The use of off-label and unlicensed medicines in Ireland has become increasingly common, particularly in the context of medicine shortages and unmet patient needs. Despite this, Ireland lacks specific regulatory/professional guidance that addresses the relevant issues that pharmacists should consider in the supply of such medicinal products.
The UK Medicines and Healthcare products Regulatory Agency has published detailed guidance on the prescribing and supply of unlicensed medicines. While this guidance may be helpful for pharmacists here, it was developed in a different legal and regulatory system and may not adequately reflect or encompass responsibilities specific to pharmacists practising in Ireland.
This article examines the Irish legal framework governing off-label and unlicensed medicines, the duties of pharmacists when supplying such products and the potential civil, regulatory and professional consequences that may arise.
The Health Products Regulatory Authority (HPRA) is Ireland’s medicines regulator. Its responsibilities include granting marketing authorisations, monitoring medicinal product safety and enforcing medicines legislation.
As a general principle, medicinal products require a valid marketing authorisation before they can be placed on the market in Ireland. Unlicensed products do not have such authorisation, but their sale or supply is permitted, “in response to a bona fide unsolicited order, formulated in accordance with the specifications of a practitioner for use by his individual patients on his direct personal responsibility, in order to fulfil the special needs of those patients.” This is subject to a number of other conditions, most of which are applicable to the manufacturers and wholesalers. Products supplied through this route are generally referred to as exempt medicinal products, or EMPs.
An off-label medicine is not unauthorised, but rather it is an authorised medicinal product being prescribed or used outside the terms of its approved Summary of Product Characteristics (SmPC). Examples include; use for a different indication, use in a different age group, different dosing schedules and alternative routes of administration. Strictly speaking, it may be more accurate to refer to “off-label use of a medicine” than to an “off-label medicine”.
Irish law does not specifically use the terms off-label medicine or off-label use of a medicine. While it does refer to “authorised indication”, “unauthorised indication” and “a therapeutic indication that is not included in the summary of product characteristics under that authorisation”, these are used in very specific instances, apart from which Irish law is largely silent as off-label prescribing and dispensing. However, it is not prohibited and is by implication permitted.
Off-label use and the supply of unauthorised medicinal products arise in a range of circumstances, including medicine shortages, the absence of an authorised product in an appropriate strength or formulation, and the clinical needs of particular patient groups. Although the two situations are often discussed together, they are legally and professionally distinct.
Where a medicine is supplied off-label, the product has already undergone regulatory assessment regarding its quality. However, the regulatory assessment of its safety and efficacy does not necessarily extend to the particular indication, dose, route, patient group or treatment regimen for which it is being used. The pharmacist should therefore avoid treating the existence of a marketing authorisation as regulatory endorsement of the proposed off-label use. The main legal issue for a pharmacist is whether the decision to depart from the authorised indication is clinically and professionally justified.
By contrast, where an EMP is supplied, it has not undergone the Irish or EU marketing-authorisation assessment applicable to an authorised medicinal product placed on the Irish market. The HPRA does not assess individual EMPs for quality, safety or efficacy before they are supplied through the exemption. This does not necessarily mean that the product is unsupported by evidence or has not been assessed elsewhere, but it removes an important element of regulatory assurance available for authorised products. For pharmacists, this increases the importance of robust decision-making and appropriately documenting that decision-making.
The leading Irish authority remains Dunne (an Infant) v National Maternity Hospital. In broad terms, this case provides that negligence is established where the healthcare professional is guilty of a failure that no practitioner of equal status and skill would have committed if acting with ordinary care. Evidence of general and approved professional practice is highly relevant but is not necessarily conclusive where that practice contains an inherent defect that ought to be apparent on due consideration.
There is no case law on the responsibilities of pharmacists when supplying off-label or unlicensed medicines. Coupled with the absence of specific guidance, a pharmacist’s conduct could be assessed by reference to the following:
A pharmacist dispensing an off-label medicine owes the patient the ordinary duty to exercise the care, skill and professional judgment reasonably expected of a competent pharmacist. Off-label status may heighten the need for scrutiny where the indication, dose, route, patient group or treatment duration departs materially from the SmPC.
When dispensing an unlicensed or exempt medicinal product, the pharmacist owes the same underlying duty and must also take reasonable steps, appropriate to the pharmacist’s role and the information available, to satisfy themselves that the product has been sourced through a lawful supply chain and that there is a proper patient-specific basis for its supply as an exempt medicinal product. The availability of an authorised alternative is an important consideration but should not be treated as automatically decisive. An authorised product may be unsuitable for the individual patient because of its formulation, strength, route of administration, excipients, availability or other clinical considerations. Conversely, supplying an EMP without identifying any patient-specific reason why an authorised product would not meet the patient’s needs may call into question both the applicability of the statutory exemption and the professional justification for the supply. It is therefore important that the pharmacist has sufficient information to understand why the prescriber considers an EMP necessary and to carry out the pharmacist’s own review of the pharmaceutical and therapeutic appropriateness of the proposed therapy. For example, a pharmacist may have a better understanding of what medicines are or are not in short supply and therefore whether licensed alternatives may be available.
Depending on the circumstances, negligence could consist of failing to recognise and query an unusual or apparently unsafe regimen, failing to contact the prescriber where clarification was reasonably required, dispensing despite an unresolved material safety concern, or failing to give appropriate warnings or instructions, provided that the breach caused injury.
The legal and regulatory risks associated with the supply of off-label and exempt medicinal products extend beyond the possibility of a negligence claim. Pharmacists could of course be the subject of a fitness to practise complaint, even in the absence of a negligence claim.
The PSI Code of Conduct states that pharmacists must place patient welfare first and act in accordance with legislation. In the context of off-label and unlicensed medicines, it is important to be able to demonstrate a well-reasoned and documented decision-making process, including for example as regards Regulation 9 of the Regulation of Retail Pharmacy Businesses Regulations 2008. This requires a pharmacist to review the prescription having regard to the pharmaceutical and therapeutic appropriateness of the therapy and to screen for reasonably identifiable problems, including incorrect dosage or duration, interactions, duplication and allergies. The pharmacist must also provide sufficient information and advice for proper use — again, this should be properly documented. It is important to bear in mind that complaints are often made months or years after the event and contemporaneous records may provide strong evidence of the pharmacist’s decision making in the event of a complaint, inspection or indeed a negligence claim.
Off-label use and the supply of exempt medicinal products may be clinically justified and in appropriate circumstances necessary to meet an individual patient’s needs. However, neither the existence of a prescription nor the prescriber’s clinical responsibility removes the pharmacist’s independent obligations concerning pharmaceutical and therapeutic appropriateness, patient counselling and safe supply.
With the increasing use of off-label and exempt medicinal products in Ireland and the ongoing medicine shortages, the need for practical Irish guidance in this area remains vital. Until specific Irish professional guidance is developed, pharmacists should apply a structured and proportionate decision-making process, seek clarification from the prescriber where a material issue arises, give the patient appropriate information, and make contemporaneous records of significant decisions and communications.
While a clear, structured and well-documented approach will not remove risk entirely, it will allow pharmacists to demonstrate compliance with their regulatory obligations and the professional standards expected of them.
References available on request.
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