of the RASML document, which is to be a complete and comprehensive source of the advisory statements that are required to be included on the labels of non-prescription medicines supplied in Australia.

The lack of transparency caused by the multiple sources of requirements and recommendations, together with the TGA's inability to enforce recommendations that are not in the RASML, has consequences for consumers, health professionals, industry and Government.

Where advisory statements are necessary for safe and effective use of a medicine, the absence of these statements could potentially result in harm to consumers and impact on public health. The size of the detriment that is currently occurring is unknown, although likely to be low. This will be discussed further under Impact Analysis, below.

The lack of transparency also leads to direct costs to sponsors resulting from delays to the processing of applications due to the need for label revisions. Any costs that are incurred by sponsors due to inconsistent and confusing application of requirements for advisory statements may also be transferred to consumers in the form of increased prices.


Footnotes

  1. The ARGOM describes the information to be supplied with applications to register OTC medicines in the ARTG. These medicines will be subject to evaluation by the TGA, in accordance with Section 25 of the Act, prior to inclusion in the ARTG.

4. Objectives

May 2013

The primary objective of government action in relation to mandatory advisory statements is to reduce the incidence of adverse events, and therefore reduce consequent consumer harm and public health costs, by ensuring that the non-prescription medicines supplied to the Australian community are labelled with information that will make the use of the medicines as safe and as effective as possible.

The secondary objective is to minimise administrative costs for industry thereby supporting the commercial viability of non-prescription medicines to Australian consumers.

5. Options

May 2013

There are three options: A - maintain the status quo, B - proceed with the proposed RASML update and update the Labelling Order to refer to the updated RASML document, or C - implement the proposed RASML update as a legislative instrument, and update the Labelling Order to refer to this instrument.

5.1 Option A - Maintain the status quo

If the status quo is maintained, then the Labelling Order will continue to refer to the current (September 2008) version of the RASML that is published on the TGA website.

5.2 Option B - Update the RASML document to include new labelling requirements

Under this option, the RASML document will be updated to include the additional labelling requirements that are recommended by the TGA, and the Labelling Order will be updated to refer to the new document.

5.3 Option C - Update the RASML document to include new labelling requirements and enable the updated RASML as a legislative instrument

Under this option, the RASML document will be updated to include the additional labelling requirements that are recommended by the TGA, and the updated RASML will be made a legislative instrument in its own right. The Labelling Order will then be amended to refer to the Legislative Instrument.

6. Impact analysis

May 2013

The options identified above will each have impacts on consumers, industry (Australian sponsors), government and the public health system.

6.1 Option A - Maintain status quo

In the short term, the absence of any immediate requirement to make changes to medicine labels will result in an absence of any immediate costs to industry.

In the long term, the existence of multiple sources of requirements and recommendations, together with the TGA's inability to enforce recommendations that are not in the RASML, could lead to a number of adverse consequences, as detailed below.

6.1.1 Impact of Option A for Australian consumers

If the status quo is maintained, the advisory statements that do not have a legislative basis (i.e. not mandatory) will continue to be inconsistently applied to the labels of OTC medicines.

Consumers may be denied contemporary information that they need to inform their use of medicines. If this leads to consumer harm, consumers and the public health system could face significant costs.

The case-by-case inclusion of advisory statements that are recommended by the TGA (but that are not directly enforceable) will also result in inconsistent labelling of similar medicines supplied by different sponsors. The case-by-case enforcement of TGA-recommended statements that have not been standardised and optimised by a process of public consultation may also lead to considerable variation of the wording on different products, which could cause consumer confusion. Confusion and misunderstanding could lead to decreased compliance with important safety advice, with the consequent potential for consumer harm.

For example, if a non-enforceable advisory statement related to the duration of use of a pain-killer medicine (e.g. 'only for short-term use') is included on the label of one brand, but not on the label of another brand, then a consumer might think that the brand without the statement can be taken for longer than the brands that do include the statement.

As stated previously in this document, adverse events associated with medications place a significant burden to health care costs. In Australia, approximately 2-3% (or 190,000) of annual Australian hospital admissions have been estimated to be medication related, with an estimated cost to the health care system of $380 million to $660 million. About half of these medication-related admissions are due to medication errors which are potentially preventable.

6.1.2 Impact of Option A for industry / Australian sponsors and the Australian Government

The absence of any requirement to make immediate/phased-in changes to medicine labels can be viewed as a short-term cost-saving benefit to the industry. However, Option A will have ongoing costs for all stakeholders.

The RASML does not currently fulfil its intended role as a single reliable source of advisory statements that are required by the TGA. Maintaining the status quo by failing to update the RASML will lead to ongoing compliance costs for industry. In order to ensure that proposed medicine labels include all of the appropriate requirements, sponsors must currently consult multiple sources, including the published RASML consultation document, the ARGOM, the Electronic Listing Facility5 and new Listing Notices.

Apart from the statements that result from Listing Notices, the new and amended advisory statements in the draft RASML update are not currently enforceable through legislation; however, the TGA does attempt to enforce inclusion of safety-related statements on labels as a condition of registration of individual medicines. When a sponsor applies to register or list a medicine on the ARTG, or to vary the labels of a medicine, the Act requires the TGA to determine whether the safety and efficacy of medicines has been satisfactorily established, for the purposes for which they are to be used. As part of such an application, the TGA may request that the sponsor include a new advisory statement on the labels, for reasons of safety under the Act. Under the 'status quo' option, this case-by-case practice of requesting non-enforceable inclusion of statements on labels would continue.

If the status quo is maintained, there could be extra costs to industry associated with the redrafting of medicine labels that are submitted to the TGA without all of the necessary requirements, and with the consequent delay in approval of the new labels.

Inconsistent inclusion of advisory statements on different brands of the same medicine could also lead to an unfair marketing advantage to sponsors whose products appear to be safer or appear to be suitable for broader use (e.g. for more long term use or for a wider patient population) than other similar products that have warnings and restrictions on their labels.

There may also be disadvantage to industry when the inclusion of a statement on one sponsor's product sets a precedent for all other similar products without any public consultation having taken place.

Any costs that are incurred by sponsors due to inconsistent and confusing application of requirements for advisory statements may be transferred to consumers in the form of increased prices.

It is also possible that there could also be very extensive financial costs to industry and public health from later regulatory action such as medicine recalls or more restrictive scheduling of medicines that result from incidents of consumer harm.

6.2 Option B - Update the RASML document to include new labelling requirements

In the short term, industry will incur extra costs due to implementation of new labelling requirements. These costs might be transferred to consumers. However, once all of the existing products are compliant with the new requirements there will be no additional ongoing costs. In fact, the ongoing costs in relation to labelling compliance are expected to be reduced compared to Option A due to the advantages of having all of the requirements published in one place. Under Option B, all of the ongoing costs associated with Option A will be minimised or avoided.

As discussed below, the RASML update provides transparency and enforceability of advisory statements. Enforceability will ensure that the new advisory statements are consistently present on medicine labels. This should result in a 'level playing field' for industry, and should also assist consumers in avoiding potential harm from use of the medicines. It is expected that there will be reduced administrative costs to industry and the TGA from introduction of the updated RASML as a single authoritative source of required advisory statements.

6.2.1 Impact of Option B for Australian consumers

Benefits for public health

Under this option it is expected that advisory statements that are considered necessary for public safety reasons will be consistently applied, as the requirements will be in a single source document and be able to be legally enforced.

New safety information continues to emerge due to monitoring of adverse events internationally and in Australia. Provision of this information to consumers via advisory statements can reduce patient harm by informing consumers of the way medicines should be used, and when they should seek advice.

For example, there have been several recent international reports of renal toxicity occurring in dehydrated but otherwise healthy children who were given commonly available NSAIDs such as ibuprofen and naproxen. In Australia, in children and adolescents aged under 18 years, eight renal adverse reactions involving ibuprofen and seven involving naproxen have been reported to the TGA, including six reports of renal failure (three reports for ibuprofen, and three for naproxen). The current RASML update proposes mandatory statements for the labels of NSAIDs products advising care givers to ask a doctor or pharmacist for advice before using the medicines in children who may be dehydrated through diarrhoea or vomiting.vii

Another example of new information on adverse events for existing products relates to international concerns about adverse effects from overuse of choline salicylate teething gels in infants. In other countries, these concerns have resulted in products containing choline salicylate being either withdrawn from the market (e.g. in the United Kingdom) or subject to labelling changes (e.g. in New Zealand). In Australia, the relevant expert committees have advised that the products should remain available, but that labelling requirements should be introduced to improve the dosage instructions and to advise parents and carers not to exceed the recommended dose.

While label warnings may not always be effective, the study by Ley described above indicated that the effectiveness of warnings can be improved by optimising the wording. In this context it should be noted review of the proposed statements by stakeholders was part of the consultation process for the RASML update.

The ongoing management of newly identified medicine risks via application of advisory statements rather than other regulatory approaches (such as withdrawing the products from the market, restricting the indications, restricting the patient groups, or restricting the medicine scheduling as prescription only) allows consumers to have best possible access to medicines while also being adequately informed of how best to use medicines safely and effectively.

6.2.2 Impact of Option B for industry / Australian sponsors and the Australian Government

One-off costs

The proposed update to the RASML includes over 50 new and/or changed requirements.

The majority of the proposed new advisory statements have been available to sponsors for 1-3 years, having been published on the TGA website, most recently as the 'RASML 6' consultation document (published February 2011) and the TGA response to submissions (March 2012). However, until the new advisory statements are finalised and incorporated in the legislation, sponsors cannot be certain of the requirements that will apply. In view of the costs involved in updating medicine labels, some sponsors may have chosen not to include the proposed statements on their labels until they are certain of the requirements.

Some of the proposed changes will not involve any cost to industry, as the affected medicines are already compliant with the proposed update. These include proposed new advisory statements that originate from long-standing specifications of the ARGOM and the Electronic Listing Facility, as well as new Listing Notices.

Other situations where medicines may already be compliant with the proposed updated RASML include the following:

Changes that have limited or no adverse impact on sponsors or manufacturers of current products are detailed in Appendix 1.

However, for some of the new statements, there are situations where currently supplied medicines will not yet be compliant. In these situations, the statements are likely to have some impact on stakeholders.

The statements that are likely to have an impact on stakeholders include those proposed for currently registered or listed non-prescription medicines as a result of TGA Expert Committee recommendations made after the publication deadline for the current RASML in 2008. These include the new and updated RASML for the medicines listed below:

  • Anticholinergic medicines used for conditions such as travel sickness, stomach aches and diarrhoea
  • benzydamine, which is used for sore throat
  • chlorhexidine in topical antiseptics
  • choline salicylate, which is used in products such as teething gels
  • coal tar in topical products for relief of itchy skin and scalp conditions
  • non-steroidal anti-inflammatory drugs (NSAIDs) (including diclofenac, ibuprofen, indomethacin, ketoprofen and naproxen) that are used for pain relief
  • fluconazole, an antibiotic
  • fluorides, when in medicines such as oral fluoride supplements that are scheduled S2 (Pharmacy Medicine) or S3 (Pharmacist Only Medicine)
  • proton pump inhibitors (lansoprazole, pantoprazole, omeprazole) used for gastric reflux and stomach ulcers
  • vitamin B6 supplements (pyridoxal, pyridoxine and pyridoxamine).

In some cases (e.g. benzydamine) only a small number of products will be affected by the new or amended statements, whereas the requirements for some other substances will affect multiple products and sponsors. For example, in the case of anticholinergics, there are at least 16 affected products registered on the ARTG, corresponding to at least 7 sponsors. The wording of the proposed statement that is recommended by the TGA was published in the RASML 6 consultation document in 2011, but some sponsors will be waiting to amend their labels until they are sure of the requirements.

Medicines that are impacted by the new or amended advisory statements are also detailed further in Appendix 3.

Cost estimates

Overall, the changes are expected to result in amendments to the labels of over 500 individual products (and affecting about 70 sponsors).

The actual number of impacted businesses, and total cost is not known precisely.

Costs to business include both the direct expense of designing and printing new labels that comply with the updated RASML, as well as costs incurred by the fees applied by the TGA for approval of the new labels.

  • The typical design and printing cost of a simple change involving only one printing plate has been estimated to be about $1500 to $2000. More complicated changes could cost $6,000 or more6,
  • The current TGA application and evaluation fees are given in the table below.
TGA regulatory fees for changes to OTC medicines Cost (including GST)
Application fee $1,370
Evaluation fee $3,310
  • However, it should be noted that the TGA evaluation fee is not applicable if the label is amended solely by addition of a new advisory statement required by legislation. In this case the TGA only charges the application fee.

The actual costs will depend on many factors. For example, design and printing costs will be increased where there are several marketed pack sizes, and/or both primary pack and container labels for each product registration. Typically blister in carton packs will have one artwork impacted (ie carton), while bottle in carton, tube in carton or sachet in carton have two artworks impacted. The costs per product due to TGA fees will depend on how many labels can be included in a single application.

The actual total costs will also depend on the number of products that are already compliant (as discussed above), and the number of registered products that are not actually marketed, as well as the time period allowed for phase-in of the changes. Unforeseen labelling changes that require immediate implementation can lead to substantial direct costs due to wastage of stocks of already-printed labels together with the cost of a new unscheduled print run, or overstickering of existing stock. However, if adequate time is allowed for sponsors and manufacturers to incorporate the change into the next scheduled print run, any extra design and printing cost due to the new statement should be negligible.

Using 'worst-case' figures above, the total cost for 500 products could be over $5,000,000. However, in a hypothetical scenario where the printing and design costs average at $2000 per product, and the TGA fees average at $1370, a total hypothetical cost for 500 products can be calculated to be less than $2,000,000.

Ongoing benefits

Once all existing products are compliant with the new requirements, there will be no ongoing costs arising from the introduction of the updated RASML. Indeed, the ongoing costs in relation to labelling compliance are expected to be reduced compared to maintaining the status quo due to the advantages of having all of the requirements published in one source document.

The regular public consultations that are part of the RASML update process will lead to reduced costs to industry resulting from the opportunity to have input into proposed and existing requirements. The usefulness of this input is evident from the results of the public consultation held in the context of the draft 'RASML 5' and 'RASML 6'. The TGA took stakeholder suggestions for amendments to the proposed requirements into account for 38 out of the 46 cases where stakeholder input was provided.

An up-to-date and complete RASML will be of benefit to both industry and the TGA as the updated RASML will identify the advisory statements that are required for particular products.

Certainty in regards to labelling requirements for medicines should result in reduction in compliance costs associated with medicine applications. There should be fewer time delays and inconvenience in relation to the processing of applications for new registrations and variations to labels if sponsors are aware of the particular requirements.

As a result of the consultation process that has been undertaken, the statements that are proposed for inclusion in the updated RASML have already been agreed to in principle by all relevant stakeholders in the interests of safe and effective medication management. Sponsors have indicated that updating of the RASML would be generally welcomed.

6.2.3 Overall impact of Option B

Updating the RASML will result in some immediate costs to sponsors and manufacturers for updating the labelling for currently marketed products affected by new requirements. However, these short-term costs are likely to below.

As a result of the consultation process that has been undertaken over a period of several years, industry has had advance warning of the changes, and has had the opportunity to voluntarily incorporate the changes as part of label updates undertaken for other reasons. The TGA published the proposed 'RASML 6' document on the TGA website in February 2011 as part of the consultation process. The TGA response to stakeholder submissions to the consultation was published on the TGA website in March 2012. Where proposed statements were amended as a result of the consultation, the TGA response clearly stated the amendments.

The Australian Self Medication Industry Association (ASMI) stated in its published submission to the recent 'RASML 6' consultation that its "...members affected by the changes have, in general, commented that several of these proposed statements or similar are already on labels, having been required by the TGA as part of the registration/listing process", and that "...at least half of the proposed additions to this update arise from recommendations pre-2008, and one from 1998".

Industry has requested that the implementation time for introduction of the statements for existing products where there are no immediate safety concerns be increased from 12 months (as originally proposed by TGA) to 18 or 24 months, to allow the changes to be introduced as part of the sponsors' next scheduled label print run. The TGA is agreeable to an extended time of 18 months. This extended implementation time should provide opportunity to address the concerns that were raised by industry groups during the consultation (see under Communication and consultation, below).

Updating the RASML will result in ongoing benefits to all stakeholders due to the increased transparency and predictability of TGA requirements; with resultant ongoing reduction in compliance costs, together with a more 'level playing field' for different brands of similar medicines.

There should be ongoing benefits to the public as the presence of advisory statements can enable consumers to choose the right medicines for their needs, and to use the medicines more safely and effectively.

The amount of consumer harm that can be avoided by the proposed statements is likely to be low, and cannot be quantified precisely; however, any readily avoidable harm to otherwise healthy people taking non-prescription medicines is unacceptable.

6.3 Option C - Update the RASML document to include new labelling requirements and implement the updated RASML as a Legislative Instrument

The costs and benefits of this option will be identical to those for Option B, except that this option will have the additional benefit that it will avoid the need to update the definition of the RASML in the Labelling Order each time the RASML document is updated in the future.

The adoption of the RASML as a Legislative Instrument is in line with the intent of the Therapeutic Goods Amendment (2009 Measures No 2) Act 2009, which required that, from a date to be proclaimed, the Minister will be able to specify, by legislative instrument, advisory statements required to be included on the labels of specified medicines (see Explanatory Memorandum to the Therapeutic Goods Amendment (2009 Measures No. 2) Bill 2009).


Footnotes

  1. The Electronic Listing Facility (ELF) provides a web-based electronic lodgement facility for applications to list medicines on the ARTG.
  2. Figures are based on information provided from the ASMI, as well as information provided in the context of the recent consultation on adoption of the new sunscreen standard.

7. Communication and consultation

May 2013

'RASML 5' and 'RASML 6' consultations

Extensive consultation has been conducted for the currently proposed RASML update. The objective of the consultation was to obtain feedback on the level of support for the proposed changes, as well as any suggested improvements, and the likely benefits and costs of the revisions to stakeholders.

The consultation was conducted by publication of the proposed document together with explanatory information and request for public submissions. The most recent consultation period, in 2011, was three months.

In response to the consultation documents for the 'RASML 6' update, a total of 22 submissions were received, originating from peak industry group representatives (including the ASMI and the Complementary Healthcare Council (CHC)), individual pharmaceutical companies, pharmacy profession representative groups (Pharmacy Guild of Australia, Pharmaceutical Society of Australia, Pharmaceutical Council of Western Australia) and the consumer advocate group the Consumer Health Forum. Two individual stakeholders also provided comments.

None of the submissions included any general objections to updating the RASML document to reflect current requirements of the SUSMP, ARGOM, ELF and current standards and regulatory requirements for medicine labels.

There were a number of concerns about some individual statements, all of which were given thorough consideration by the TGA. The outcomes (including agreement to suggested changes where appropriate) were published on the TGA website.

Overall, the updating of the RASML was welcomed and considered long overdue.

The CHC stated that it "... strongly supports that the community be provided with appropriate information regarding medicines to enable them to make informed choices regarding their use, particularly medicines selected at retail". The CHC was concerned that Update 5 was never finalised, stating that this "...created uncertainty in relation to required statements".

The ASMI stated that "ASMI members affected by these changes have, in general, commented that several of these proposed statements or similar are already on labels, having been required by the TGA as part of the registration/listing process. For these statements therefore, this consultation is merely formalising the requirement for all products by inclusion in RASML". ASMI also stated that it was hopeful that the new legislative instrument status of RASML "...will indeed allow for this document to be updated more easily and more frequently. From both a safety perspective and that of practicality for implementation we suggest that the frequency of the update should be on a regular (e.g. annual) basis, rather than by whether there are sufficient statements to make consultation worthwhile".

The TGA acknowledged the stakeholder suggestions that there would be a benefit in a formalised process of informing stakeholders of the introduction of new advisory statements when the need arises, prior to the update of the RASML. Therefore in response to the stakeholder feedback, the TGA has implemented a change from the practice of accumulating the advisory statements which have arisen for one major consultation at the end of the year, to conducting individual "minor" consultations on new advisory statements for specific products as the need is first perceived. It is also hoped that this will assist in the provision of lead-in times for transition to new arrangements.

The submissions also raised concerns that a number of the advisory statements, both current and proposed, appeared to have a duplication of intent. It was suggested that current advisory statements be reviewed, with a view to consolidating, revising or archiving statements as appropriate. The TGA noted the merits of these comments and will consider the recommendations for inclusion in future consultations.

There was some concern from industry that the time period allocated for the implementation of the changes was not sufficient. It was suggested that for those products which do not have immediate safety concerns, the implementation period for existing periods be changed from a 12-month period to 18-24 months. The TGA proposes to increase the transition period to 18 months, to assist in minimising the impact of the changes to industry.

Cough and cold medicines for use in children- consultation on proposed advisory statements

In February 2012, the TGA sought comments from interested parties on proposed advisory statements for cough and cold medicines for use in children (for inclusion in the RASML document when it is next updated).

The TGA response to submissions included clarification of a number of issues, including the need to specify very clearly which professions are considered qualified to give advice on the use of medicines in children. The TGA also confirmed that it was the explicit conclusion of the safety review that no exceptions should be made for any of the 22 drugs reviewed.

Consultations for loperamide, fexofenadine, famciclovir, loratadine, desloratadine, azelastine, kunzea ambigua

In 2012 and 2013 the TGA has published requests for submissions in relation to proposed advisory statements for loperamide, fexofenadine, famciclovir, loratadine, desloratadine, azelastine and kunzea ambigua. Only two objections were raised, both in relation to proposed statements for famciclovir. The respondent was concerned about the potential for ‘information overload’ in relation to the proposed advisory statements 'If you have high blood pressure, heart problems, liver problems, diabetes or other medical conditions, consult your pharmacist or doctor before use' and 'If you have symptoms and signs of an infection other than your cold sore, consult your pharmacist or doctor before use'. However, the TGA responded that the proposed advisory statements would be retained in order to clearly identify patients in 'at risk' groups (who may have kidney problems or suppressed immune function).

8. Conclusion and preferred option

May 2013

Option C (update the RASML to include new labelling requirements and adopt the updated RASML as a Legislative Instrument) is the preferred option, as it best meets the safety and public health objectives of the TGA, as well as providing certainty and clarity for the pharmaceutical industry.

The initial compliance cost benefit for industry from maintaining the status quo (Option A) does not outweigh the long-term benefits to all stakeholders (including public health benefits) that will result from the update (Options B and C).

The adoption of the RASML as a legislative instrument should ensure a further reduced regulatory burden for those affected by required advisory statements in the future, as future updates will be incorporated and published promptly, rather than being delayed by the process of recognition of the updated RASML in the Labelling Order.

The proposal to update the RASML to include the labelling requirements that are recommended by the TGA will assist consumers in using medicines more safely and effectively, and will provide up-to-date, concise and transparent regulatory requirements for medicines labelling, which should lead to a long-term reduction in compliance costs for industry.

9. Implementation and review

May 2013

If the proposal to update the RASML is accepted, the RASML document will be finalised and industry will be advised (including through the TGA website and letters to industry associations).

The finalised RASML will be published on the Federal Register of Legislative Instruments (FRLI).

The date of commencement of the new Legislative Instrument will allow 18 months for sponsors and manufacturers to bring their products into line with the updated RASML.

The TGA website will include a link to the RASML on the FRLI, as well as extensive advice and information for stakeholders. In line with the current situation, the TGA website will also include an application form that any interested party can use to propose amendments to the RASML.

It is intended that the Legislative Instrument will be reviewed on a regular (preferably annual) basis after it is adopted. Each review will involve public consultation. The ongoing process of review of advisory statements that would be a part of this ongoing update process should lead to regular improvement in the content of the document.

Appendix 1

May 2013

Changes having negligible or no impact

The following types of changes are expected to have negligible or no impact on stakeholders.

Advisory statements from the Australian regulatory guidelines for over-the-counter medicines, 1 July 2003 ('ARGOM 2003')

There were 39 substances in the ARGOM 2003 for which TGA guidelines required advisory statements. Only some of these requirements were included in the RASML document at the time of its commencement in 2004. However, it was envisaged that these statements would be incorporated in the RASML at an appropriate later date.

Eleven ARGOM 2003 requirements are being introduced as part of the current RASML update.

The ARGOM has been adopted and used by the TGA and industry for over nine years. Many of the statements in the ARGOM have been required by the TGA for entry of medicines on the ARTG, and consequently the affected products currently on the market already satisfy the labelling requirements as set out in the ARGOM.

Advisory/warning statements required by the ELF

There are currently eight substances for which the ELF has required advisory statements since 2004:

  • aspartame
  • chitosan
  • folic acid
  • hydroxyanthrocene derivatives
  • iron compounds
  • psyllium
  • pyrethrins
  • royal jelly.

Although the advisory statements which apply to these substances were not included in the RASML document at the time of its commencement in 2004, marketed products have already been required to satisfy the labelling requirements as set out in the ELF as a condition of entry on the ARTG.

Advisory statements mandated by new Listing Notices

The Office of Complementary Medicines (OCM), within the TGA, regulates listed medicines containing low risk ingredients. Such medicines may only make low level health claims and must only include ingredients pre-approved by the TGA. The legislative basis for these ingredients falls under Part 1 of Schedule 4 to the Regulations, which identifies all the therapeutically active ingredients intended for use in listed medicines.

There is a mechanism for adding new ingredients to the list of goods or ingredients in Schedule 4 to the Regulations that qualify as 'listable'. Firstly, data submitted by an applicant is evaluated by the OCM. The OCM evaluation of these data focuses on determining whether the substance is of acceptable quality and is safe for use as a new ingredient. Following this, Subsection 9A(5) of the Act authorises the Minister for Health and Ageing to publish a 'listing notice' in the Commonwealth of Australia Gazette. The listing notice is used to notify stakeholders of the approval of a new ingredient eligible for use in listed complementary medicines. Once the listing notice is published, sponsors can include the ingredient in medicines that are eligible for listing.

The Listing Notice may sometimes require the labels of medicines containing the ingredient to include specific advisory statements. Seven of the listing notices published since 2008 include mandatory advisory statements. These listing notices apply to the following substances:

  • bovine whey IG-rich fraction
  • hydrolysed milk protein - alpha casozepine enriched
  • omega-3 fish oil phytosterol esters
  • potassium chloride
  • sodium bicarbonate
  • vegetable oil phytosterol esters
  • wheat dextrin
  • kunzea ambigua (OBPR has confirmed that no RIS is required - OBPR ID: 14808).

As these requirements are already mandatory under the Act, their inclusion in the RASML will not lead to any change that will have a regulatory impact on manufacturers and sponsors of therapeutic goods, or on the public.

Proposal to remove warning statements that are only applicable to S4 medicines from the main body of the document to the archival section

There are a number of existing advisory statements that were included in the original version of the RASML, but which only apply to Schedule 4 ('S4') medicines. These statements will be removed from the main body of the document to the archival section. RASML has no legislative application to S4 medicines.

New advisory statements as a result of recent down-scheduling decisions

In 2012 and 2013 the TGA new requirements have been proposed for famciclovir (as a result of down-scheduling from S4 to S3), azelastine (down-scheduled from S3 to S2), and for particular presentations of loperamide, fexofenadine, loratadine and desloratadine (down-scheduled from S2 to unscheduled). The new requirements for famciclovir are already being enforced as part of the applications to register the new OTC products. In regards to azelastine, there is currently only one sponsor of azelastine products (who is already compliant). In regards to the other products, the proposed advisory statements were published on the TGA website (as consultation documents) shortly after the down-scheduling decision was made in each case. The labels of the affected products would have been approved subsequent to this publication in almost all cases (albeit via 'self-assessable' applications). It is unlikely that there are many non-compliant products on the market.

Appendix 2

May 2013

Likely impact upon the industry group of each proposed types of changes
Propose changes Likely impact Comments
Inclusion of new advisory/warning statements which are mandated by Listing Notices (in relation to substances that are usually active ingredients in complementary medicines) introduced since 2009 No impact - Unlikely that sponsors will need to change the labelling of their current marketed products The condition for listing of the particular medicine on the ARTG would already require the warning statement to be included on the label.
Inclusion of advisory/warning statements as required by the Australian Regulatory Guideline on Over the Counter Medicines (ARGOM 2003) not previously included in current version of RASML No impact - Unlikely that sponsors will need to change the labelling of their current marketed products The sponsor would already have been required to include the warning statement on the label as part of evaluation of the application for registration of the particular medicine on the ARTG.
Inclusion of new advisory/warning statements required by the Electronic Lodgement Facility (ELF) not previously included in current version of RASML No impact - Unlikely that sponsors will need to change the labelling of their current marketed products The condition for listing of the particular medicine on the ARTG would already require the warning statement to be included on the label.
Inclusion of new or amended advisory statements as recommended by the Advisory Committee of Non prescription medicines (ACNM), Advisory Committee on Complementary Medicines (ACCM) and/or Advisory Committee on Safety of Medicines (ACSOM) as a consequence of medicine safety reviews (e.g. TGA review of cough and cold medicines for use in children) There could be impact on sponsors as there would be a need to change the labelling of current marketed products

Some warning statements introduced to ensure public health safety as a consequence of safety reviews of the medicines would be immediately communicated to the sponsors as a condition of registration under section 28 of the Act. In this case, the subsequent inclusion of the statements in the RASML would only impact new sponsors.

In other cases, there would be a need to amend the existing medicine labels as a consequence of its inclusion in RASML document, with the possibility of significant impact.

New or amended requirements as a consequence of changes to scheduling of the medicines in the Standard Uniform Scheduling of Medicines and Poisons (SUSMP) e.g. butoconazole, pantoprazole, omeprazole, fexofenadine No impact or minimal impact - Sponsors will not need to change the labelling of their current marketed products

Before a medicine can be marketed under the new schedule, new labels must be approved by the TGA.

In some cases, where the product was already in an OTC schedule, the labels are approved via 'self-assessable' applications and there is a possibility that they could be non-compliant. But the number of products affected in this way would be expected to be minimal.

Proposal to remove existing superseded warning statements from the main body of the document to the archival section No impact to the whole industry group Warning statements do not apply to any medicines, hence proposal to remove the warning statements from the main body of the document.

Appendix 3

May 2013

New or amended advisory statements that may have significant impact on many sponsors
Substance Change type Source Likely impact

Anticholinergics, including:

  • Atropa belladonna;
  • Atropine compounds (excluding atropine methonitrate)
  • Datura spp.;
  • Hyoscine compounds;
  • Hyoscyamine compounds;
  • Hyoscyamus niger.
New entries NDPSC recommendation Sponsors will need to change labelling of their current marketed products

Antihistamines including:

  • Brompheniramine
  • Chlorpheniramine
  • Dexchlorpheniramine
  • Diphenhydramine
  • Doxylamine
  • Pheniramine
  • Promethazine
  • Triprolidine
New entries Recommended as consequence of TGA review of cough and cold medicine for use in children Sponsors have already been required to change labelling of their current marketed products via individual section 28 Notices

Antitussives including:

  • Codeine
  • Dextromethorphan
  • Dihydrocodeine
  • Pentoxyverine
  • Pholcodeine
New entries Recommended as consequence of TGA review of cough and cold medicine for use in children Sponsors have already been required to change labelling of their current marketed products via individual section 28 Notices
Benzydamine New entry ARGOM 2003, OTC evaluation Sponsors may need to change labelling of their current marketed products
Carthamus tinctorius flower New entry Recommendation from Advisory Committee on Complementary Medicines (ACCM) to include warning statement Sponsors should not need to change the labelling of their products as the sponsors have been advised that the required warning statement is to commence from 1 July 2011.
Chlorhexidine New entry Amendment Recommended by the Medicines Evaluation Committee (now ACNM) and the Adverse Drug Reaction Advisory Committee (now ACSOM) Sponsors will need to change labelling of their products
Choline salicylate New entry Recommended by ACNM as a consequence of safety review Sponsors will need to change labelling of their products
Coal tar New entry OTC evaluations Sponsors will need to change labelling of their current marketed products
Diclofenac New entry Recommended by ACNM as a consequence of safety review Sponsors will need to change labelling of their current marketed products

Decongestants including:

  • Oxymetazoline
  • Phenylephrine
  • Pseudoephedrine
  • Xylometazoline
New entries Recommended as consequence of TGA review of cough and cold medicine for use in children Sponsors have already been required to change labelling of their current marketed products via individual section 28 Notices

Expectorants/mucolytics

  • ammonium chloride
  • bromhexine
  • Guaifenesin
  • Ipecacuanha
  • Senega and ammonia
New entries Recommended as consequence of TGA review of cough and cold medicine for use in children Sponsors have already been required to change labelling of their current marketed products via individual section 28 Notices
Fexofenadine New entry Recommended as consequence of down-scheduling decision, but also applied to current schedule 2 medicines Sponsors will need to change labelling of their current marketed products
Fluorides Amendment to include new warning statement Update of ARGOM Sponsors will need to change labelling of their current marketed products
Flurbiprofen Amendment to include new warning stateme ARGOM 2003 Sponsors will need to change labelling of their current marketed products
Ibuprofen New entry Recommended by ACNM as a consequence of safety review Sponsors will need to change labelling of their current marketed products
Indomethacin New entry Recommended by ACNM in reviewing a dermal preparation of NSAID Sponsors will need to change labelling of their current marketed products
Ketoprofen Amendment to include new warning statement Recommended by ACNM as a consequence of safety review Sponsors will need to change labelling of their current marketed products
Lansoprazole New entry Newly scheduled substance in Schedule 3 of SUSMP Some sponsors may need to change labelling of their current marketed products impact if the current label does not already have the advisory statement.
Loratadine and desloratadine New entries Recommended as consequence of down-scheduling decision for loratadine, but also applied to current schedule 2 medicines Sponsors will need to change labelling of their current marketed products
Naproxen Amendment to include new warning statement ARGOM 2003 Sponsors will need to change labelling of their current marketed products
Naproxen New entry Recommended by ACNM as a consequence of safety review Sponsors will need to change labelling of their current marketed products
Pantoprazole New entry, Amendment to include new warning statement Newly scheduled substance in Schedule 3 of SUSMP Some sponsors may need to change labelling of their current marketed products impact if the current label does not already have the advisory statement.
Pyridoxal Amendment to replace existing statement with new statement Existing warning statements deemed ambiguous, propose new statements as replacement by ACCM Some sponsors will need to change labelling of their current marketed products impact if the current label does not already have the advisory statement.
Pyridoxine Amendment to replace existing statement with new statement Existing warning statements deemed ambiguous, propose new statements as replacement by ACCM Some sponsors will need to change labelling of their current marketed products impact if the current label does not already have the advisory statement.
Pyridoxamine Amendment to replace existing statement with new statement Existing warning statements deemed ambiguous, propose new statements as replacement by ACCM Some sponsors will need to change labelling of their current marketed products impact if the current label does not already have the advisory statement.
Rabeprazole New entry Newly scheduled substance in Schedule 3 of SUSMP Some sponsors may need to change labelling of their current marketed products impact if the current label does not already have the advisory statement.

References

May 2013

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  2. Australian Council for Safety and Quality in Health Care. Second national report on patient safety: improving medication safety, 2002.
  3. National Prescribing Service Limited Medication Safety in the Community: A review of the Literature June 2009
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  7. Batagol R. Renal effects of NSAIDs, AJP 90 (October 2009): 24