I am saddened by the evidence presented by Ms Sloan, whom I have not met previously. I offer my sympathy to her and her family on their avoidable tragedy. We have prepared an introductory statement based on the committee's request to us to appear before it. I would also be happy to respond to any questions or additional comments. Many of the issues raised are unfortunately outside of the capacity of the Irish Medicines Board, IMB, to address because they pertain to policies of the Department of Health and other agencies. I am joined by my colleagues, Ms Lorraine Nolan, director of human products authorisation and registration, and Mr. John Lynch, director of compliance.
The IMB, which is shortly to be renamed as the Healthcare Products Regulatory Authority, HPRA, is the competent authority in Ireland for health product regulation. The mission of the IMB is to protect and enhance public and animal health through the regulation of medicines, medical devices and other health products. In the context of human medicines, one of the IMB’s key areas of responsibility includes the approval of medicines prior to their being placed on the market. Before a new medicine can be placed on the Irish market, it must be assessed and authorised by the IMB or by the European Medicines Agency. The assessment involves establishing that a medicine’s public health benefits outweigh its known risks based on an evaluation of the scientific data on the quality, safety and efficacy of the product. Where the benefit to risk ratio is considered positive, the product may be granted a marketing authorisation.
Adrenaline is a hormone which occurs naturally in the body but is also available as a medicine indicated in the emergency treatment of severe acute allergic reactions, or anaphylaxis. A number of medicines containing adrenaline are authorised for use in Ireland. Adrenaline products can be administered intravenously, IV, intramuscularly, IM, or subcutaneously, SC. IV administration must be performed by a health care professional.
Adrenaline auto-injectors, AAIs, consist of an adrenaline solution in a pre-filled delivery system designed for self-administration by the IM route. AAIs are used for the treatment of anaphylaxis, which is a severe and life threatening systemic allergic reaction. Such an allergic reaction can be rapid in onset, very severe in nature and can affect persons of all ages. Adrenaline administered by the IM route acts more quickly than when given by SC injection. This is an important consideration because rapid action of adrenaline is critical in reversing the symptoms of anaphylaxis. The exact incidence of anaphylaxis is not known but it is estimated that under 2% of the population per year experience anaphylaxis. Anaphylaxis can occur if someone who is allergic to a particular trigger, such as a food, insect bites and stings or a medicine, comes in contact with that trigger. Contact with the trigger results in substances such as histamine being released from certain blood cells in the body, thereby causing a clinical reaction which may involve many organs in the body, including the respiratory system, heart and kidneys.
In Ireland, three different AAI product ranges are currently authorised, namely, Anapen, Epipen and Jext. Each product range includes two different strengths, for adult and paediatric treatment, respectively. These products are all authorised under European procedures, which result in authorisations in many EU member states.
Anapen and Anapen Junior were the first auto-injector products to be authorised for the Irish market in 2003. In the past three years the range of adrenaline products available has been extended through the introduction of the two new ranges. Jext was authorised in 2011 and placed on to the Irish market in 2013. Epipen and Epipen Junior product was originally authorised in Ireland until mid-2010, at which time the authorisation was withdrawn by the then marketing authorisation holder for commercial reasons. In 2012, the product was relaunched in Ireland via an application through the European procedure and it finally came to market in 2014.
Adrenaline auto-injectors are automatic injectors that have been designed and developed for use by lay people for immediate self-treatment of anaphylaxis in an emergency situation, prior to seeking further appropriate medical treatment.
The difference and advantage of the adrenaline auto-injector products versus other adrenaline products, such as other pre-filled syringe systems or standard injectable forms, is that the intervention of a health care professional is not required for administration of the product.
Given the nature of the auto-injector, the product information and patient information leaflets contain detailed instructions on how to use the product. These include both written and pictorial descriptions for an emergency situation covering how to prepare the product for use and how to administer the product. They also highlight the need to seek immediate medical assistance.
In the 11 years since Anapen has been authorised there have been a number of updates to the product to improve its design and functionality. These include the incorporation of a variety of safety features to ensure safe administration of the product including accuracy of dosing, avoidance of needle stick injuries and inadvertent firing of the device. Another important update that was made related to the required storage conditions, which means that the product can now be stored at room temperature rather than in a refrigerator as originally required. This allows patients with allergies to carry the product with them at all times. While there are some variations in design between the available auto-injectors, the Jext and EpiPen ranges have similar design characteristics.
AAIs are supplied in packs containing two auto-injectors. One reason for this is the risk of biphasic anaphylaxis which can affect approximately 20% of patients who suffer an allergic reaction. Biphasic anaphylaxis is defined as the recurrence of symptoms in a patient without continued exposure to the allergen. The approved product information states that, in the absence of clinical improvement or if deterioration occurs, a second injection may be administered within a defined timeframe - ranging from five to 15 minutes - after the first injection. Therefore, it is important for patients to carry two AAIs in case a second injection is needed.
Notwithstanding the above developments in these products, AAIs are complex systems due both to the characteristics of the adrenaline active substance and of the delivery device, which is designed to be as patient-friendly as possible. The manufacture of these products is also complex.
I will now comment briefly on the current prescription status. Under the EU Medicines Directive and Irish law, products for injection must be supplied on prescription only. Accordingly, the marketing authorisations for these products stipulate that they are prescription only.
In addition to this legal requirement, there are safety concerns in relation to the possible incorrect use of adrenaline. These include the misdiagnosis of anaphylaxis and the potential adverse implications of incorrect or inappropriate administration of adrenaline, such as administration to patients with a history of - or underlying - cardiac arrhythmias, cardiovascular disease including angina and hypertension, where incorrect administration could result in an exacerbation of these conditions or significantly worsen health care outcomes. The fact that these are prescription medicines - and will be because that is what is required - does not mean that they cannot be provided in the kind of settings as described by earlier contributors.
I will now mention ongoing regulatory procedures. With the Chairman's agreement, that particular commentary is not especially relevant to the discussion, nor is the latter part of my presentation concerning shelf-life. Suffice it to say that shelf-life is an important issue, which feeds into any decisions that might be made about future availability.
I do have a brief comment on shelf-life. Adrenaline is a relatively unstable substance which readily degrades. This degradation is due to the chemical nature of the substance and is accelerated by factors such as exposure to light and oxygen, and pH changes. The manufacturers of all the authorised products have taken a number of steps to minimise the degradation of adrenaline and prolong the shelf-life, including protection from light and oxygen, the inclusion of an antioxidant in the formulations, and control of the pH.
While there are some minor variations in the shelf-life of the authorised products, the shelf-life of AAIs ranges from 18 months to two years. It is important that these products are not used after the shelf-life has expired. After this time the efficacy of the product can be reduced which may result in the product not working as required in an emergency situation.
If the Chairman agrees, I can stop there.
