As part of our IPU Review special this month on medicine shortages, we asked a number of key stakeholders the same questions in relation to medicine shortages. The replies we received are printed over the following pages.
In addition to the stakeholders who provided their views across the following pages, we also asked a different set of questions, specifically related to patients’ experiences of medicine shortages, and received the following replies from Patients for Patient Safety. We are including the patient’s perspective as the starting point for stakeholder engagement.
If you have had the experience of one or more of your medications being short then you may consider it bad and possibly getting worse. Or all your medications may be in good supply. There is no one general situation that speaks of the experience of all patients. Therefore, some patients have not had any problems with shortages and others have had occasional or quite a few. It is a spectrum.
For myself and for those in my family it has been a little worse. Fybogel unavailable, then available only OTC but not on prescription, and now gone again. Ryaltris nasal spray gone as we come into the hay fever season.
As a volunteer group our ability to undertake change action is limited, but rather we seek to influence in talks, in meetings and where opportunities present such as this article. But as time goes on we would hope to influence more at policy and clinical level.
Personally, I do understand most of what happens to resolve the issue but some others may not. Pharmacy staff usually share what they are doing, and it encourages patients to know that all reasonable steps are being taken. But the level of work involved may not be fully understood.
So, I guess that patients understand that the best is being done for them even if they haven’t all the detail. We see the tip of the iceberg. But in general, pharmacists do not complain to patients about their increased workload, but rather seek to ease any concerns patients may have.
My general understanding of the allocation model is that where supplies are limited each pharmacy receives a set amount or allocation regardless of their actual requirements. The allocation is likely to be less than the requirement, but I cannot say whether this can be significantly so or not. I am not sure how many patients understand that this can happen; my personal involvement in the matter has probably left me a little more informed than some others.
Ideally patients should not require EMP’s unless the circumstances are unusual. They should be made aware that it is an EMP and the implication of that explained. If the product is available in a licensed capacity in another comparable jurisdiction, then this information may provide some reassurance that a degree is assessment has been undertaken.
Advice for pharmacists is a brave question! That can vary from the ideal to the practical depending on the humour. Seriously though I do have some thoughts, which I hope that you find reasonable. In most pharmacies, patients can either be familiar or not. For those who rarely have need of medication or are only passing through, you can only communicate the situation as clearly as possible with a reassurance that you will endeavour to find a viable solution usually in consultation with your GP.
Where I personally think an opportunity exists to improve care is with established patients. Within this group I am assuming that most have long-term treatment, and many may be on polypharmacy, and some are known to have difficulty managing their medication. With the vulnerable patients I would seek to minimise any change, if possible, by reserving the allocation stocks for them. However, if this not feasible then I wouldn’t wait till the prescription is due and I would contact the GP in advance for an alternative. In addition, I would then contact the patient to highlight that this has been done. Pharmacists generally know their regular patients well and most likely could identify those who could benefit most from a proactive rather than a reactive approach.
I know that this sounds like a lot of work, but it could reduce a lot of worry for patients already under pressure. But it may not be much additional work in fact — the same steps are often taken anyway after the prescription is due.
To be honest I think there should also be a national agreed substitution approved to minimise duplication of work by GP’s and pharmacists. This should be information that is readily available to all including patients.
Over the following pages, we provide the responses received from the Department of Health, the HPRA, Medicines for Ireland and Azure Pharmaceuticals on medicines shortages, to a series of set questions. The Irish Pharmaceutical Healthcare Association also provided a statement, which is printed at the close of the questions.
1. The IPU Shortages survey for 2024 highlighted that 57 per cent of members had encountered 41 or more shortages over the last four months, this was a slight reduction that the 60 per cent of members in last year’s survey. What is the view of your organisation on the medicine shortage situation this year, has the situation remained static, improved or got worse for Irish patients?
The Department of Health: Medicine shortages are, unfortunately, a feature of modern health systems worldwide and a global health problem. The causes of such supply issues are multifaceted, and these can range from supply chain disruptions due to pandemics and geopolitical events, to increases in global demand.
The Department recognises that shortages of medicines at a pharmacy level can cause concern for patients and healthcare providers alike. Issues surrounding security of supply of medicinal products have become increasingly well characterised, and thusly have become an increased area of focus for stakeholders of the health service, and a priority for the Minister for Health.
The Health Products Regulatory Authority (Ellen McGrath, Medicines Shortages and Borderline Classification Manager, HPRA): Shortages are a global issue experienced by all countries regardless of size or economic status. Their incidence is increasing. Taking 2023 as a snapshot, all medicines regulatory agencies at the global level reported sharp increases in shortages relative to previous years.
In the first quarter of 2024 the number of shortages notified to the HPRA (Jan-March 2024 inclusive) is lower than the total number of shortages notified to the HPRA in the same period last year (318 notifications in Q1 2024 vs 382 notifications in Q1 2023). While this represents a numerical improvement from last year, each notified shortage does not represent an absolute risk to patient. It is a signal or risk factor which the HPRA, in association with other parties across the health system, use to monitor overall national supply of a single therapy. Drawing particular significance from an absolute number of shortages notified and listed on the HPRA website does not indicate risk to patients, given that alternative treatments are generally available to ensure continuity of care.
Given the above contextual factors the HPRA considers that managing and mitigating shortages will remain a high priority this year, with efforts that are continuing to improve overall supply and availability of medicines, predominantly driven through the national shortages framework operated by the HPRA as well as HPRA contributions to the European initiatives in place to address the issue of medicine shortages.
Medicines for Ireland (Paul Neill, Chair): At present, one of the most pressing issues identified by Medicines for Ireland (MFI) members is the complexity of the healthcare system. This is having a direct impact on the shortages of medicines. Existing pricing policies, which primarily focuses on continual reductions in medicine prices, have also led to market concentration, increasing shortages of essential medications and greater dependence on exempt medicinal products. All of this adds an additional burden on certain elements of the supply chain, such as pharmacists who are tasked with finding alternative medicines for patients.
While the situation has not got worse, it remains at an unacceptable level and is volatile, and we often see peaks at critical times such as the winter months when hospitals and healthcare professionals are already at full capacity.
MFI is of the view that relevant stakeholders do not yet have a comprehensive understanding of the global and local generics, biosimilar and value-added medicines environment and its associated challenges in Ireland.
This underscores the need for further investigation and strategic planning. MFI wishes to develop a greater understanding of these challenges among its key stakeholders through closer engagement with policymakers, regulators, and partners in the supply chain to demonstrate the complexity of the eco-system in which generic manufacturers are operating and thus create the optimum conditions for the state, industry and for Irish patients.
Azure Pharmaceuticals (Sandra Gannon, Managing Director): Azure tracks the level of out-of-stock medicines in Ireland on a regular basis. The reconfigured HPRA shortages report would appear to indicate that medicine shortages have stabilised or declined. However, in September 2023 a change was made to the method of reporting medicine shortages and only those that are deemed to be medium or high impact are reported. The decision to stratify the impact of a shortage and whether it is reportable is often being made by the Marketing Authorisation Holder (MAH), and as a result, many multi-source generic shortages are not being reported in the published list. MAHs may decide their market share for an out-of-stock medicine is not sufficiently large as to create a market shortage, and therefore will deem their shortage as low impact. The problem with this system is that knock-on effects of one small shortage can accumulate into a much larger problem in the following months. Any shortage can also signify upstream issues, such as global API shortages or Nitrosamine content issues, that may have future consequences. We believe that every shortage, no matter how low-level, should be reported transparently as it will have a consequence for patients, healthcare professional and payers. The over-reliance on EMPs by the sector, has also papered over the underlying level of shortages and discontinuations in the off-patent segment of the market while continuing to put pharmacists in a very difficult position.
2. What proactive measures are you as an organisation seeking and helping to operationalise to help tackle and reduce this chronic issue?
Department of Health: The Department of Health engages several national mechanisms to reduce the number of and mitigate the impact of medicines shortages:
Additionally, the Department is engaged with numerous global and European initiatives aimed at targeting the occurrence of medicines shortages and ensuring security of medicines supply. This includes engagement with the European Commission on their proposed revision to the general pharmaceutical legislation.
HPRA: When the HPRA receives a notification, our role is to coordinate a multistakeholder response via the National Medicines Shortages Framework (‘the framework’). Participants in the framework include the Department of Health, the HSE Corporate Pharmaceutical Unit (CPU), industry and healthcare professionals. The framework has been in place since 2018 when the Department requested that the HPRA assume responsibility for its coordination.
Since its inception, the framework has been of enormous benefit nationally. It has served to avoid the occurrence of potential medicine shortages and, where they have occurred, ensured appropriate mitigation is in place.
The notification of possible shortages to the HPRA is the basis for triggering the framework and the associated coordinated multi-stakeholder response as required, including preventative or mitigation strategies. The proximity of the notification timing to the actual shortage occurrence reduces the ability to identify and implement actions to prevent the shortage from occurring. MAHs and wholesale distributors, in particular, are key stakeholders in the supply chain that have more visibility of stock levels than others. These stakeholders must report potential shortages at an early stage. If action is taken at an early stage to avoid the shortage or any impact on patients and healthcare professionals, then no other action is required under the framework.
There have also been developments at central EU level to ensure greater coordination and consistency in actions taken by member states to address medicines shortages. Much of this has been facilitated through legislation that took effect in March 2022, expanding the European Medicines Agency (EMA) remit. The EMA now has a formal EU role in preparing for and managing crisis situations involving medicines. This includes monitoring medicine shortages that might lead to a crisis and activities relating to medicines considered critical to a crisis. Enhanced European coordination and the expanded role of the EMA in medicines availability and shortages are welcomed. The HPRA is committed to continuing its active involvement at European level to maximise the effectiveness of this work. Specific initiatives, such as the introduction of the Union list of critical medicines and the requirements under the proposed new European pharmaceutical legislation for an MAH to have in place shortage prevention plans (‘SPP’) are anticipated to further improve supply chain resilience and promote continuity of supply.
Medicines for Ireland: To address the industry’s challenges and provide solutions to tackle shortages, MFI is dedicated to leading the development of research and engaging with the Department of Health, the HSE, the Health Protection and Regulatory Agency, as well as a wide range of political and departmental stakeholders.
In addition to this, MFI is committed to working in collaboration with patient representatives, conducting and publishing research into the impact of shortages and the issues causing them and advocating for dynamic policies that foster competition. It should also be noted that a greater penetration and uptake of generic, biosimilar and value added medicines offers a pathway to redirect scarce resources within the healthcare system, thereby alleviating strains.
MFI member companies proactively engage with the HPRA’s framework for handling medicine shortages, providing as much advance notice as possible and shortage mitigation measures where available and appropriate.
Azure: Azure is strategically invested in continuing to focus on bringing solutions for medicine shortages to the Irish market in the form of licensing medicines that are only available from unlicensed sources and also bringing a second supply for medicines that are single source. We are constantly working to ensure that the licensing for such medicines is given priority by the regulator and that the reimbursement price paid for such medicines is a fair reflection of the costs involved in bringing these medicines to market. We are also working with companies that have no commercial structures in Ireland or deem the market too small to be of interest, in order to secure licensing and supply for Irish patients. We continue to build-up a strong stock holding to ensure that we can meet forecasted demand for the next nine months which often allows us to cover shortages that are encountered by competitors.
3. The survey highlighted that in pharmacists’ opinion the main cause for a medicine shortage at a pharmacy level was due to the medicine being on allocation, with national pricing policies and manufacturing disruptions being the third. What is the view of your organisation on the current model of allocation, and do you have any views on how this system could be improved to ensure equity of supply to Irish patients?
Department of Health: It is important to note that the existing model of allocation is utilised, 1) during periods of limited supply to, 2) ensure equity of access. As outlined in previous responses, the causes of medicinal product shortages are multifaceted. Ireland has a variety of mechanisms, both existing and in development, to mitigate the impact and prevent the occurrence of shortages.
The HPRA maintains an up-to-date list of shortages on their website Shortages List (hpra.ie). Each shortage is accompanied by a reason for the shortage and an expected date of supply return.
HPRA: A medicine shortage can occur for many reasons. Each shortage represents an individual set of circumstances. From industry information received by the HPRA, we know that:
Allocations are considered necessary in justified cases, to prevent shortages occurring, and are not a recognised, or known cause for a shortage in and of itself. The HPRA also engages with MAHs and wholesalers, where signals of supply difficulties emerge from pharmacies or hospitals, to ensure that any allocation in place is being operated for supply that is sufficient to meet overall demand, and not being used as a measure to manage a shortage in supply available. Allocations are considered to help ensure continuity of supply and equitable distribution of stock to Irish patients. This measure should be justified (i.e. only in cases where there is a risk of a shortage occurring from uncontrolled distribution) and ideally will represent a minimum level of administrative burden to operate, for all parties involved in the supply chain. The HPRA encourages contacts be made readily available to pharmacists experiencing any problems with an allocation system, in every case that it represents a genuine barrier to supplying an individual patient with their medicines.
Medicines for Ireland: Enabling appropriate levels of supply chain transparency is critical in facilitating proactive measures against shortages and ensuring security of supply for Irish patients. Regarding national pricing policies, applying external reference pricing to generic medicines can threaten competition and sustainability in the market.
In some cases, the prices of generic medicines go below what is commercially sustainable for generic pharmaceutical manufacturers, which leads to the withdrawal of medicines. Furthermore, Medicines for Europe points out that this has been confirmed in the European Commission study on medicine shortages, demonstrating that 90 per cent of withdrawals are linked to this commercial unattractiveness.
This can be deleterious to the generic medicines industry and also for the quality of healthcare, as these artificially low prices might endanger the security and continuity of supply, hampering the access and affordability objectives of healthcare systems and has a negative impact on Irish patients accessing medicines.
It should be noted that allocation of medicines are not per se the cause of a medicines shortage, but rather are often the result of medicines shortages. Medicines for Ireland are focused on collaborating with other stakeholders so that shortages are minimised, reducing the number of medicines on allocation.
Azure: Allocations are put in place to manage two issues: firstly, stockpiling where the medicine is deemed a supply risk or, secondly, where there is a risk of export from Ireland to higher priced markets would leave a market shortage. While it may not be ideal to manage genuine demand, it is often the only tool available to MAHs and wholesalers to manage these risks. In the case of national pricing policies, Ireland needs to reflect that as a small size market and now the only market with English language packs, it is at risk of losing more supplies. We have put forward proposals on how these challenges can be addressed.
4. 98 per cent of pharmacists surveyed indicated that their dispensing of Exempt Medicinal Products had increased versus the previous year, this statistic has been increasing yearly since the survey began in 2017. What is the view of your organisation as to the drivers of this trend?
Department of Health: Schedule 1 of the Medicinal Products (Control of Placing on the Market) Regulations 2007 includes an exemption which enables practitioners to prescribe a medicine as an exempt medicinal product (EMP) under that practitioner’s direct responsibility, in order to fulfil the special needs of that specific patient.
An EMP may not be prescribed or supplied in situations where an authorised or registered equivalent (i.e. same active substance(s), strength and dosage form) is available in Ireland.
If a valid prescription is issued for an EMP in line with the above Regulations, an appropriately authorised wholesaler, can source that product from another market for supply to the patient via their pharmacy in line with that prescription.
It would be inappropriate to postulate reasons for a reported increase in dispensing of EMPs without further information regarding the indications these EMPs are prescribed to treat.
HPRA: According to European and Irish legislation, medicinal products must undergo authorisation procedures before marketing. However, in Ireland, specific provisions are in place that enable supply outside of this authorisation process, which are:
The HPRA is unable to comment on a trend that is based on subjectively based observations of supply of unlicensed medicines as expressed within this specific survey of community pharmacies/community pharmacists. The HPRA does however operate a notification system, which is mainly intended to put appropriate risk-mitigating measures (such as a product recall) in place, in order to enhance protection of patients in receipt of EMPs. The HPRA is currently considering the empirical evidence of EMP utilisation available to it, in order to promote and encourage manufacturers to market licensed alternatives. The HPRA can apply regulatory flexibility, in as much as possible and appropriate, for the authorisation of these medicines, such as accepting dual pack labelled products with other EU Member States.
Medicines for Ireland: The relatively small Irish market and restrictive pricing policies are likely to play a significant role in driving the growing reliance on exempt medicinal products. As a small island nation on the edge of Europe, policies such as mandatory price discounts and external reference pricing can make the Irish market less attractive for pharmaceutical companies to apply to licence medicines in certain categories. In addition, favourable pricing policies should be put in place to facilitate the launch of licenced alternatives where there are only exempt medicinal products available to patients. Considering the market size is not going to change dramatically, MFI will continue to engage with the Department of Health, HSE, HPRA and CPU to encourage them to use the levers that are available to them in relation to pricing policies to enhance competitiveness in the off-patent market.
Azure: EMPs are being used prolifically as more commercial organisations are seeing their value through higher pricing opportunities and a lack of regulation and oversight. The supply of EMPs is also now being employed by MAHs to cover their inability to supply Irish licensed pack and they can often access stock from their continental or UK affiliates. Long after licensed supply resumes in the market, EMPs continue to be used without checks on the justification for their use. It is also clear that patients are not being informed that an EMP is being dispensed to replace the licensed version of their prescription medicine. The ongoing risk of falsified medicine entering the supply chain via the EMP route is significantly greater now than ever before despite the introduction of FMD legislation. The fact that the HSE has agreed long term pricing for EMPs, sometimes at a higher price point than that which is offered for the licensed version, is also making the supply of EMPs a lucrative and growing part of the market which is under-controlled and uncosted. Pharmacists are being put in a vulnerable position as a result of problems which are not of their making. It is high risk and unsustainable.
5. There is significant work on-going at a national and European level in relation to medicine shortage management. As an organisation, what pro-active measures in the management of shortages would you support being enabled in Ireland?
Department of Health: The Department of Health is actively engaged in a variety of fora at a European Level regarding the management of medicines shortages. For example, the Department of Health is the lead Government department in Ireland tasked with responding and engaging nationally and at EU level, as the pharmaceutical package proposal is negotiated by all EU-27 and progresses through the ordinary legislative process. The Minister for Health established the Cross Government and Cross Agency Pharmaceutical Strategy Working Group (PSWG) to support the development of Ireland’s response to the proposal from a national perspective and facilitate this position to be informed by a whole of Government view. Following the example of several Member States, the Department is introducing a reporting requirement for members of the medicines supply chain via the Health (Miscellaneous Provisions) Bill 2024, as detailed above, as well as a framework for Medicine Substitution Protocols (MSPs).
HPRA: The HPRA have indicated to the Department of Health its commitment to this endeavour, by signalling the availability of the additional resources in the Medicines Shortages and Borderline Classification (MSBC) team to work proactively with the Department, with the view to having tangible developments in this space. Current national legislative developments is considered by MSBC leads, to be supportive of these endeavours.
Enhanced European coordination and the expanded role of the EMA in medicines availability and shortages, the EU Pharmaceutical Strategy for Europe, resolutions of the European Council, and the proposed revision of pharmaceutical legislation are welcomed. These are hugely important to developing the European approach, strategically addressing challenges and driving consistency and harmonisation, particularly during crises. The HPRA is committed to continuing its active involvement at European level to maximise the effectiveness of this work.
Medicines for Ireland: Any medicine shortage management proposal should be aimed at addressing vulnerabilities in the global production chain by enhancing the efficiency and digitalisation of the medicines regulatory network.
MFI fully supports a risk-based strategy for shortage prevention plans (SPP), which would entail establishing a unified list of critical or essential medicines lacking alternatives. This approach would direct the attention of MAH’s and medicine agencies towards preventing and alleviating shortages, averting the generation of cumbersome reports and submissions that lack the necessary resources for review and processing.
Azure: It is difficult to see, at this stage, what impact the EU focus on medicine shortages as the main focus is on information gathering and sharing while Member States continue to take measures that sort out the issue in their own jurisdiction, sometimes at a cost to other members. For example, the recent German decision to stock-pile antibiotics in advance of winter 2023, has left other markets with shortages most noticeably of Clarithromycin and Co-Amoxiclav. Other countries, such as Sweden, has agreed to pay more for essential antibiotics in order to shore up their supply.
For the Irish market, a pro-active response has not yet been forthcoming. There has been little sense of urgency and no measures have yet been taken to future-proof medicine supply for one of the smaller EU markets. Azure has published a Whitepaper discussing in detail some of the local measures that need to be undertaken to underpin supply of critical medicines for Irish patients. Top-line the most crucial are:
Unless and until we have a meaningful response to this problem, it will continue to have negative consequences on patients and pharmacists.
Statement from the Irish Pharmaceutical Healthcare Association (IPHA):
IPHA member companies take the issue of medicines shortages very seriously. When they do occur our member companies give the matter the highest level of attention by national management, seeking to ensure that patients’ care is not interrupted. We are aware that specific, international supply chain issues can lead to delays and shortages and IPHA member companies work closely with the HPRA on these. At European level, the proposed revision of the General Pharmaceutical Legislation includes a number of measures to mitigate shortages. We have made a submission to the cross-departmental Pharmaceutical Strategy Working Group on how shortages can be dealt with going forward across the EU.
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