Oireachtas Joint and Select Committees
Wednesday, 19 September 2018
Joint Oireachtas Committee on Health
Licensing of Abortion Medication: Health Products Regulatory Authority
We are now meeting representatives from the Health Products Regulatory Authority to discuss abortion medication as envisaged in the termination of pregnancy legislation. On behalf of the committee, I welcome Mr. John Lynch and Dr. Elaine Breslin from the authority. I apologise to them for keeping them so long. Our previous session overran.
I draw the attention of witnesses to the fact that by virtue of section 17(2)(l) of the Defamation Act 2009, they are protected by absolute privilege in respect of their evidence to the joint committee. However, if they are directed by the committee to cease giving evidence on a particular matter and they continue to do so, they are entitled thereafter only to qualified privilege in respect of their evidence. They are directed that only evidence connected with the subject matter of these proceedings is to be given. They are asked to respect the parliamentary practice to the effect that, where possible, they should not criticise or make charges against any person, persons or entity by name or in such a way as to make him, her or it identifiable.
Members are reminded of the long-standing parliamentary practice to the effect that they should not comment on, criticise or make charges against a person outside the Houses or an official by name or in such a way as to make him or her identifiable.
I advise the witnesses that any opening statements they make will be published on the committee's website after the meeting. I invite Dr. Elaine Breslin to make her opening statement.
Dr. Elaine Breslin:
I thank the Chairman and the committee members. I am a clinical assessment manager, and I am joined by my colleague, John Lynch, the director of compliance. We are pleased to provide this opening statement in response to the committee’s request to consider the matter of the authorisation of medicines for the termination of pregnancy, in light of the impending introduction of abortion services in Ireland. The HPRA, as the competent authority for the authorisation of health products in Ireland, seeks to fully inform the committee in this regard by providing the following information.
We will briefly outline the medicines for medical termination of pregnancy and the system for the authorisation of medicines in Ireland and across the European network, in particular the mutual recognition procedure which is relevant to these medicines. We will then provide an update on our work to date to secure authorised medicines, while respecting the applicants’ confidentiality. We will conclude with a description of the exempt medicines scheme, which is relevant to facilitating the availability of a medicine where an authorised equivalent is not available.
By way of background, medical termination of pregnancy is achieved by the taking of two medicines, up to 48 hours apart, to induce a miscarriage. The use of these medicines, in combination, results in a safer and more effective procedure. In the European Union, both of these medicines are subject to prescription and can only be prescribed and administered in accordance with a country’s national laws and regulations.
Dr. Elaine Breslin:
The first medicine, mifepristone, acts by blocking the effects of progesterone, a hormone which is needed for pregnancy to continue. It can also be used to soften and open the entrance or the cervix to the womb or uterus. The second medicine, misoprostol, a prostaglandin, causes contraction of the womb and also softens the cervix. Gemeprost, an alternative prostaglandin, may be used instead of misoprostol.
At present in Ireland, there are no medicines authorised for the termination of pregnancy. Medicines for this medical indication are authorised in many European Union member states. It should be noted that, across the EU, only a small number of companies are involved in the supply of these medicines.
Apart from exceptional circumstances, to which I will refer later, under European and Irish law, medicines must be authorised before being marketed in a member state. This is to ensure they meet the required standards, and patients have access to information on the safe and appropriate use of medicines.
A medicine is authorised by the Health Products Regulatory Authority, HPRA, for sale and supply to the Irish market, following a detailed technical assessment of an application for a marketing authorisation. This application is submitted by a company seeking to market a medicine in Ireland, in the form of a dossier which contains data to support the medicine’s quality, safety and efficacy. If, following assessment, the benefit-risk of the medicine is positive, a marketing authorisation is granted. The company is then termed the marketing authorisation holder.
Medicines used in the termination of pregnancy are currently authorised in other European member states under a scheme of mutual recognition. Under this scheme, a single EU member state is designated as the reference member state. The reference member state is the EU-based competent authority which was responsible for assessment of the original application dossier and the ongoing co-ordination of dossier updates on behalf of other named EU countries, known as concerned member states.
EU law requires that where a medicine is authorised in another member state, a mutual recognition procedure must be used. Therefore, in order to market a medicine in Ireland for this indication, a marketing authorisation holder must apply to the reference member state to extend the authorisation to the Irish market and, simultaneously, submit an application dossier to the HPRA to
allow the national phase of this process to occur. This procedure is required to be completed within a maximum of 90 days of the HPRA’s validation of the company’s application dossier. The HPRA will grant an authorisation, having confirmed the medicine’s benefit-to-risk balance based on an abridged review, which acknowledges the authorisation granted by the reference member state.
Following the outcome of the referendum relating to the eighth amendment of the Constitution in May 2018, the HPRA sought to identify medicines actively marketed in other EU member states, which were indicated for use in the medical termination of pregnancy, and to inquire of the marketing authorisation holders as to their plans to apply for authorisation to market their medicines in Ireland. This was with a view to, if possible, ensuring authorised medicines would be available at the time of coming into force of the legislation on medical termination of pregnancy.
While the HPRA cannot comment on specific applications for reasons of confidentiality, we can confirm that, to date, we have received applications and these are currently being assessed under 90-day mutual recognition procedures. If the applications are considered acceptable, marketing authorisations can be issued in late 2018.
It should be noted that these applications are running in a common procedure with a number of other EU concerned member states, so while we do not foresee significant issues, we would insert this note of caution with respect to the impact of other member states’ assessment on the timing of any final authorisation in Ireland.
If an authorisation is granted for a medicine for the termination of pregnancy, the HPRA has requested that the company would expedite the process for making supplies available in Ireland to facilitate the timely implementation of services.
In the event that medicines for the medical termination of pregnancy are not authorised by the end of 2018, there is an exemption in law for the treatment of patients with medical conditions for which an authorised medicine is not available. This is known as the exempt medicines scheme. Specifically, an unauthorised medicine is considered exempt from authorisation when it is supplied
under prescription from a registered doctor for treatment of individual patients in order to fulfil an unmet medical need.
The HPRA does not issue approvals for use of exempt medicines. Wholesalers and manufacturers based in Ireland are required to notify the HPRA when they have sourced exempt medicines for the purposes of supply in Ireland. The wholesaler or manufacturer is required to have processes in place to capture and record any adverse reaction notified in respect of an exempt medicine and to report this to the HPRA.
Over the coming weeks, the HPRA will assess the applications received to date and maintain contact with prospective marketing authorisation holders regarding the supply of their medicines in Ireland. The HPRA anticipates receipt of further applications in early 2019, and these will also be made through the mutual recognition procedure.
The HPRA is aware of the importance of ensuring supply of medicines for the medical termination of pregnancy. We will continue to work with the Department of Health, relevant stakeholders and companies to put in place the services mandated by the forthcoming legislation. We will be happy to address any questions.
I thank Dr. Breslin. In the absence of the Chairman, I have the list of speakers and as my name is at the top, I will ask my questions first if members agree.
Much has been made of the preparations for the legislation. While it has not yet been published, we have an idea of what it will contain. I am relieved to note that it appears a good degree of work has already been done by the HPRA.
The previous witnesses spoke of the need to bring everybody together to ensure they were all sitting around the same table.
I will ask the witnesses the same questions that were asked of those groups. Has the HPRA been involved with the Department of Health and in these meetings? Is there an understanding across the board on how prepared or otherwise Ireland is for the implementation of the legislation?
My second question relates to safety. For anybody who cares to look, I presume that there is evidence with regard to the safety of the proposed drugs and that is not proposed to use anything new or different. Is it proposed to use drugs used in other jurisdictions that have a good safety record and so on?
Dr. Elaine Breslin:
I reassure the Vice Chairman that we have been in constant contact with the Department since the referendum in May 2018. We have had numerous meetings and teleconferences. We have also been in constant contact with the HSE regarding the supply of medicines. Our most recent meeting with both groups was on Monday. It is our practice to work closely with the Department on the supply of medicines and in preparing for the supply of new medicines.
On the Vice Chairman's second question, one of the aspects we review routinely is the safety of medicines prior to their being placed on the Irish market. As she correctly said, the medicines used in the termination of pregnancy in other EU countries are long authorised and their safety is well established. It is known, for example, that the common side effects associated with these medicines are symptoms such as cramping, pain, bleeding, nausea and vomiting. Women can be allergic to these medicines and certain contraindications need to be taken account of.
With regard to the process I have described around the authorisation of medicines, the company submits a dossier to us but we then receive an independent report from the reference member state that has authorised this medicine and that has experience of the safe and effective use of that medicine. We receive that independent assessment, which is part of our review along with the dossier from the company. We can give comments back on that and the company has an opportunity to respond. The procedure must be concluded within 90 days. We have sought to conclude these procedures earlier if at all possible.
In the opening statement, reference was made to the second tablet that contains either Misoprostol or Gemeprost. Is either more effective? Is the Misoprostol the first line and if there is none available, is Gemeprost an equivalent? I am just trying to establish that we get the optimum product.
Dr. Breslin referred to more than one company. While I understand the commercial sensitivity, has more than one company applied for a heath technology assessment on the product? I want to get to the issue of price. If only one company is coming in and if we are under pressure to deliver, there is an argument to be made that the company can, perhaps, name its price. Will the Dr. Breslin elaborate on whether there is only one player in the market? I cannot imagine this would make a company a huge amount.
What are the conditions of use of medicines and the licensing? I understand that in other jurisdictions the two termination of pregnancy pills are licensed for up to ten weeks of pregnancy. Are there special conditions such as dating scans, ectopic situations or other contraindications? Will Dr. Breslin elaborate on other issues that might come down the road?
With regard to the unlicensed medicines scheme, and I am speaking hypothetically, if a product was not available and everything else was available in January, and if it had to be supplied under the exempt medicines scheme by a doctor, if there is a 0.1% chance of something going wrong in that period, where would the liability fall? Would it be the personal liability of the doctor? With many exempt medicines, the liability falls to the practitioner or the prescriber and sometimes the pharmacist.
Dr. Elaine Breslin:
I thank the Deputy for that question. I shall address the clinical issues. The usual schedule is that the Mifepristone is taken first. This would be early termination of pregnancy. Depending on the dose, it is one tablet. It is usual that Misoprostol is taken second, which is advised by the Royal College of Obstetricians and Gynaecologists, within 48 hours. The Deputy is probably aware that there are different regimens. Those two products are attractive or useful in the community setting because they are indicative for oral use. Gemeprost is for vaginal use and is perhaps a less useful product. If the intention of the system is for this to operate within the community and for women to take the first medicine under the supervision of the medical practitioner and the second medicine at home, it would be more practical that it be an oral medicine. That is usually the system. We are aware that Gemeprost is used but according to the information we have to date, it is mainly for hospital-based use, and it may be used for the more complex types of terminations, as were discussed at the earlier session.
The Deputy asked if there was more than one player in the market. Three companies supply these medicines throughout the EU and we actively engaging with them. As I clarified earlier, we must initiate a mutual recognition procedure or be involved in that kind of procedure. We have engaged with each of these companies requesting them to make applications. We have also engaged with member states that have authorised those medicines asking them to act as the reference member state. We are approaching this from two aspects with a view to maximising the opportunity of getting applications here.
The pricing is outside the remit of the HPRA. We have nothing to do with that. As I said earlier, we have had close contact with primary care reimbursement service and with the Department, and we have mentioned to them the fact that there are three companies marketing these. There are a limited number of options available but these companies are marketing throughout the EU.
On the conditions of use, the product information requires that pregnancy is diagnosed using biological methods such as a urine or blood test to measure HCG or an ultrasound. The conditions of use do not mandate how a pregnancy is diagnosed, just that pregnancy must be diagnosed prior to the administration of the first medicine. There are exclusion criteria. For example, if there was concern about an ectopic pregnancy when the woman presents with pain or bleeding or with a past medical history, it would be taken into account. If a women has an inter-uterine device, which is a contraceptive device, this is also a contraindication to the use of these medicines. All of this is part of the routine review. The rhesus factor is also assessed. The product information will contain the basic information about the indications, the contraindications to use, the side effects of the treatment and how to use the medicine safely.
Since the Protection of Life During Pregnancy Act 2013, these medicines for the termination of pregnancy have been imported through the exempt scheme for supply to hospitals only. Under the Act, they are permitted for medical terminations of pregnancy in certain circumstances but it has to be a hospital-based treatment. There is an established exempt supply scheme for the companies that manufacture these medicines and that will be helpful moving forward.
Liability is not a matter for us. We permit the exempt scheme and I will ask my colleague, Mr. Lynch, to give more details on that, but essentially the law states that there must be a medical prescription by a medical practitioner who is registered in Ireland and it must be for a patient under his or her care.
Mr. John Lynch:
It is correct that within the European medicines directive, which has been transposed, that the use of exempt or unauthorised products must be to meet the special needs of patients under the direct responsibility of a medical practitioner. The scheme has been in operation since 2008 and it is a recognition that we are a small market. There can be occasions where the authorised product is not available or it is simply a niche product and it is not commercially viable for a company to put in an application for a marketing authorisation.
Authorised wholesalers whom we inspect and authorise can source exempt products generally when the products are authorised in other member states and then can bring them into the country. They notify the Health Products Regulatory Authority of the receipt of those products and then they can supply hospitals, pharmacies or practitioners, specifically for patients under their care. The value of that is while a product is not authorised in our market, in the event that we get a notification from other member states for a recall of that product, we can at least check our database of notified exempt products and initiate a recall through the wholesaler who has sourced the product.
We heard earlier that one could be looking at 10,000 procedures a year and then if 70% happen before ten weeks, one is looking at potentially 7,000 doses of product. Would that be considered a niche market? I am concerned about the small population size and price and being caught in January having to pay. Is ten or 100 people niche?
Mr. John Lynch:
In our experience it varies. Some of them are old products. The Deputy might be familiar with Amitriptyline, which has a specific usage nowadays, but there is no authorised version of it or Bendroflumethiazide, again not an authorised version, but older products.
As Dr. Breslin stated, we cannot speak on behalf of the companies, and what is commercially viable for one company may not be for another. On the other extreme, there are some new expensive medicines for specific conditions but it is commercially viable for a company to make an application through the European system for a central authorisation for those products. It depends on what a company sees as a commercial proposition.
We are seeking to ensure there is supply available for the initiation of these services.
I thank the witnesses. We have no further questions, which is in part down to the comprehensive nature of the submission made in advance, which helped to clear the issues up for members.
I thank Mr. John Lynch and Dr. Elaine Breslin for appearing and for sharing information with us. We have a long road to travel but we are making good progress.