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Regulation impact statement: Codeine re-scheduling
Version 1.1, December 2016
Overview of consultation activities
Consultation activities included receiving expert advice and recommendations from members of the Advisory Committee on Medicines Scheduling (ACMS), three formal invited public consultations following announcements of scheduling proposals on the TGA website and meetings with other internal stakeholders at the Department of Health.
In addition to formal public submissions made to the TGA regarding the re-scheduling of codeine, targeted formal consultation activities were held with stakeholders including five pharmaceutical companies, four peak bodies, and GPs.
Expert advice from Advisory Committee on Medicines Scheduling
The ACMS comprises independent experts as well as state and territory representatives who provide advice to the medicines scheduling delegate. The ACMS considered codeine re-scheduling at the July 2015 and March 2016 meetings.
At the meeting of the ACMS on 15 March 2016, the interim decision from 1 October 2015 to up-schedule codeine was reconsidered, including all of the public submissions and the external reports and evaluations. The committee also considered the alternative options including the reduction of pack sizes and label advisory statements, which were provided for public comment on 10 December 2015. The ACMS advice in March 2016 was consistent with the advice in August 2015.
The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 that can be considered by the committee included: (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity of a substance; (e) the potential for abuse of a substance; and (f) any other matters that the Secretary considers necessary to protect public health.
The ACMS recommended deletion of the current Schedule 2 and Schedule 3 entries for codeine, and that all codeine-containing products should be in Schedule 4 (prescription-only medications). Their reasons included:
- A greater risk of medication misadventure, dependence and deliberate misuse/abuse while also having a relative lack of efficacy compared to safer products. Changing the labelling and decreasing the pack size was considered to not adequately address these concerns
- OTC products are intended for the management of acute self-limiting pain, however, there is evidence of inappropriate use of OTC codeine for chronic pain
- Codeine shares the properties of other opioid analgesics and is potentially capable of producing dependence and, in overdose, respiratory depression and reduced level of consciousness
- Increasing amount of evidence of harm from abuse
- Misuse of OTC codeine products including deaths resulting from hepatic injury, gastrointestinal perforations, hypokalaemia and respiratory depression
- Minimal benefit of OTC products containing codeine compared to the risk profile, which raised broader questions regarding the role of codeine in clinical practice, and
- To adequately determine the clinical needs of the patient suffering chronic or severe pain, an appropriately qualified medical practitioner should assess risk.
Formal consultation periods regarding the re-scheduling of codeine
Extensive public consultation is a critical and legislated component of the process and is associated with scheduling decisions and proposals that would change the Poisons Standard.
If a scheduling proposal is referred to an Advisory Committee then there will be two public consultation periods with invitations announced on the TGA website: a pre-meeting public consultation period and an interim decision public consultation period. The pre-meeting consultation period invites public submissions prior to the Advisory Committee meeting where they are considered by the Advisory Committee. Once the delegate makes an interim decision, this is published on the TGA website, and further public submissions are invited during the interim decision consultation period.
The public consultation process for codeine included an additional public consultation step in December 2015, following public feedback on the interim decision. This allowed for a more thorough consideration of the numerous submissions and broader implications to current products on the market. As part of the additional public consultation period, submitters were asked to comment on other options such as a reduction in pack size and the inclusion of a warning statement on the packaging.
Figure 6 compares the normal public consultation process (on the left) and the one that occurred for codeine (on the right), and provides a timeline of where the consultation periods fit in with the major codeine re-scheduling decision points.
Figure 6: Public consultation process for codeine and the timeline of major decision points
Left, normal consultation process; right, public consultation periods
Pre-meeting (July 2015 ACMS meeting) public consultation
On 1 April 2015, under subsection 42ZCZK/42ZCZL of the Therapeutic Goods Regulations 1990 (the Regulations), the delegate published a pre-meeting public notice on the TGA website which specified the proposed amendments to the current Poisons Standard and invited public comment. The proposed amendments referred to the ACMS by the medicines scheduling delegate for codeine were:
- To delete the Schedule 3 entry for codeine, and re-schedule the current Schedule 3 codeine entry to Schedule 4 due to potential issues of morbidity, toxicity and dependence.
- Consideration may be given as to whether all current Schedule 3 preparations should be re-scheduled to Schedule 4, or whether any re-scheduling to Schedule 4 should only apply to combination analgesic products containing codeine.
- Consideration may be given as to whether the Schedule 2 entry for codeine should also be amended.
The above amendments were proposed in response to public applications received by the delegate for medicines scheduling to to up-schedule products containing codeine to become prescription-only medicines (Schedule 4).
As outlined in the Regulations, this pre-meeting notice specified that these proposed amendments would be referred for scheduling advice to the ACMS at the July 2015 meeting. The ACMS comprises independent experts as well as state and territory representatives who provide advice to the medicines scheduling delegate.
The pre-meeting consultation period was open for public comment for 20 business days and closed on 7 May 2015. During this time the TGA received 60 pre-meeting public submissions for codeine. Of these, 29 submissions supported the proposal to up-schedule codeine products to Schedule 4. There were 25 submissions that opposed the proposal. Six (6) submissions did not state whether or not they supported the proposal. All of the pre-meeting public submissions were considered by the ACMS at the 'July 2015' meeting (which was held in early August 2015). Also considered was the the advice of an independent pain specialist who was contracted to evaluate the re-scheduling proposal. The expert supported the proposal to up-schedule Schedule 2 and Schedule 3 codeine products to Schedule 4. The ACMS advice to the delegate was to delete the current Schedule 2 and 3 entries for codeine and amend the current Schedule 4 and 8 entries to reflect this change.
Interim decision public consultation
On 1 October 2015, under subsection 42ZCZP/42ZCZQ of the Regulations, the TGA website published the delegate's interim decision and the reasons for the decision. Further submissions were also invited from the applicants and parties who made valid pre-meeting submissions. The delegate's interim decision was to delete the current Schedule 2 and 3 entries for codeine and amend the current Schedule 4 and 8 entries to reflect this change. The reasons for this interim decision to up-schedule are provided in the published delegate's interim decision and outlined in the section titled 'What is the problem?'.
The inivitation to make submissions was open for 10 business days and closed on 15 October 2015 . During this interim decision consultation period the TGA received 127 public submissions. Of these, 14 supported the decision and 113 opposed the decision. The reasons were similar to the pre-meeting submissions. It was noted that comments made during the interim decision consultation period would be taken into consideration in any final decision on any implementation date.
Additional consultation period
In order to give due consideration to the submissions received in the interim decision public consultation period and to seek further advice from the ACMS at its March 2016 meeting, the medicines scheduling delegate on 18 November 2015 deferred a final decision on the proposed codeine re-scheduling.
The TGA then sought further advice and public comment on several options for codeine re-scheduling via an additional consultation period that was open from 10 December 2015 through 29 January 2016. The scheduling options included:
Schedule 2 (cough and cold medicine preparations):
- Proposal to amend the Schedule 2 entry to reduce the pack size to not more than 3 days' supply and include a label warning that codeine can cause addiction, OR
- Proposal to up-schedule the Schedule 2 entry to Schedule 3 and reduce the pack size to not more than 3 days' supply and include a label warning that codeine can cause addiction, OR
- Retain the interim decision to up-schedule to Schedule 4.
Schedule 3 (including, but not limited to codeine-containing analgesics):
- Proposal to amend the Schedule 3 entry to reduce the pack size to not more than 3 days' supply and include a label warning that codeine can cause addiction, OR
- Retain the interim decision to up-schedule to Schedule 4.
The medicines scheduling delegate outlined a provision of the re-scheduling options listed above, that they were not precluded from considering alternative scheduling options.
The TGA received 49 public submissions from this additional consultation. Roughly equal numbers of submissions were received either for or against the interim decision. Many submissions were copies of previous submissions.
Summary of public submissions
Public submissions received by TGA in response to all three consultations were from the following groups of stakeholders: consumers, industry, peak bodies, healthcare professionals, and state and territory government bodies.
The following section outlines the main points from all public submissions and stakeholder categories. These have been separated into submissions either supporting or opposing the up-scheduling.
Public submissions supporting up-scheduling
Of the 60 pre-meeting public submissions for codeine, 29 supported the proposal to up-schedule codeine products to Schedule 4. Of the 127 public submission received following the interim decision, 14 supported the decision. Of the 49 public submissions received from the additional consultation in December 2015, roughly half of the submissions supported the interim decision. When comments were made regarding improved labelling, all submissions supported this measure. The majority of comments regarding reducing pack size were also supportive.
Consumers who supported up-scheduling often referred to relatives or friends who were addicted to codeine and that codeine was too easy to access and contributed to illnesses. There were numerous personal accounts of dependence, addiction and side effects, increasing over the past 10 years. It was suggested by some consumers that up-scheduling would reduce the potential for abuse, and that preventing easy access to an opioid would require patients to seek other low risk medications or get further medical advice. In addition, they felt that up-scheduling would reduce the potential for harm, particularly from complications due to overdose in codeine products combined with paracetamol or ibuprofen. Some felt that it was not currently possible for pharmacists to monitor and control safe use of low-dose codeine. Some consumers felt that real time monitoring would not be effective, would be costly and clumsy, and could involve risks to pharmacy staff who refuse to supply codeine.
Most members of the pharmaceutical industry were opposed to up-scheduling codeine to a prescription-only medicine. An exception was one sponsor who did not manufacture a codeine-containing product. This company supported up-scheduling.
Healthcare professionals and related peak bodies
Most healthcare professionals - including GPs, pain specialists, addiction specialists, psychiatrists, anaesthetists, hospital pharmacists, and their relevant representative medical colleges and societies - supported up-scheduling codeine to a prescription-only medicine. This was due to numerous studies and clinical evidence showing misuse and abuse related to codeine posed a significant risk to public health. If ease of access to an opioid was restricted, patients would seek other low risk medications and/or further medical advice. They stated that codeine-related patient numbers were increasing, with intensive and long-term treatment management being required. Further discussion points provided by healthcare professionals and related peak bodies included the inter-individual variation to codeine metabolism causing increased risks, and the known toxic side-effects routinely observed in hospitals. There was evidence of substantial risks to addiction and toxicity associated with ibuprofen or paracetamol in combination products. Many agreed that OTC codeine combination products do not meet the standards required to achieve acceptable safety and efficacy. Some stated that codeine doses are sub-therapeutic in OTC codeine combination products, and there was a lack of data to support its efficacy as an effective analgesic or cough suppressant.
Public submissions opposing up-scheduling
Of the 60 pre-meeting public submissions for codeine, 25 opposed the proposal to up-schedule codeine products to Schedule 4. Of the 127 public submission received following the interim decision, 113 opposed the decision. Of the 49 public submissions received from the additional consultation in December 2015, roughly half of the submissions opposed the interim decision.
Over 70% of consumers raised the potential of additional financial burden to both patients and Medicare from the costs of increased GP visits if codeine were to only be available by prescription. Other common points raised by roughly 25% of consumers were that combination low-dose opioid pain relief was believed to be more effective than non-opioid alternatives, that they were able to self-manage their own pain relief, that up-secheduling would prevent them from accessing adequate pain relief, and that RTM and education would provide better regulation than up-scheduling. There were also a few concerns that people in rural areas may not be able to quickly access a GP if codeine becomes prescription-only.
Industry and related peak bodies
Most pharmaceutical companies opposed the up-scheduling, as did the Pharmacy Guild of Australia, the Pharmaceutical Society of Australia, Australian Self-Medicating Industry, and some other consumer groups. Most discussed that a reduction in pack size and mandatory warning statements regarding the potential for dependence would be more acceptable. They also believed that pharmacists are able to discuss alternative treatments and manage risks with codeine, or that a national, RTM system is preferred. Some thought that there was insufficient evidence that the morbidity issues result from cold and flu preparations.
Some healthcare professionals suggested that re-scheduling may result in under-treatment and over-investigation, and that re-scheduling may cause at-risk patients to turn to alternative drugs for pain relief, such as alcohol, cannabis, psychostimulants; these alternatives were reasoned to have other risks. They also pointed to research suggesting that codeine is effective for acute pain, thus meeting the claim of short term relief.
General practitioner considerations
To better understand the issues and implications of codeine re-scheduling for Australian general practitioners (GP) and general medical practices, a meeting was conducted with the Australian Medical Association (AMA).
The expected increase in the number of patients presenting to GP practices requesting a script for codeine as a result of the re-scheduling of codeine-containing products to Schedule 4 was welcomed by GPs. Firstly, the initial increase in previously self-managed chronic pain sufferers presenting to their GP will result in better diagnosis and condition management by GPs. For example, headaches are often misdiagnosed by patients as migraines and subsequently mistakenly self-treated with analgesics. However headaches may be a symptom of more complex issues originating from the eyes, neck and/or back and may even be a result in changes in blood pressure. These types of conditions can be identified and treated more effectively by a GP through appropriate pharmacological options, and in some cases more effective alternative non-pharmacological options such as physiotherapy, osteopathy and/or exercise. Secondly, previously undiagnosed and unaccounted for dependent users, unaware of their codeine dependency or too embarrassed to seek help, will have to see a GP to obtain codeine and therefore receive the help they need to overcome their addiction. The behaviour of chronic pain sufferers and codeine dependent users are expected to drastically change as a result of GP consultation.
Many GPs are well-informed regarding the risk versus benefit of codeine-containing drugs and are able to restrict the potential for overdose or daily abuse by limiting the number of daily tablets dispensed or the number of script repeats. This promotes ongoing GP management to ensure that the course of treatment is still appropriate or to ascertain any health complications regarding the drug. It was proposed however, that some GPs, without awareness of the regulatory change, will prescribe high dose codeine-containing products in order to reduce the dose of paracetamol ingested by the patient, without undertaking a full assessment or further investigation into the cause of the patient's pain. This will have to be managed through an appropriate GP education program.
Primary Health Networks are currently developing pathways and decision assistance tools for chronic pain condition management. These tools will enable GPs to better diagnose and manage chronic pain and if necessary, refer patients to pain management clinics. However, this is where the bottleneck currently lies with current access to these facilities involving long waiting periods. The model of pain clinics will have to change to accommodate the re-scheduling of codeine-containing products to involve more outreach programs and communication with GPs.
In addition to issues with pain management clinic infrastructure, another concern from a GP perspective is the lack of suitable alternatives to OTC codeine-containing analgesics for the over- 65 population. Non-steroidal anti-inflammatory drugs (NSAIDS, such as ibuprofen), a commonly used alternative to codeine-containing products, are not recommended for use in patients over the age of 65 due to the increased risks of cardiovascular disease, renal impairment and the increased risk of gastrointestinal ulcers.
Targeted consultations with industry and peak bodies
To help support the final decision relating to the re-scheduling of codeine, this RIS is modelling the economic, social and regulatory impacts of the codeine scheduling options. KPMG were contracted to undertake the economic modelling and financial quantification of the regulatory impact of the proposed changes to codeine scheduling. The development of the regulatory cost estimates was informed by targeted consultations with sponsors who currently produce codeine-based products in the OTC market. The target sponsors were Sandoz Pty Ltd, Sanofi-Aventis Australia Pty Ltd, GlaxoSmithKline Consumer Healthcare Pty Ltd, Soul Pattinson Manufacturing Pty Ltd and Johnson & Johnson Pacific. These companies occupy both distinct and overlapping segments of the OTC and prescription market and were able to provide a range of perspectives given the different incentives and risks that are intrinsic to their business models.
In preparation for these interviews, all sponsors were provided with background material and a list of questions for discussion (Appendix A). The interviews were structured around product strategy, market response, labelling, packaging, updated listing and regulatory approvals, and implementation. Industry input contributed to the development of the regulatory costing model, allowed for the testing of baseline assumptions and gave some insight into anticipated supply and demand behaviour of market participants in response to the re-scheduling options.
Interviews with industry
Five pharmaceutical companies that currently sponsor codeine-containing products on the Australian Register of Therapeutic Goods (ARTG) were interviewed:
- GlaxoSmithKline Consumer Healthcare Pty Ltd - a major provider of Schedule 2 and Schedule 3 medicines containing codeine.
- Johnson & Johnson Pacific - a major provider of Schedule 2 and Schedule 3 medicines containing codeine.
- Sandoz Pty Ltd - a major provider of Schedule 2 and Schedule 3 (OTC) medicines containing codeine.
- Sanofi-Aventis Australia Pty Ltd - a major provider of Schedule 3 (OTC) and Schedule 4 (prescription only) medicines containing codeine.
- Soul Pattinson Manufacturing Pty Ltd - a major provider of Schedule 2 and Schedule 3 medicines containing codeine.
In preparation for these interviews, all sponsors were provided with background material and a list of questions for discussion (Appendix A). Industry input contributed to the development of the regulatory costing model, allowed for the testing of baseline assumptions and gave some insight into anticipated supply and demand behaviour of market participants in response to the re-scheduling options.
Interviews with peak bodies
Further interviews were conducted with representatives from peak bodies to inform the development of the economic and social model:
- Australian Medical Association (AMA) - as the peak body representing registered medical practitioners and medical students of Australia;
- Pharmaceutical Society of Australia (PSA) - as the peak body representing pharmacists in Australia;
- Australian Self Medication Industry (ASMI) - as the peak body representing companies involved in the manufacture and distribution of consumer healthcare products in Australia; and
- Pharmacy Guild of Australia (PGA) – as the peak body representing pharmacists and pharmacies in Australia.
A high level summary of industry responses (including peak bodies) are provided here without direct attribution to specific stakeholders. This is intended to provide an overall picture of the feedback and the key themes that emerged from the meetings and in which informed the modelling.
Topic 1 - Product strategy
Sponsors were asked about how they would respond to up-scheduling decisions and what factors would be considered in determining their product strategy. There was a high level of concern by Schedule 2 and Schedule 3 sponsors about the impact of up-scheduling on their business. Sponsors identified a number of issues that undermined the commercial viability of up-scheduled codeine products. These issues were fundamentally connected to the different distribution and market access models associated with Schedule 3 and Schedule 4 arrangements, and uncertainty about the level of demand for lower dosage codeine products given the current prescribing habits of GPs.
Key points were:
- Schedule 2 sponsors are unlikely to migrate these products to Schedule 4. It is likely that most Schedule 2 sponsors will migrate Schedule 2 products to Schedule 3, and would rationalise their product portfolio with generic brands.
- Schedule 3 sponsors would evaluate the commercial viability of moving these products to Schedule 4; however, this would be largely contingent on their expectations about demand and confidence that GPs would change their prescribing habits to account for different dosage options.
- Sponsors with branded products highlighted concerns about the impact of discontinuing products on brand equity and the regulatory barriers to redeploying or reformulating well known and trusted brands which are a source of value for these companies.
Topic 2 - Market response
Sponsors were asked to provide views on what impact the different options would have on the behavior of customers (across different segments) and the level of demand and substitution they would expect to see in the market.
Key themes were as follows:
- The introduction of warning labels and reduced pack sizes would slightly reduce overall revenue; however the overall demand for codeine would largely remain.
- The up-scheduling of codeine from Schedule 2 to Schedule 3 would reduce demand but there would still be a market for codeine-based cough and cold products. However, consumers would be presented with less range and choice as products move behind the counter. This would necessitate some degree of product rationalization.
- The up-scheduling of codeine from Schedule 2 to Schedule 4 would effectively see these product lines discontinued.
- The up-scheduling of codeine from Schedule 3 to Schedule 4 would reduce overall demand for medium dosage codeine products, however a sizable segment of these existing customers would continue to seek out codeine products and visit a GP to obtain a prescription. Sponsors all considered it likely that these consumers would visit their GP and receive access to higher dosage products with larger pack sizes which could lead to perverse outcomes.
- The Schedule 3 market is essentially entirely made up of consumers. Hospitals and other institutions do not bulk purchase OTC codeine products (tending to use paracetamol or move to higher strength opioids).
Topic 3 – Reduced pack size
Sponsors were asked to comment on whether they have products or manufacturing arrangements that would readily accommodate the requirements of a 3-day pack (both in terms of the outer pack and the inner blister packs). There was a mixed response regarding this question, with about half of the sponsors indicating they already produced a 3-day pack or had production lines that could be used to do so, and thus they could accommodate this at essentially no cost. Others would incur costs for re-tooling machinery to modify the depth of the outer pack or the length of the inner blister pack.
The sponsors interviewed stated that costs appeared to depend on whether the manufacturing was done in Australia or overseas. Re-tooling in Australia is more expensive (and potentially cost prohibitive) and ranges from between $30,000 to $150,000. Re-tooling overseas is cheaper and ranges from between $10,000 to $30,000. The sponsors also expressed an opinion that implementation in local facilities could be executed more quickly (6 months) whilst changes to overseas facilities would take longer (12 months).
Topic 4 – New warning labels
Sponsors were asked to describe the steps involved in adding new labels, and the costs associated with these steps. Broadly, the steps identified were the development of artwork and design, internal review, quality assurance and implementation. The range of costs provided by sponsors was between $2,000 and $6,500.
Sponsors noted they would look for opportunities to roll out label updates into others which were already in the pipeline. Updates would typically occur once every 3 years.
Implementation timeframes are between 6 and 12 months. Similar to packaging, overseas production arrangements required longer lead-times as there is less flexibility in scheduling updates into manufacturing change windows.
Topic 5 – Updated listings
Sponsors were asked to comment on time or cost of regulatory forms and other compliance processes connected to the various options. Key points were:
- C1/C2 forms were noted as relatively straight forward. With sponsors indicating time required to complete, undertake internal review and submit forms being between 4 – 10 hours of effort.
- Sponsors indicated updating Product Information (PI)/Consumer Medicines Information (CMI) documents would also be straightforward. In the event a new PI/CMI had to be created (such as Schedule 2 up-scheduling to Schedule 3) sponsors would not seek to create one from scratch but leverage a model PI already being used in that schedule.
- Sponsors did not anticipate up-scheduling to Schedule 4 (if they were currently in Schedule 2 or Schedule 3) would cause any difficulties with respect to GMP conformity. The sponsors consulted were all confident their facilities were GMP compliant and also noted those facilities were already manufacturing other Schedule 4 products.
- In their responses, sponsors indicated that based on precedent, they would expect the TGA to upgrade Schedule 2 and Schedule 3 products into Schedule 4. They cited the standard registration process for a prescription medicine as material cost and time delay that could require up to 24 months subject to the scope of the application requirements.
Topic 6 – Implementation timeframes
Implementation timeframes were discussed with sponsors throughout each of the topics to understand the minimum and ideal timeframes connected with different change processes. The purpose of this topic was to understand any other implementation considerations pertinent to industry.
Several sponsors expressed concerns about the lack of certainty concerning the implementation timeline and arrangements that would accompany a decision to up-schedule. They noted the critical importance of implementation timeframes in enabling business to reposition themselves in the event of an adverse outcome. They also noted that a short implementation timeframe would potentially increase costs and make it difficult to reposition themselves in the market without significant losses in revenue. In this respect, sponsors emphasized the engagement of the TGA would be critical towards assisting their planning.
Broadly, sponsors indicated a reasonable end-to-end implementation timeframe would, at a minimum, be between 18 to 24 months. However, sponsors noted their concerns that an 18 to 24 month timeframe may be perceived as being at odds with the safety/risk rationale of the interim decision and that the TGA would be presented with a moral dilemma in balancing the two.
Other key themes were as follows:
- Pharmacies generally hold between 1 to 2 -month worth of stock depending on their location
- Most manufacturers do not hold large amounts of produced stock but make to order. However, they do make bulk purchases of components and materials and these can take between 4 and 9 months to turn over
- Shelf life of codeine products is 24 months. Sponsors were concerned a short implementation timeframe may require some residual products to be recalled from shelves which would be a costly exercise and involve reverse logistics
- The minimum timeframes to comply with an up-scheduling decision appears to be around 9 months. However sponsors noted this assumes that there is no business case development or evaluation of commercial viability to up-schedule which they considered to be unreasonable. They further expressed a view that a longer timeframe is needed to enable this to be undertaken in an orderly way, and
- Sponsors indicated time is also needed for GPs to be educated about the changes (in the event of an up-scheduling) to ensure their prescribing habits adapt to the new situation, and that medium dosage codeine products (at 12.5mg) are prescribed when appropriate. Sponsors also sought clarity as to whether the government or industry would be expected to fund the costs of GP education.