The Pharma Legal Handbook: Ireland
Join industry executives in staying informed on pharma regulations in Ireland.
Regulation, Pricing, Clinical Trials, Marketing, Manufacturing, Trademarks, Patents, and more!
Get your pharmaceutical legal and regulatory questions answered in The Pharma Legal Handbook – a must-have guide for any company operating in the country or looking to enter the market.
Prepared in association with Mason Hayes & Curran, a leading international law firm.
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Last Update February 2020
1. Regulatory Reform: Ireland
1. Are there proposals for reform or significant change to the healthcare system?
In 2020, the onset of the Covid-19 global pandemic wreaked havoc on healthcare systems worldwide. Ireland, like many other countries had to adapt quickly and provide safeguards and protections within the Irish healthcare system in an effort to combat the spread of Covid-19. As a result, there was an immediate need for the use of digital health technologies such as the HSE Covid-19 track and trace mobile phone app, which has since been further developed to allow users to store their vaccination certificates. The EC recently proposed the ‘EU4Health’ programme as part of a Covid-19 recovery response programme, and it aims to raise €5.1 billion for the digital transformation of the EU health sector and ensure preparedness for future cross border health threats.
In line with the EC’s efforts, the Irish Government’s ‘Programme for Government’ published in October 2020 seeks to expand and build on the regular use of digital health technologies within the healthcare service. Examples include electronic prescribing (ePrescribing) whereby patients can order repeat prescriptions online, online patient scheduling and referral systems as well as include newer technologies such as ambient assistive living (AAL) systems, robotic surgical systems and body-worn sensor devices. The Government also hopes to build on the progress made in responding to Covid-19 by working with healthcare professionals to improve eHealth measures and providing for the secure electronic sharing of patient information, lab results, diagnostic imaging reports, and prescription orders between medical providers.
The MDR came into effect on 26 May 2021, bringing about significant changes in the medical devices sphere and the 2021 Regulations confer on the HPRA various regulatory functions provided for under the MDR such as classification, market surveillance, clinical investigations and enforcement. As elaborated upon in Question 2, the new IVDR will bring a host of changes for the regulation of the safety and marketing of IVDs placed on the EU market. The IVDR entered into force on 25 May 2017 and will take full effect, after a five-year transition period on 26 May 2022. Owing to concerns over market disruptions expected to be caused by a lack of appropriately designated notified bodies, the European Commission has recently proposed an extension of the 2-year transition phase currently provided for under the IVDR. Under this proposal, the highest risk devices (Class D) would have until May 2025 to undergo conformity assessment by a notified body. Moderate-risk devices (Class C) would have until May 2026 and lower risk Class B and Class A sterile devices would have until May 2027. Lastly, per Question 16, implementation of the new Clinical Trial Regulation (EU) 536/2014 is planned to take place in 2022.
The decision by the United Kingdom in 2016 to leave the European Union (Brexit) has had and will continue to have long lasting effects. As a result of Brexit, the UK is effectively a third country which, given the geographical location, has created potential for supply chain issues for Ireland. Furthermore, the EU and UK have long shared information in the medical and healthcare spheres in a conscious effort to ensure consumer safety. However due to Brexit, the UK will not exist in the EUDAMED database and nor will the UK’s Medicines and Healthcare products Regulatory Agency (the MHRA) be part of EU’s competent authorities, bringing about a loss of valuable health data for the EU and UK alike.
2. When are they likely to come into force?
The advancement and use of digital health technologies has already begun in Ireland and will be an ongoing feature in the provision of healthcare services. This sector will continuously innovate, develop, and implement technologies, and thus reforms and advancements in healthcare will likely be a consistent feature of the Irish healthcare system.
The MDR came into effect on 26 May 2021. Although directly applicable, the MDR has also been supplemented by Irish implementing legislation such as the 2021 Regulations which also came into force on 26 May 2021. The IVDR (as discussed in Question 2), entered into force on 25 May 2017 and will take full effect, after a five-year transition period on 26 May 2022. Owing to concerns over market disruptions expected to be caused by a lack of appropriately designated notified bodies, the European Commission has recently proposed an extension of the 2-year transition phase currently provided for under the IVDR. Under this proposal, the highest risk devices (Class D) would have until May 2025 to undergo conformity assessment by a notified body. Moderate-risk devices (Class C) would have until May 2026 and lower risk Class B and Class A sterile devices would have until May 2027. As outlined in Question 16 and 66 above, the new Clinical Trial Regulation (EU) 536/2014 was adopted on 16 April 2014, and implementation is planned to take place in 2022.
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2. Patents & Trademarks: Ireland
1. What are the basic requirements to obtain patent and trademark protection?
The requirements to obtain patent protection are outlined on the website of the Intellectual Property Office of Ireland (IPOI). Any person can make an application for a patent, and the right to the patent belongs to the inventor or their successor in title. Applications can be filed jointly and by a patent agent on behalf of an applicant. The basic application requirements consist of the following:
- A request for the grant of a patent. (Completing the application Form No.1, which is an online form)
- A specification containing a description of the invention, one or more claims defining the matter for which protection is sought and any drawings needed for the disclosure.
- An abstract containing a summary of the matter contained in the specification.
- The prescribed filing fee.
The IPOI also deals with trademark protection and in order to obtain such protection, an applicant completes the requisite form and will ordinarily wait at least three months before registering their trademark. The three-month period allows for any potential oppositions to the application to be filed. At the end of this three-month period, if there is no opposition filed, the application will proceed to registration. When a trademark is registered, a registration certificate will issue to the proprietor and the registration will last for 10 years, at which point it can be renewed for a further 10-year period.
2. What agencies or bodies regulate patents and trademarks?
The IPOI is the official government body responsible for intellectual property rights including patents and trademarks.
3. What products, substances, and processes can be protected by patents or trademarks and what types cannot be protected?
Section 9(1) of the Patents Act 1992 states that, an invention in all fields of technology shall be patentable if it is susceptible of industrial application, is new and involves an inventive step.
The 1992 Act as amended explicitly states that the following are not patentable:
- An aesthetic creation;
- A discovery, scientific theory or a mathematical method;
- A scheme, rule or method of performing a mental act, playing a game or doing business, or a program for a computer;
- The presentation of information;
- A method for treatment of the human or animal body (this exclusion does not apply to a product for use in any such method);
- A plant or animal variety or an essentially biological process for the production of plants or animals other than a microbiological process for the products thereof; and/or
- An invention whose commercial exploitation would be contrary to public order or morality.
Under Irish law, a trademark is any sign which is capable of distinguishing goods or services of one undertaking from those of other undertakings. The legislation provides a non-exhaustive list of examples such as words, designs, letters, numerals, colours, or the shape of goods or their packaging, or sounds.
Therefore, in order to be eligible for registration, the trademark must be a sign, must be capable of being represented on the register in a manner which enables the competent authorities and the public to determine the clear and precise subject matter of the protection afforded to its proprietor and it must be capable of distinguishing goods or services of one undertaking from those of other undertakings.
Furthermore, section 8 of the Trade Marks Act 1996 (as amended) provides certain additional absolute grounds for refusal of a trade mark application. For example, trademarks which are devoid of distinctive character, trademarks which are descriptive, those which are contrary to public policy or accepted principles of morality, and those applied for in bad faith will not proceed to registration.
4. How can patents and trademarks be revoked?
Section 58 of the Patents Act 1992 as amended outlines the grounds for seeking revocation of a patent. A revocation application can be brought either before the High Court or the Controller and, generally, there is no requirement that the party seeking revocation be an interested party.
The grounds for revocation of a patent under the 1992 Act as amended are:
- The subject matter of the patent is not patentable under the 1992 Act;
- The specification of the patent does not disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art;
- An amendment to a specification added new matter;
- An amendment extends the protection conferred by the patent, which in effect broadens the scope of the claims of the granted patent which should not have been allowed; and/or
- The proprietor of the patent is not entitled.
An application for revocation of a trademark can be brought before the High Court or the Controller and by any person.
Non-use of a trademark can lead to the revocation of that trademark but, contrary to some other jurisdictions wherein the proprietor must demonstrate use upon renewal, in Ireland non-use can only lead to revocation where an action is brought by a third party. Section 51(1) of the Trade Marks Act 1996 outlines that a trademark can be revoked for non-use where:
- The mark has not been put to genuine use in the State in relation to the goods/services specified in the registration within five years from when the trademark was registered; or
- Where after registration, genuine use in relation to the goods/services is suspended for an uninterrupted period of five years.
An exception exists in both instances where there are proper reasons for non-use. Proper reasons refer to circumstances unconnected to the trade mark proprietor. For example, a proper reason would be the requirement to seek regulatory approval before placing a medical device or pharmaceutical product on the market.
The Trade Marks Act 1996 shifted the burden of establishing use on to the trademark proprietor. Section 51(1)(c) of the 1996 Act further provides that a trademark can be revoked where a trademark has become the common name in the trade for a product or service as a consequence of the acts or inactivity of the proprietor. It is therefore important for a proprietor to police its trademark.
Section 51(1)(d) of the 1996 Act outlines that revocation can also occur due to use which is liable to mislead the public, for example, in a manner which is misleading as to the nature, quality, or geographical origin of the goods or services.
Moreover, if you are of the opinion that a trade mark should not have been registered, and if you have missed the opportunity to oppose it, it is possible to seek to invalidate the registration pursuant to Section 52 of the 1996 Act. The onus in establishing invalidity rests on the person seeking such declaration of invalidity. An invalidity action can only be taken against a trade mark registration and it is therefore not relevant to a trade mark at the application stage.
5. Are foreign patents and trademarks recognized and, if so, under what circumstances?
The Patent Co-operation Treaty (PCT) established in 1970 and administered by the World Intellectual Property Organisation (WIPO) allows applicants to obtain patent protection in a large number of countries around the world. Under this Treaty, foreign patents will be recognised in Ireland. A PCT application requesting patent protection in Ireland is categorised as an application for a European patent for Ireland and will be processed by the European Patents Office in accordance with the European Patent Convention (EPC).
The European Union Intellectual Property Office (EUIPO) has an online fast track system allowing a single application to be made (at a cost of €850) to provide trademark protection throughout the EU. This registration is valid in all EU Member States for a period of 10 years and can be renewed indefinitely every 10 years. Through this mechanism, EU trademarks can be recognised in Ireland.
Furthermore, Ireland is a signatory to the Madrid Protocol, under which, an application can be submitted to the WIPO. This international system of registration gives a trademark owner the option to apply to protect their trademark in several countries worldwide by filing one application, in one language, with one set of fees in one currency (Swiss francs). The Madrid Protocol requires that an international application must be based on a national trademark application, for example, one which has been filed in the IPOI, which is then known as the ‘Office of Origin’. International applications will only be accepted at the IPOI where Ireland is the Country of Origin. The crucial point under this system of recognition of foreign trademarks is that, applications received where Ireland is not the correct Country of Origin will not be accepted.
6. Are there any non-patent/trademark barriers to competition to protect medicines or devices?
Applicants are not required to provide the results of pre-clinical and clinical trials if they can show the product is a generic medicinal product, or a similar biological product to a product authorised in another MS or the EU for at least eight years (or six years, if the application for the reference product was submitted prior to 30 October 2005). However, the transitional data protection principles require that the generic or similar biological product, once authorised, cannot be placed on the market for 10 or 11 years (depending on the exclusivity period) following authorisation of the reference product. Under the 2007 Medicinal Products (Control of Placing on the Market) Regulations, if the application for the reference product was made before 30 October 2005, the period is reduced to six years. Under the EU Regulations on Orphan Medicinal Products, the owner of an orphan product is entitled to ten years’ market exclusivity if certain conditions are met.
7. Are there restrictions on the types of medicines or devices that can be granted patent and trademark protection?
No. The Patents Act 1992 does not include a special provision in respect of patents relating to food, medicine or to medical, surgical or other remedial devices. Moreover, second medical uses of known medicaments are now patentable under section 11(4) of the 1992 Act (as amended).
In relation to trade marks, so long as the mark in question is a sign which is capable of distinguishing goods or services of one undertaking from those of other undertakings it will be capable of trademark protection. Similarly, the absolute and relative grounds for refusal as set out in sections 8 and 10 of the Trade Marks Act 1996 must be overcome. The absolute grounds for refusal include the following:
- Signs which do not fall within the definition of a trade mark;
- Trade Marks which are devoid of distinctive character;
- Descriptive trade marks;
- Trade Marks which consist exclusively of signs or indications which have become customary in the current language or in the bona fide and established practices of the trade;
- Signs which consist exclusively of the shape or another characteristic which results from the nature of the goods themselves, the shape or another characteristic of goods which is necessary to obtain a technical result, or the shape or another characteristic which gives substantial value to the goods;
- Trade Marks contrary to public policy or to accepted principles of morality;
- •eceptive trade marks;
- Trade Marks, the use of which is prohibited by law including EU legislation for the protection of designations of origin, traditional terms for wine, traditional specialties guaranteed or plant variety rights; or”
- Trade Marks applied for in bad faith.
8. Must a patent or trademark license agreement with a foreign licensor be approved or accepted by any government or regulatory body?
Whilst the license agreement does not have to be approved or accepted by a government or regulatory body it should generally be registered with the office which the trade mark or patent is registered with (for example, the IPOI, the EUIPO etc). Registration is compulsory in some jurisdictions and not in others. In Ireland registration is not compulsory but not having a license agreement registered may restrict what a licensor can do or be entitled to do. Registration requirements do not vary in circumstances where a licensor is foreign. One possible exception would arise where there are competition law reasons why a licence should not take place. In those circumstances, the CCPC may investigate the circumstances surrounding the licence and the impact on the relevant market for anti-competitive behaviour.
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3. Product Liability: Ireland
1. What types of liability are recognized in your jurisdiction?
There are four main sources of product liability in Ireland:
The Liability for Defective Products Act 1991 transposed the EU Product Liability Directive 85/374/EC and is the primary source of product liability legislation in Ireland. It adds to the traditional theories of product liability available in tort and contract. It provides for strict liability where damage is caused either wholly or partly by the defect in a product.
The tort of negligence can also apply to claims for defective products. The relevant test is to establish whether the defendant (e.g. manufacturer, the supplier or importer) owed a duty of care to the plaintiff, whether they breached this duty and the breach caused the alleged damage.
Sales of goods are regulated by the Sale of Goods Act 1893 and the Sale of Goods and Supply of Services Act 1980. The legislation implies a contractual obligation on the seller to ensure that the products they are selling are of merchantable quality. They will be deemed to have breached this implied term if their products are not fit for the purpose or purposes for which goods of that kind are commonly purchased, if they are not as durable as is reasonable to expect having regard to their description, their price and all other relevant circumstances, and if a product can foreseeably be considered to breach the implied term that it correspond with its description. The EC (Certain Aspects of the Sale of Consumer Goods and Associated Guarantees) Regulations 2003 also apply and require that goods delivered under a contract of sale must be in conformity with that contract.
The EC (General Product Safety) Regulations 2004 (GPSR) implemented EC Directive 2001/95, and under this piece of legislation it is an offence for a producer to place an ‘unsafe’ product on the market. ‘Producer’ is defined as being either:
- A manufacturer of the product;
- A manufacturer’s representative in the EU (if the manufacturer is not established in the EU);
- The importer (in certain circumstances); or
- Other professionals working within the supply chain of the dangerous product (and this can include distributors).
2. How do these types of liabilities apply to the manufacturers of medicines and devices?
All of the above types of liability apply to manufacturers of medicines and medical devices and allow consumers to bring product liability claims against them.
3. Does potential liability extend to the manufacturer only or could claims extend to corporate executives, employees, and representatives?
Yes, liability can extend beyond manufacturers to their employees, corporate executives and their various representatives as well others in the supply chain. For example, some offences committed by a body corporate with the consent or connivance of, or attributable to any neglect on the part of, a director, manager, secretary or other officer of the body corporate, that officer or any person purporting to act in such capacity shall also be guilty of an offence.
4. How can a liability claim be brought?
In the context of a medicinal product or medical device, a product liability claim will most likely be initiated through the filing and serving of a personal injury summons by the party bringing the claim.
Once a summons is issued, they must be personally served on defendants, within a year of their issuance, either by pre-paid post or to their place of residence or business, or to their solicitor if they have authority to accept service. Once a summons has been served, a defendant enters a memorandum of appearance and the time limit for filing a defence will depend on the court in which the particular action is taking place. In Ireland, there are mechanisms available to seek a resolution before a full hearing of the case on its merits.
5. What defences are available?
Section 6 of the Liability for Defective Products Act 1991 sets out the defences available to defendants. A producer will not be liable if they can prove:
- that he or she did not put the product into circulation, or
- that, having regard to the circumstances, it is probable that the defect which caused the damage did not exist at the time when the product was put into circulation by him or that that defect came into being afterwards, or
- that the product was neither manufactured by him for sale or any form of distribution for an economic purpose nor manufactured or distributed by him in the course of his business, or
- that the defect concerned is due to compliance by the product with any requirement imposed by or under any enactment or any requirement of the law of the European Communities, or
- that the state of scientific and technical knowledge at the time when he or she put the product into circulation was not such as to enable the existence of the defect to be discovered, or
- in the case of the manufacturer of a component or the producer of a raw material, that the defect is attributable entirely to the design of the product in which the component has been fitted or the raw material has been incorporated or to the instructions given by the manufacturer of the product.
A claim in tort will fail where the defendant can establish there was no duty of care between him or her and the plaintiff. If a duty of care did exist between the plaintiff and defendant then the plaintiff’s claim will fail if the defendant can show that said duty was not in fact breached. If the injury or loss stemming from a breach of duty was not reasonably foreseeable by the defendant, and was too remote, then the claim will fail. In order to establish causation, plaintiffs are required to demonstrate that ‘on the balance of probabilities’, the injury they sustained was as a result of the defect in the product.
The Civil Liability Act 1961 provides for the defence of ‘contributory negligence’, and this is available for defendants in a personal injury claim. Under Section 34(1), where it can be shown that the injury suffered by the plaintiff was caused partly by their own negligence, then blame and the damages recoverable will be apportioned accordingly.
Under Regulation 5 of the GPSR, if a company can prove that a product is safe and complies with any specific rules of the MS in laying down health and safety requirements that the product must satisfy to be marketed or if it conforms with the voluntary Irish standards transposing the European standards, then it may be able to resist a conviction. The Competition and Consumer Protection Commission (CCPC) is still able to take “appropriate measures” where it considers that a product is dangerous to consumers and may require its recall or withdrawal and impose restrictions on it being placed on the market.
Any defences regarding breach of contract are premised on the nature and specific terms of the contract itself.
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4. Traditional Medicines and OTC Products: Ireland
1. What are the regulatory requirements for traditional, herbal, complementary, or alternative medicines and devices?
Traditional, herbal, complementary or alternative medicines and devices on the Irish market must be either authorised or registered with the HPRA. Applications to register herbal medicinal products can be submitted under Article 8(3) or Article 10(a) of Directive 2001/83/EC. Directive 2004/24/EC on Traditional Herbal Medicinal Products was transposed into Irish law using the Medicinal Products (Control of Placing on the Market) Regulations 2007 (S.I. 540/2007). Directive 2004/24/EC requires each MS to set up a registration process for traditional herbal medicines which can be used without medical supervision. As a result of history of traditional use and acceptable safety and quality levels, traditional herbal medicinal products (THMPs) are subject to a simplified registration procedure, they must:
- be intended and designed for use without the intervention of a medical practitioner;
- be taken orally, for external use or inhalation;
- be administered exclusively at a specified strength and dose; and
- be on the market for a ‘period of traditional use’.
If herbal medicinal product does not meet the criteria for registration as a THMP, it can still be granted an MA in the same way as non-herbal medicines. Where a herbal product contains active substances in quantities deemed to have a medicinal effect, they are then classified as a medicinal product. Products which are presented as having properties for treating or preventing disease are also medicinal products. Therefore, a herbal medicinal product cannot be placed on the market unless it is the subject of either a marketing authorisation or, in the case of a THMP, a certificate of traditional-use registration granted by the HPRA.
To demonstrate ‘traditional use’, the applicant will need to prove that the THMP or a ‘corresponding product’ has been in medicinal use for at least 30 years at the time of application, with at least 15 years of this usage in the EU. And, in order to justify the proposed indication of usage, applicants are required to produce bibliographic or expert evidence documenting the traditional use of the product. The HPRA will monitor and take regulatory action (where appropriate) against unregistered THMPs found in breach of the requirements. A manufacturer of THMPs, or any other medicinal product, in Ireland is required to hold a Manufacturer’s Authorisation in accordance with the Medicinal Products (Control of Manufacture) Regulations 2007 (S.I. 539/2007).
2. Can these traditional, herbal, complementary, or alternative products be advertised directly to the public?
Yes, traditional, herbal, complementary, or alternative products can be advertised directly to the public (as long as they have certificate of traditional use registration), subject to the provisions of the Advertising Regulations. Advertisements to the public must be accurate and objective, as well as encourage rational use of the product to ensure consistency with the certificate of traditional use registration and SmPC.
3. What health, advertising, and marketing claims may be made for traditional, herbal, complementary, or alternative products?
The Advertising Regulations regulate the advertising of medicinal products and include traditional, herbal, complementary and alternative products. The Advertising Regulations prohibit the advertising of medicinal products that are not the subject of a marketing authorisation or certificate of traditional - use registration. Under Part 3, Regulation 12, in relation to the ‘form and content’ of advertisements, the Advertising Regulations stipulate that if it is a traditional herbal medicinal product, the following words must be used for making claims about the product; “Traditional herbal medicinal product for use in” followed by a statement of one or more therapeutic indications for the product compatible with the terms of the certificate of traditional-use registration for that product, followed by the words “exclusively based upon long-standing use”.
4. What are the regulatory requirements for over-the-counter (non-prescription) medications?
OTC (non-prescription) medicinal products are regulated by the HPRA. Manufacturers are obliged (as with prescription-only products) to apply for MAs in order to supply OTC products in Ireland and/or throughout the EEA. The criteria for deciding legal supply status are provided for under the Medicinal Products (Control of Placing on the Market) Regulations 2007 (S.I. 541/2007) (as amended). Generally, new medicines are only provided on prescription and manufacturers can, after a number of years of safe use, apply for reclassification to change their legal supply status.
5. Are there any limitations on locations or channels through which OTC products may be sold?
There are restrictions and regulations around the locations and channels that OTC products can be sold. Depending on their classification and legal supply status, they can either be purchased only in pharmacies or if they are available for general sale, can also be sold in supermarkets and other shops. In respect of purchasing products online and being delivered by post, the legal framework for purchasing medicines online in Ireland is set out in Directive 2001/83/EC as amended by Directive 2011/62/EC. As per Question 39, non–prescription medicines can be purchased from online retailers who display the EU ‘Common Logo’ with a link provided through the logo to the PSI’s website.
6. What health, advertising, and marketing claims may be made for OTC products?
Any health, advertising and marketing claims in relation to OTC products must be in accordance with the Advertising Regulations, and the provisions of any applicable self-regulatory codes issued by, for example, the IPHA or the ASAI.
7. Can OTC products be marketed or advertised directly to the public?
Yes. OTC products can be marketed or advertised directly to the public, but the same restrictions that are applicable to herbal medicinal products and prescription - only products apply under the Advertising Regulations.
8. What is the mechanism by which a prescription-only product can be converted to an OTC product?
In order to reclassify or ‘switch’ a product from prescription-only to non-prescription an application must be made by the MAH to the HPRA as the competent authority with responsibility for the classification/ reclassification and maintenance of a record of legal status for all authorised medicinal products. Following receipt of an expression of interest, the HPRA engages with the applicant to determine an appropriate timeframe for submission of a completed application and the supporting documentation.
Switching involves either:
- Prescription-only to pharmacy-only status; or
- Pharmacy-only to general sale status (e.g. can be sold in supermarkets).
Occasionally a product previously classified as non-prescription can be reclassified to prescription control or pharmacy-only status if new risks to the public are identified.
Prescription-only to pharmacy-only status
It must be noted that in general, switching applications are only considered for products that have a well-known and established safety profile as a prescription-only medicine. If post-marketing safety experience for a product shows that the medicinal product may be safely used without supervision by a physician, an application can be made for reclassification from prescription-only to pharmacy-only status.
Pharmacy-only to general sale status
If the benefit/risk evaluation of increased availability of a given pharmacy-only medicine is considered positive, application for general sale status can be considered. For this type of switch, sufficient evidence must be provided to ensure that such a medicine can be safely supplied without the intervention of a pharmacist.
Where products were authorised via the national procedure, an application to switch can be submitted either as a variation or a new application and if approved, the MA is updated accordingly. It must be noted that switch applications only apply to particular marketing authorisations. If a product was authorised under the MRP or DCP, any reclassification applications will require special consideration and should be discussed with the HPRA prior to submission. If Ireland is either the RMS or CMS the HPRA will need to determine whether the change can be processed nationally or whether the change in legal status needs to be submitted through an MRP or DCP process.
Each application is evaluated on a case-by-case basis and in terms of the documentation concerning safety and efficacy required to support an application for a change in the legal classification for supply varies from application to application and depends on the nature of the active substance and the extent of change proposed for the MA. The HPRA will require clinical expert reports which include benefit/risk evaluations and safety and efficacy expert reports and risk minimisation strategies. The HPRA will also require full colour mock-ups of the package leaflet and label that has been user tested to ensure that it is clear, simple and readable.
9. What are the requirements for the importation of either traditional medicines or OTC products?
The importation of THMPs or any other medicinal product, including OTC medicinal products from outside the EEA into Ireland requires a manufacturer’s/importer’s authorisation (MIA) issued by the HPRA in accordance with the Medicinal Products (Control of Manufacture) Regulations 2007 (S.I. 539/2007) (as amended). Schedule 1 of these Regulations outlines the requirements for an application to obtain a manufacturer’s/importer’s authorisation. These include requirements such as, the name and address of the applicant, and, where the applicant is not the proposed authorisation holder, the name and address of the proposed holder, a statement setting out the medicinal products and the pharmaceutical forms to which the application relates, and a statement of the manufacturing, packaging, labelling or importation operations to which the proposed authorisation relates.
Schedule 3 of these Regulations provides extensive requirements to be met by an authorisation holder for importation of medicinal products from a third country. These include providing and maintaining staff, premises, equipment and facilities necessary for the handling, control, storage and distribution of medicinal products under the authorisation, not using any other premises other than that specified in the authorisation (unless with prior approval), and maintenance of a system for recording and reviewing complaints concerning reported defects associated with any medicinal product to which the authorisation relates.
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5. Marketing, Manufacturing, Packaging & Labeling, Advertising: Ireland
1. What is the authorization process for the marketing of new drugs, biologics, medical devices, over-the-counter medications, and other medicinal products?See Question 1 of Regulatory, Pricing and Reimbursement Overview.
2. What is the authorization process for the marketing of generic versions of these products?See Question 6 of Regulatory, Pricing and Reimbursement Overview.
3. What are the typical fees for marketing approval?See Question 4 of Regulatory, Pricing and Reimbursement Overview.
4. What is the period of authorization and the renewal process?See Question 5 of Regulatory, Pricing and Reimbursement Overview.
5. What are the requirements, if any, for post-approval pharmacovigilance?
Directive 2001/83/EC and Regulation (EC) 726/2004 (as amended) outline the legal basis for pharmacovigilance for medicines intended for human use. The legislation requires MA holders (MAH) to be proactive and responsible for the on-going pharmacovigilance of their products and have in place a pharmacovigilance system. They are also required to have a qualified person within the EEA responsible for their pharmacovigilance and all relevant details must be stored on a pharmacovigilance master file.
Further to this, MA applications must have a risk management plan (RMP) outlining the risk management system put in place which must identify the safety profile of the product, as well as measures for the prevention or minimisation of risks associated with product and identify the post-authorisation obligations that have been imposed as a condition of the MA.
Device manufacturers must have systems for review of post-market surveillance data and are obliged to report incidents to competent authorities and take necessary corrective measures. They must keep a copy of the technical documentation underpinning their CE marking and it must be available for inspection by the HPRA on their request.
6. Are foreign marketing authorizations recognized?
No, medicinal products can only be placed on the market in the EEA after MAs are issued via either the Centralised Procedure or the other three MA methods outlined in Chapter 1. EU law requires that MAHs, qualified persons for pharmacovigilance and sponsors for orphan medical products must be established in the EU.
7. Are parallel imports of medicines or devices allowed?
Yes. Parallel imports of medicinal products are allowed in Ireland however a parallel import licence issued by the HPRA is required before a nationally authorised product that is parallel imported from another MS or another EEA country can be legally placed on the Irish market. The HPRA operate two different schemes in this regard: parallel product authorisation (PPA) and dual pack import registration (DPR). In either case, the parallel-imported product must have a current, full marketing authorisation in the MS or EEA country that it is being imported from. Where the imported product differs in any respect from the equivalent product on the Irish market, a PPA is required. Where the imported product is identical to the product on the Irish market, a DPR is required.
Yes. Article 16 of the MDR provides for requirements in respect of parallel trade in medical devices. Distributors or importers relabelling or repackaging devices for parallel import are required to indicate the activities that they are carrying out as well as their contact details on the device (or where that is impracticable, the device packaging) and to notify the manufacturer of the device and the competent authority of the MS where they plan to make the relabelled or repackaged device available. The distributor or importer may also be required to provide a mock-up or sample of the relabelled or repackaged device (including any translated labels or instructions for use) to the manufacturer and the competent authority upon request. There is also a requirement for the importer or distributor to submit a certificate issued by a notified body attesting that their quality management system is equipped to ensure that the requirements under Article 16 can be complied with e.g. accurate and up to date translation of information, maintenance of the safety and integrity of the device and the ability to undertake and participate in any required corrective actions taken by the manufacturer. The HPRA has not issued guidance in relation to parallel importation of medical devices however the 2021 Regulations provide for an offence where an importer or distributor fails to comply with the relevant requirements under Article 16 of the MDR.
8. What are the restrictions on marketing practices such as gifts, sponsorships, consultancy agreements, travel and entertainment, or other incentives for healthcare organizations and individual medical practitioners?
Article 94 of Directive 2001/83/EC provides rules restricting the supply of medicine samples, promotional aids, gifts, hospitality, and other incentives to healthcare organisations and medical practitioners. Where products are being promoted to medical practitioners, no pecuniary advantages or gifts can be “supplied, offered or promised unless they are inexpensive and relevant to the practice of medicine or pharmacy”. Hospitality for sales promotion events must be strictly limited to their main purpose and cannot be extended to persons other than healthcare professionals. In Ireland, the Medicinal Products (Control of Advertising) Regulations 2007 (S.I. 541/2007) (the Advertising Regulations) do not allow the supply, offer or promise of a gift, pecuniary advantage or benefit in kind to healthcare professionals, unless it is inexpensive and relevant to the practice of medicine or pharmacy. Any promotional or educational material supplied to healthcare professionals must be inexpensive, directly relevant to the practice of medicine or pharmacy, and directly beneficial to patient care.
The IPHA Code also outlines many similar provisions with further details in respect of consultancy agreements, donations and grants as well as the provision of hospitality between healthcare organisations and professionals and healthcare professionals must have regard to the ethical requirements of their own professional bodies when interacting with the medical device or pharmaceutical industries.
9. How is the manufacturing of medicines and devices regulated and by which agencies?
The manufacturing of medicines and devices is regulated by the HPRA. The Irish legislation applying to the manufacture of medicinal products is the Medicinal Products (Control of Manufacture) Regulations 2007 (as amended) (S.I. 539/2007). The HPRA issues manufacturer’s/importer’s authorisations (MIAs) to applicants who wish to manufacture or import medicinal products in Ireland. The HPRA will assess the documentation provided with the application and as part of the process may decide to inspect the site. Foreign applicants can apply for MIAs but, the HPRA can only issue MIAs for Irish manufacturing or importation sites.
As part of EU manufacturing controls, manufacturers are obliged (amongst other requirements) to abide by the principles of Good Manufacturing Practice and have a qualified person overseeing the process at all times. The HPRA undertakes the role of ensuring compliance with these obligations. As part of its role, it can conduct inspections, conduct tests and examinations and investigate compliance with authorisations.
As set out in the 2021 Regulations, the HPRA is also the competent authority in Ireland with responsibility for ensuring compliance by medical device manufacturers with the provisions of the MDR.
10. Are local manufacturing requirements compatible with Good Manufacturing Practices (GMPs) as defined by the US Food & Drug Administration (US FDA) and/or the European Medicines Agency (EMA)?
Manufacturing requirements in Ireland must be in compliance with the EU Guide to Good Manufacturing Practice (GMP). The EMA plays an important role in coordinating and harmonising GMP activities throughout the EU.
11. What is the inspection regime for manufacturing facilities?
Inspections of medicinal product manufacturing facilities are carried out by the HPRA to ensure compliance with EU pharmacovigilance obligations. Inspections by the HPRA’s GMP inspectors take place every 2 – 3 years, however the frequency of inspections may differ depending on the activities of the site and the findings of previous inspections. The objectives of pharmacovigilance inspections are as follows:
- to determine that the marketing authorisation holder has personnel, systems and facilities in place to meet their pharmacovigilance obligations;
- to identify, record and address non-compliance which may pose a risk to public health; and
- to use the inspection results as a basis for enforcement action, where considered necessary.
There are different types of inspections such as those relating to pharmacovigilance systems inspections, pre-authorisation inspections, for – cause inspections (where a trigger is recognised and an inspection is considered an appropriate way to tackle the issues), routine inspections and product – related pharmacovigilance inspections (focused on products rather than systems).
The MAH is usually notified six weeks prior to the inspection, however the HPRA has the right to either provide a shorter notice period or conduct an unannounced inspection. Inspections commence with an opening meeting conducted by the inspectors who may undertake a review of the facilities as part of the process. At the end of the inspection a final meeting is held where preliminary verbal feedback is provided. The findings are graded from “other”, minor deficiencies, major deficiencies to critical deficiencies and these are issued in a report to the company within 15 calendar days from the last day of inspection. Inspectees are required to provide a written response to the report within 35 days of the report being provided; this response should detail any measures they will be taking to address deficiencies.
The HPRA is the competent authority for medical devices in Ireland and as such can conduct post-market surveillance of products manufactured by Irish based manufacturers, as well as those placed on the Irish market. This surveillance is part of the review of the manufacturer’s compliance with the MDR, the IVDD (soon to be fully replaced by the IVDR) and related Irish legislation.
Post-market surveillance is carried out either by proactive surveillance (e.g. targeted audits for a specific category) or ‘for – cause’ audits as a result of identified issues that require follow-up in the interest of public health. Audits by the HPRA do not necessarily mean that there has been a breach of the legislation, if it is part of a proactive programme of surveillance.
The HPRA will contact the manufacturer to arrange the date, time and duration of the audit, and the manufacturer is requested to supply information in advance, such as a brief company profile, the details of the NB and relevant procedures. Similar to medicinal products, there are opening and closing meetings and at the closing meetings, any non-compliance with the relevant legislation is raised and a timeframe for corrective action agreed with the medical device manufacturer. Non-compliance is categorised as either major non-compliance or minor non-compliance.
Once there are satisfactory responses received by the HPRA in relation any non-compliance, the HPRA will issue a letter to the medical device manufacturer to that effect. However, in the event that breaches of regulations have taken place, the HPRA can choose to undertake use of its enforcement powers. As with medicinal products, the HPRA has initiated a process to conduct inspections remotely on a case-by-case basis due to the ongoing COVID-19 pandemic. The distant assessment process will, in general, follow the format for on-site inspections, although in certain circumstances, a hybrid approach of both a distant assessment and an on-site inspection of limited duration may be conducted. In such cases, COVID-19 protocols and arrangements will be agreed in advance with the manufacturer.
12. Are manufacturing facilities open for inspection by foreign inspectors or third-party inspectors as authorized by the FDA/EMA?
Yes, manufacturing facilities in Ireland can be inspected by third party inspectors on request of the EMA. The HPRA can also carry out inspections of third country manufacturers where the inspections have been delegated by a supervisory authority in another MS.
13. What are the requirements for storage, packaging, and handling of medicines and devices and their constituent components?
Storage & Handling
The Irish legislative basis for exercising control over the chain of distribution of medicinal products is Directive 2001/83/EC transposed into Irish law by Medicinal Products (Control of Wholesale Distribution) Regulations 2007 (as amended) (S.I. 538/2007). The EU has also issued ‘Guidelines on Good Distribution Practice of Medicinal Products for Human Use’ which are also to be complied with. Medicinal products should be stored and transported in conditions which ensure their quality is maintained and the products should be checked against their label requirements.
Stability testing is necessary to ensure that a product is of acceptable quality throughout its storage period and the results of stability test dictate the special storage conditions for active substances as well as for medicinal products. It is necessary to monitor compliance of the product with quality specification throughout its shelf life. Products must be stored according to conditions described on the label (e.g. “Do not refrigerate/Do not freeze”). For many medicinal products, storage and transportation temperatures are a huge factor in maintaining their quality throughout the distribution process, and one of the key requirements of a MA is that the storage conditions are met. The distribution chain may involve a number of storage and transit locations, including airports, docks, and a variety of methods of transport, including aircraft. It is therefore incumbent on manufacturers and others involved throughout the distribution network that temperatures are monitored and documented using calibrated measuring devices.
The legislation has detailed and complex requirements surrounding the distribution and transportation of ‘cold-chain’ medicinal products whilst under their care as well as requirements for controlled temperature storage. For ‘cold- chain’ products, those in the distribution process must consider issues such as:
- The nature of the products and the volumes/quantities to be stored.
- The power back-up facilities for the unit itself and for the temperature monitoring and recording system.
- The procedures for checking functionality and compliance of the unit with its temperature specifications (i.e. daily checks).
There are also various specifications relating to large and small volume operations as to their external conditions and location of thermometer(s) and so forth.
‘Controlled temperature storage’ relates to products which do not require cold storage or freezing, and unless specified in the product literature or labels, medicinal products can be sorted in room temperature conditions without compromising stability or recommended shelf life. The legislation requires temperature mapping in storage spaces (including warehouses) to ensure that all locations are likely to remain within seasonal temperature limits. If there is significant modification to the premises, there should be a repeat temperature mapping process. There should also be continuous temperature monitoring as well as daily record checking and independent reviews of these records by a Responsible Person (RP).
Where certain products require storage, handling and transportation in a frozen state (e.g. blood products), the temperature mapping exercise needs to be employed as part of a risk assessment to identify monitoring locations as well as the suitability of the unit. Temperature records must be checked daily and independently reviewed by a RP, with any deviations outside the limits documented. Temperature monitoring devices must be calibrated annually against a certified, traceable reference standard. Products should not be stored in areas shown by temperature mapping to present a risk and there must be sufficient space between the products and the internal surfaces to permit adequate air circulation.
Commission Delegated Regulation (EU) 2016/161 supplements Directive 2001/83/EC and lays down detailed rules on the safety features appearing on the packaging of medicinal products for human use. This has been implemented in Ireland by the Medicinal Products (Safety Features on Packaging) Regulations 2019 (S.I. 36/2019). Prescription medicines and some non-prescription medicines must have a unique identifier carried by a 2-d barcode and an anti-tampering device (ATD). Where medicinal products have no outer packaging, the ATD is placed on the immediate packaging and there are specific rules about how it affects the contained and its closure system(s).
The MDR set out provisions for the effective storage of medical devices. For example, Article 13(5) provides for obligations of importers to ensure that whilst devices are under their responsibility, storage or transport conditions do not jeopardise compliance with the general safety and performance requirements and comply with the conditions set by the manufacturer. Article 14(3) stipulates the same obligations for distributors of medical devices. The specifications for storage conditions are usually on the outside of containers (e.g. “store at -20° Celsius”), devices must be stored in accordance with labelled conditions. If there are no specifications regarding storage, then there are no temperature restrictions at which the device must be stored. There must be continuous temperature monitoring and this must be documented, these records should be reviewed and approved regularly to ensure compliance with the specified conditions.
Under ‘General Product and Safety Requirements’, Annex I, Chapter I of the MDR, there is a general requirement that devices shall be designed, manufactured and packaged in a way that avoids adversely affecting their intended use during transport and storage. The MDR also sets out specific packaging and labelling requirements dependent on the nature of the device. For example, in order to maintain sterile conditions for sterile devices, the following requirements must be adhered to:
- an indication permitting the sterile packaging to be recognised as such;
- a declaration that the device is in a sterile condition;
- the method of sterilisation;
- the name and address of the manufacturer;
- a description of the device;
- if the device is intended for clinical investigations, the words ‘exclusively for clinical investigations’;
- if the device is custom-made, the words ‘custom-made device’;
- the month and year of manufacture;
- an unambiguous indication of the time limit for using or implanting the device safely expressed at least in terms of year and month; and,
- an instruction to check the instructions for use for what to do if the sterile packaging is damaged or unintentionally opened before use.
Under the MDR, medical devices must be transported appropriately and in accordance with labelled storage conditions (including sterile conditions if applicable) and written procedures.
14. What information must be included in medicine and device labeling?
The HPRA has issued guidance on labels and leaflets for human medicines, and the requirements for product applications submitted after the 23 July 2007 are outlined in Directive 2001/83/EC (as amended by Directive 2004/27 EC) and transposed into Irish law by the Medicinal Products (Control of Placing on the Market) Regulations 2007 (S.I. 540/2007). The regulations applicable to products authorised prior to this date are the Medicinal Preparations (Labelling and Package Leaflet) Regulations 1993 (S.I. 71/1993). The EU has published a series of guidelines which are also applicable to labels and package leaflets and some of these are:
- Annex to the EC guideline on ‘Excipients in the labelling and package leaflet of medicinal products for human use’.
- Guideline on the Readability of the Labelling and Package Leaflet of Medicinal Products for Human Use.
- Note for guidance on Declaration of Storage Conditions A: in the Product Information of Medicinal Products B: for Active Substances.
- The presentation of the product name on the label, which must contain all elements required in Article 54. For prescription products the invented name, strength and pharmaceutical form as well as the active substances should be in that order and should include the strength of all active substances in the product where there are multiple active substances. For over-the-counter (OTC) and general sale product there is a specific format for active substances. Images should be avoided on labelling as this could interfere with readability of the name, and it is not advised to use a mixture of capital and small letters.
- Article 54 also requires that there is adequate space for labelling of the prescribed dose which should be large enough for a regular pharmacy dispensing label to be applied without obscuring the text.
- There are specific guidelines for the labelling of individual perforated blisters.
- The Directive allows the use of multilingual text with the proviso that the same text appears in all the languages used. The HPRA actively encourages the use of multilingual labelling ad packaging leaflets and there are strict criteria which multilingual packaging must fulfil.
- Labels of vaccine or plasma derived medicinal products must contain a double peel-off label to allow duplicate records to be retained of critical information. One label is to be placed on the patient’s record charts and other retained for administrative purposes to facilitate traceability of doses and the recording of batch numbers and expiry dates.
- Label and leaflet combinations present challenges in ensuring that information is presented in a legible manner. There are specific type size and fonts required under the legislation.
- The declaration of strength for liquid parenterals (quantity per millilitre and total amount per total volume) should be listed on outer and inner labels.
- The name on top of the leaflet packaging must correspond to section 1 of the SmPC (Summary of Product Characteristics).
- Technical package leaflets are not required for all products but are recommended for example, where the information is too extensive to include in the ‘take/use’ section (Section 3) of the package leaflet.
- Article 56a of Title V Directive 2001/83/EC was introduced to ensure improved access to information on medicines for people with visual impairment and thus there are extensive requirements relating to Braille on labelling and packaging. The HPRA has issued specific guidance to ensure compliance with the requirements.
- Article 56a also obliges MA holders to provide patient information leaflets in formats suitable for the blind and those who are partially sighted in order to ensure access to information on medicines.
The Medicinal Products (Safety Features on Packaging) Regulations 2019 (S.I. No. 36/2019) also gives effect to Commission Delegated Regulation (EU) 2016/161, which requires prescription medicines to carry a unique identifier 2D barcode and an anti-tampering device.
Under the MDR, all devices have to meet “General Safety and Performance Requirements” as detailed in Annex I. The MDR (Annex I, Chapter III, Section 23) sets out detailed requirements relating to the information to be supplied with devices which includes but is not limited to requirements for single-use devices, hazard warnings, electronic labelling, clinical investigations, electronic instructions for use and the introduction of mandatory symbols. There is also a requirement for a new symbol demonstrating that the package contains a medical device. The MDR has also introduced a unique device identifier (UDI) requirement for all devices manufactured in the EU.
15. What additional information may be included in labeling and packaging?
Article 62 of Directive 2001/83/EC states that outer packaging, leaflets and outer labelling can also include symbols or pictures to clarify information mentioned in Article 54 or 59(1) or any other information in line with the SmPC but cannot contain any misleading or promotional material and cannot interfere with legibility. Outer packaging and labelling can also include information for which the product has been prescribed (as long as it is in line with Article 62 of Directive 2001/83/EC).
Telephone numbers, fax numbers or email addresses are permitted as long as they are accessible to Irish patients and can be included in the printed version of the SmPC. Contact details for independent patient organisations can be included as long as they are accessible to Irish patients and are not websites.
Under Article 13(3) of the MDR, in order that their location be established, importers must indicate on the device or in an accompanying document their name, registered trade name or trade mark, their registered place of business and the address at which they can be contacted.
16. What items may not be included in labeling and packaging?
The following are not allowed on labelling and packaging of medicinal products:
- Website addresses, as references to websites, coupons, product-specific phone lines, mail clubs etc are considered to be promotional in nature and thus are not permitted. References to websites pertaining to patient organisations or for medical conditions are also not permitted. However, including the URL of the platform hosting the content of an approved mobile technology feature is permissible.
- Accreditation logos or statements e.g. ‘organic, ‘Kosher’, ‘Halal’ or ‘Guaranteed Irish’ are not permitted. The sole exception being the recycling symbol which can be used on the label or leaflet.
- Forms either in the package leaflet or coupons requesting patients to send their details for further information are considered promotional and not acceptable.
- The use of ‘New’ or ‘New product’ may not be used for promotional purposes on product labelling but can be used to alert pharmacists and patients to a change in an existing product.
17. What are the restrictions and requirements for the marketing and advertising of medicines and devices?
The advertising of human medicinal products is governed by the Advertising Regulations, which give effect to Title VIII of Directive 2001/83/EC in Ireland.
Prescription - only medicines, controlled drugs and certain sizes of non – prescription medicinal products cannot be advertised to the general public. The Advertising Regulations outline in Part 3 the provisions for advertising to the public, and in Part 4 the provisions for advertising to persons qualified to prescribe or supply medicinal products.
Advertisements to the public must be accurate and present the medicinal product objectively and encourage rational use of the product, as well as ensuring consistency with the MA and SmPC.
As per Regulation 11, Part 3 of the Advertising Regulations, an advertisement cannot be issued if it:
- gives the impression that a medical consultation or surgical operation is unnecessary, in particular by offering a diagnosis or by suggesting treatment by mail;
- suggests that the effects of taking the medicinal product are guaranteed, are unaccompanied by adverse reactions or are better than, or equivalent to, those of another treatment or medicinal product;
- suggests that the health of the subject can be enhanced by taking the medicinal product;
- suggests that the health of the subject could be affected by not taking the medicinal product;
- is directed exclusively or principally at children;
- refers to a recommendation by scientists, health professionals or persons who are neither of the foregoing but who, because of their celebrity status, could encourage the consumption of medicinal products;
- suggests that the medicinal product is a foodstuff, cosmetic or other consumer product;
- suggests that the safety or efficacy of the medicinal product is due to the fact that it is natural;
- might, by a description or detailed representation of a case history, lead to erroneous self-diagnosis;
- refers, in improper, alarming or misleading terms, to claims of recovery; and/or,
- uses, in improper, alarming or misleading terms, pictorial representations of changes in the human body caused by disease or injury, or of the action of a medicinal product on the human body or parts thereof.
The IPHA Code of Practice for the Pharmaceutical Industry also contains various requirements regarding marketing and advertising and which include Annex IV, ‘Guideline on Digital Communication in the Pharmaceutical Sector’. Some of the requirements contained in Annex IV are, for example, that every digital platform must have a homepage with links to information including an identity of the platform owner and a purpose/target audience of the platform, as well as necessitating that the sources of information provided on the digital platform, the description of persons/entities from which it was obtained, should be available on request.
Additionally, the IPHA Self-Care Advertising Code contains further restrictions and requirements in respect of the content of advertisements. This applies to consumer healthcare products and over-the-counter products, as well as traditional herbal medicinal products. The restrictions and requirements in respect of the advertising of these products include the following:
- All advertisements must be genuine, accurate and truthful.
- All advertisements must be easily intelligible to the consumer and must not mislead either directly or indirectly
- Any illustration contained in an advertisement will be regarded as an integral part of the advertisement.
- All advertising must conform both in text and illustration canons of good taste.
- Advertisements cannot offer products or treatments for diseases or conditions which require medical treatment by a healthcare professional.
- Advertisements cannot refer to chronic conditions or diagnose or prescribe treatment by correspondence.
- Advertisements cannot denigrate or unfairly attach any other products, goods or services, or make reference to competitors via brand name and induce public to think an ingredient used by competitor is unsafe or harmful.
- Advertisements must not make exaggerated claims, either direct or implied relating to curing illnesses.
- Advertisements cannot make claims on safety without qualification and cannot say there are no side effects.
- Advertisements cannot deliberately use visual or aural intimations intended to subconsciously influence consumers.
- Advertisements must not contain any reference to a doctor other than if they are registered on the Register of Medical Practitioners in Ireland, nor can they use the words “college”, “clinic”, “laboratory” or “institute” unless the facility can be shown to be in existence.
- Advertisements cannot induce or tend to induce fear or encourage unnecessary use of product.
- Advertisements cannot contain exaggerated claims or use words such as ‘magic’ or ‘mystical’ in connection with claims made for the product or treatment.
- Testimonials cannot be used except where they are the genuine views of the user and cannot be used in an advertisement for more than three years after the date on which they were produced by users.
The advertising of medicinal products is also provided for in the Advertising Standards Authority for Ireland’s Code of Standards for Advertising, Promotional and Direct Marketing (the ASAI Code). On the whole, provisions regarding the restrictions and requirements for advertising and marketing of medicinal products in the ASAI Code, the IPHA Code of Practice for the Pharmaceutical Industry, the IPHA Self-Care Advertising Code and the Advertising Regulations reflect each other in a bid to ensure consistency and clarity surrounding the promotion of medicinal products to the general public.
Medical devices being advertised in Ireland must bear a CE mark and comply with the relevant provisions of the MDR as well as other product advertising standards such as, for example, the ASAI Code.
18. Where can medicines and devices be sold or delivered? Can medicines and devices be sold or delivered via post?
Medicines and devices can be sold in pharmacies, shops and in the cases of non – prescription products and certain devices, in supermarkets. The legal framework for purchasing medicines online in Ireland is set out in Directive 2001/83/EC as amended by Directive 2011/62/EC. The Medicinal Products (Prescription and Control of Supply) Regulations 2003 as amended (S.I. 540/2003) prohibits the supply by mail order of prescription medicinal products however in certain circumstances, delivery by post or courier is permitted. Non – prescription medicines can be purchased from online retailers who display the EU ‘Common Logo’. Those selling non-prescription medicines over the internet in Ireland must also register with the pharmacy regulator, the PSI, and have their name listed on the approved Internet Supply List. A link must be provided, through the logo to the Internet Supply List on the Pharmaceutical Society of Ireland’s (PSI) website. This is to verify that the consumer is purchasing from a legitimate supplier and combat the risks of purchasing falsified medicines which may not work or be harmful to the user.
19. What are the restrictions and requirements for electronic marketing and advertising via email, by internet, social media, and other channels?
The restrictions and requirements relating to advertising of medicinal products also apply to advertising via email, the Internet, social media and other channels. That is to say, only non – prescription products can be advertised to the public. Annex IV of the IPHA Code, ‘Guideline on Digital Communication in the Pharmaceutical Sector’ aims to facilitate compliance and provide advice for the benefit of patients and healthcare professionals. The Annex states that nowhere on digital channels should there be information that could be construed as the promotion of prescription medicines, and there should be a disclaimer advising the public that the information available is not intended as substitute for a consultation with a health professional. As regards prescription medicines, the IPHA advise against the launch of digital platforms using prescription medicine names or trademarks unless specifically intended for use only by healthcare professionals.
Furthermore, it advises that companies should have clear policies in place regarding the use of social media by employees. In respect of inquiries received from healthcare professionals about product(s), responses via digital channels are only acceptable if in line with the IPHA Code. Promotion of products via electronic data communications is prohibited unless with prior permission or at the request of the recipient. In certain circumstances, it may be acceptable to contact patients through social media channels e.g. to remind them to take their prescribed medication if there is documented approval form the healthcare professional and the patient, and the material is only for the purposes of supporting patient compliance.
20. May medicines and devices be advertised or sold directly to consumers?
Yes, medicines and devices can be advertised or sold directly to consumers subject to the restrictions outlined in Questions 38, 39 and 40. Consumers are only able to purchase non – prescription only medicines over the counter (OTC) and can only obtain prescription only medicinal products with a prescription from a licensed prescriber.
21. How is compliance monitored?
The advertising and marketing of medicinal products and medical devices is governed by self – regulatory industry codes which supplement the relevant Irish and EU legislation.
The HPRA also plays a vital role in regulating and monitoring compliance with the legislation by undertaking randomised reviews of advertisements in medical journals, newspapers, radio, television and on social media. It can also carry out inspections of the offices of MAHs in Ireland. Further, the HPRA investigates any complaints they receive in relation to advertisements.
An intra-industry complaint may also be investigated by the ASAI where the interests of consumers are involved, but the ASAI has the discretion to decide to investigate or refer the complaint to a more appropriate body such as the HPRA.
The IPHA also has a role in monitoring compliance with the IPHA Code and, if there are any breaches, the IPHA Code Council will generally investigate these. The IPHA can also however, refer complex or persistent breaches to the Minister for Health, and advise the ASAI of any findings it has made against an advertiser and recommend further action.
22. What are the potential penalties for noncompliance?
There are numerous potential penalties for non-compliance with advertising legislation and codes. The HPRA can order companies to withdraw misleading advertisements and to issue corrective statements where they have published a misleading advertisement. These decisions can be appealed via the courts process. Where the IPHA consider that an advertisement is not in the interest of public and consumer safety, they can request a withdrawal of the advertisement. Additionally, if a company is convicted under the Irish Medicines Board Act 1995, the Courts can order a withdrawal of the advertisement and request issuance of a corrective statement where they are satisfied that the advertisement was misleading.
The IPHA also has a Code Committee that examines advertising complaints in detail to establish if any provisions of the IPHA Code have been breached. The penalties they can impose range from reprimands, publication of their decision, suspension or expulsion of the company in breach from the IPHA, referral to the Minister, publication of a corrective statement, and/or suspension or expulsion from the IPHA.
A breach of the Advertising Regulations can incur penalties including of fines of up to €2,500 and/or imprisonment of up to 12 months on summary conviction, a fine of up to €120,000 and/or up to 10 years imprisonment on indictment. If there are subsequent convictions, the maximum fine imposed can be up to €300,000 or imprisonment for a term not exceeding 10 years or both. If an offence is committed by a body corporate with the consent, connivance or by the negligence of a director, manager or other officer if the body corporate, that person may be held personally liable in respect of that offence. Prosecutions in relation to non-compliant advertisements can be brought by the PSI, the HSE, the Minister for Health and the HPRA.
Also from this Legal Handbook
6. Preclinical and Clinical Trial Requirements: Ireland
1. Are clinical trials required to be conducted locally as a condition (stated or implicit) for marketing approval?
Clinical trials do not have to be conducted locally in order to gain marketing approval in Ireland. All clinical trials included in applications for an MA for human use in the European Economic Area (EEA) must be conducted in accordance with Annex 1 of EU Directive 2001/83/EC which requires compliance with Directive 2001/20/EC for trials conducted in the EEA and for trials conducted outside the EEA, there must be compliance with ethical principles equivalent to those in the EEA.
In the EU, authorisation of clinical trials occurs at MS level, but the EMA plays a role in ensuring that good clinical practice (GCP) is applied throughout the EEA and compliance with the Declaration of Helsinki (1996). It also manages a database of trials carried out in the EU. In Ireland, clinical trials are governed by the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations, 2004 (S.I. 190/2004) (the 2004 Regulations). This legislation transposed the provisions of Council Directive 2001/20/EC. The new EU Clinical Trials Regulation (EU) 536/2014 was adopted on 16 April 2021, and implementation of the Regulation is planned to take place in 2022.
Once this new Regulation is implemented, Directive 2001/20/EC will be repealed, however there will be provision for a three-year transition period from the rules provided for under the outgoing Directive. Under the transition timeline, initial clinical trial applications can be made either under the Directive or the new Regulation in the first year. In year 2 all initial applications must be under the new Regulation and by year 3, all ongoing clinical trials must have transitioned onto the new Regulation. One of the main features of the new Regulation is to implement identical rules for conducting clinical trials throughout the EU. This will mean harmonisation and standardising of trials in the EU. The new Regulation also introduces a single online EU Portal and Database for clinical trials. The HPRA and the National Office for Research Ethics Committees (NREC) have also launched a National Collaboration Project to prepare for the implementation of the Clinical Trials Regulation in Ireland, which is due to run until December 2021. In preparation, a National Research Ethics Committee on Clinical Trials has been established, in respect of investigational medicinal products, which will include interventional studies and low-interventional studies involving medicinal products for human use.
2. How are clinical trials funded?
Clinical trials can be sponsored or funded by a range of parties including, pharmaceutical companies, academic or voluntary groups, clinical research centres and health care providers.
3. What are the requirements for preclinical and clinical trial protocols? Who must approve the protocols?
The HPRA issues Clinical Trial Authorisations (CTAs) to sponsors of clinical trials or persons authorised to act on their behalf prior to commencement of the trial. The sponsor or their representative must be established in the EEA and are obliged to provide the HPRA with an investigational medicinal product dossier with both clinical and non-clinical data for the product, with evidence of the Ethics Committee’s favourable opinion.
Before an application can be submitted to the HPRA, a sponsor must obtain a EudraCT (EU Clinical Trials Database) number by logging onto the EudraCT website. This number and email confirmation must be provided with the application otherwise they will not be validated. Further to this, the sponsor must register with EudraVigilance, the EEA’s system for monitoring drug safety. Lastly, there must be insurance and indemnity cover for the conduct of the trial.
4. What are the requirements for consent by participants in clinical trials?
Informed consent must be obtained by sponsors from each trial participant. Under Part 3 Schedule 1 of Statutory Instrument the 2004 Regulations there are several conditions applying to obtaining ‘informed consent’ and these are:
- The subject has had an interview with the investigator, or another member of the investigating team, in which he or she has been given the opportunity to understand the nature, objectives, risks and inconveniences of the trial and the conditions under which it is to be conducted.
- The subject has been informed of his or her right to withdraw from the trial at any time.
- The subject has given his or her informed consent to taking part in the trial.
- The subject may, without being subject to any resulting detriment, withdraw from the clinical trial at any time by revoking his or her informed consent.
- The subject has been provided with a contact point where he or she may obtain further information about the trial.
Documentary evidence in relation to the above conditions being complied with must be submitted to the Ethics Committee.
The relevant provisions of the General Data Protection Regulation (EU) 2016/679 and Data Protection Act 2018 (Section 36(2)) (Health Research) Regulations 2018 (S.I. 314/2018) (as amended) must also be complied with in respect to the processing of the data generated from a trial.
5. May participants in clinical trials be compensated?
Many participants in clinical trials in Ireland are provided with some form of compensation. Reimbursement must be reasonable but not act as an incentive. Reimbursement could be in the form of travel expenses, money or food/food vouchers as a recognition of the time sacrifice and the contribution to science made by trial participants.
6. How are participants in clinical trials protected and indemnified against any harm that arises as a result of participation in the trial?
The Irish State Claims Agency (SCA) and the IPHA have agreed a single HSE clinical trial indemnity form (CTIF) for industry – led clinical trials in Ireland. This ensures efficiency in conducting clinical trials and prevents there being numerous red tape barriers to getting approval for a trial. The CTIF is applicable to any state hospital in Ireland, and its use provides the assurance that companies sponsoring a clinical trial will adhere to certain guidelines if injury is caused to a patient as a result of their participation in the trial.
Also from this Legal Handbook
7. Regulatory, Pricing and Reimbursement Overview: Ireland
1. What are the regulatory authorities with jurisdiction over drugs, biologicals, and medical devices in your country?
The regulatory authority with responsibility for drugs, biologicals and medical devices in Ireland is the Health Products Regulatory Authority (HPRA). The HPRA is a state agency whose broad remit includes protecting and enhancing public and animal health by regulating medicines, medical devices and other health products, as well as cosmetics.
The National Standards Authority of Ireland (NSAI) is an Irish notified body designated by the HPRA to carry out conformity assessment procedures to ensure compliance with relevant legislation relating to medical devices. A notified body (NB) is an organisation designated by a European Union (EU) country to assess the conformity of certain products before being placed on the market. NBs carry out tasks related to conformity assessment procedures set out in the applicable legislation, when a third party is required. A list of NBs is published by the European Commission (EC).
The Health Services Executive (HSE) also plays a significant role in respect of drugs, biologicals and medical devices. It is charged with the provision of and running all the public health services in hospitals and communities in Ireland and is overseen by the Minister for Health. The HSE’s Corporate Pharmaceuticals Unit acts as the interface between the HSE and the pharmaceuticals industry with regards to medicinal pricing and reimbursement, and the operation of national pricing framework agreements.
2. What is the regulatory framework for the authorization, pricing, and reimbursement of drugs, biologicals, and medical devices?
In the European Union (EU), all medicines must be authorised prior to their being marketed and being made available to patients. There are four different procedures that applicants can use in order to obtain a Marketing Authorisation (MA) depending on the type of medicine and the countries the product is going to be marketed in. The four procedures are:
- Centralised Application Process
- National Procedure
- Mutual Recognition Procedure
- Decentralised Procedure
Under the Centralised Procedure (CP) applicants can make a single MA application to the European Medicines Agency (EMA); this method ensures that once granted, the MA is valid in all EU Member States (MS). The legal framework governing the CP is contained in Regulation (EC) 726/2004. Medicinal products listed in the Annex to the Regulation (EC) 726/2004 must use this procedure for authorisation. The majority of new medicines in the EU obtain authorisation via the CP.
Conversely, the majority of medicines already available in the EU were authorised at national level via national competent authorities (i.e. the HPRA in Ireland) after a full assessment. This procedure is not permitted where applicants already hold an MA in another MS. The HPRA grants MAs under the Medicinal Products (Control of Placing on the Market) Regulations 2007 (S.I. 540/2007). The HPRA in Ireland issues a MA along with a Product Authorisation (PA) number which is to be included on the box or container of the product. Details regarding applications are contained in EU Directive 2003/63/EEC and full applications must be submitted in accordance with a Common Technical Document (CTD) format.
If a company wishes to request an MA in more than one EU Member State (MS) they can do so either using the Mutual Recognition Procedure (MRP) (i.e. an MA granted in one MS can be recognised in others) or via the Decentralised Procedure (DCP) where a medicine or biological not yet authorised in the EU can be authorised simultaneously in several MS.
Mutual Recognition Procedure:
Under the MRP, a product is assessed by one MS known as a Reference Member State (RMS), and further on in the process, MAs can be sought from other MS who are known as Concerned Member States (CMS). CMS recognise the decision of the RMS rather than undertaking their own assessment process. Therefore, an applicant can hold an MA in the RMS and various other CMS. If a medicinal product is required to be authorised under the CP then this authorisation procedure cannot be used.
The Decentralised Procedure (DCP) is used by applicants to apply for MAs in more than one MS where the product has not been authorised in any MS and where applicants do not want to use the CP or the product is not eligible for the CP.
The RMS does an initial evaluation of the product and issues a draft assessment report. The other CMS either agree with this initial evaluation or ask further questions or raise objections. If any potential issues are resolved, and each application is successful then each MS involved will issue an MA for that product in their country.
‘CE’ (Conformité Européene) markings appear on many products sold in the EU. CE marking on a product is a manufacturer’s declaration that the product complies with the essential requirements of the relevant European health, safety and environmental protection legislation. Not all products sold in the EU require CE marking, however it is mandatory for medical devices and in-vitro diagnostic devices (IVDs). CE markings cannot be affixed to products until all necessary certifications have been obtained from a NB (or self-certification in some cases depending on the risk classification of the device). The HPRA has designated NSAI as a NB in Ireland to carry out conformity assessment procedures to ensure compliance with applicable medical devices legislation however manufacturers are free to choose any NB in the EU that has been legally designated to carry out the necessary conformity assessment procedure in respect of their device(s).
Directive 93/42/EEC contained the basic legal framework for the regulation of medical devices in the EU, however this has now been replaced by the Medical Devices Regulation 2017/745 (MDR). The MDR came into effect on 26 May 2021, having been postponed for a period of one year under Regulation 2020/561 due to the COVID-19 pandemic. In Ireland, the Medical Devices Regulations 2021 (S.I. 261/2021) (the 2021 Regulations) were enacted on 26 May 2021 to confer on the HPRA various regulatory functions provided for under the MDR such as classification, market surveillance, clinical investigations and enforcement. The European Union (National Research Ethics Committee for Clinical Investigations of Medical Devices) Regulations 2021 (S.I. 260/2021) have also been enacted to provide for the establishment of a National Research Ethics Committee for Medical Devices (NREC-MD), and the rules procedures applicable to its functions. An opinion from NREC-MD is required as part of the application process for clinical investigations on medical devices in Ireland.
In-Vitro Diagnostic Devices:
Directive 98/79/EC concerning In-Vitro Diagnostic Medical Devices (IVDD) provides for regulation of the safety and marketing of IVDs placed on the EU market and is transposed in Ireland using the European Communities (In-Vitro Diagnostic Medical Devices) Regulations 2001 (S.I. 304/2001). Regulation 2017/746 on In-Vitro Diagnostic Devices (IVDR) entered into force on 25 May 2017 and will take full effect on 26 May 2022. This will bring about a number of significant changes such as new classes of IVDs, there will now be four categories ranging from Class A (lowest risk), to Class D (highest risk). Further, the IVDR also expanded the definition of an IVD to include software, introduced a unique device identifier (UDI) for each device to enhance traceability, as well as making it obligatory for IVDs and testing services offered online to comply with the IVDR the moment they are offered for use in the EU. Owing to concerns over market disruptions expected to be caused by a lack of appropriately designated notified bodies, the European Commission has recently proposed an extension of the 2-year transition phase currently provided for under the IVDR. Under this proposal, the highest risk devices (Class D) would have until May 2025 to undergo conformity assessment by a notified body. Moderate-risk devices (Class C) would have until May 2026 and lower risk Class B and Class A sterile devices would have until May 2027.
Pricing & Reimbursement:
In Ireland, the HSE has statutory responsibility for medicine and medical device pricing and reimbursement under the Health (Pricing and Supply of Medical Goods) Act 2013 (the 2013 Act). The 2013 Act requires the HSE to maintain a list of reimbursable items (the Reimbursement List) and there is a standardised application procedure that must be used by suppliers in order to have most products (other than those restricted to hospital or medical specialist use) included on the Reimbursement List. Ireland does not have a distinct approval procedure for reimbursements for rare disease medicines or hi – tech products, however applications in respect of cancer drugs involve specialist review by the National Cancer Control Programme Technology Review Committee (NCCP-TRC).
The 2013 Act outlines the criteria for decisions regarding the reimbursement of medicines and medical devices. The decisions made by the HSE are also informed by recommendations and analyses provided by the National Centre for Pharmacoeconomics (NCPE). An important metric used by the NCPE and the HSE to assess the cost effectiveness of a medicine is the Incremental Cost Effectiveness Ratio (ICER) of the medicine per Quality Adjusted Life Year (QALY). Where a medicine is considered by the NCPE to be cost-effective, the HSE may approve it for placement on the Reimbursement List. Alternatively, the HSE can request a further review of the application by the HSE Drugs Group, whose recommendation is then considered by HSE senior leadership in order to make a final decision on whether or not to place a medicine on the Reimbursement List.
In 2016 the Irish government also entered into a framework agreement with the Irish Pharmaceutical Healthcare Association (IPHA) for the supply and pricing of medicines (the Framework Agreement). Taken together, the 2013 Act and the Framework Agreement provides for a system for setting the reimbursement price for drugs. Although the Framework Agreement was scheduled to expire in 2020, an extension to the end of July 2021 was agreed owing to the need to prioritise responses to the Covid-19 pandemic. An updated agreement is currently being negotiated however at the time of writing the status of the Framework Agreement as remaining in force pending the outcome of those negotiations is uncertain and it is not clear if the Framework Agreement has now formally expired or when a new agreement will be announced.
The Medicinal Products (Control of Placing on the Market) Regulations 2007 (S.I. 540/2007) outlines the requisite criteria for establishing the legal supply status of medicinal products. The two main categories of medicinal products are prescription – only and non – prescription products. New medicines generally may only be supplied on prescription; however when/if the medicine has a well-known, long established safety profile and there is evidence that the medicinal product may be safely used without supervision by a physician, an application can be made for reclassification from prescription-only medicine to pharmacy-only status.
Generally, the Irish State will only reimburse prescription – only products, however non – prescription items, such as generally available painkillers, can be reimbursable where prescribed by a doctor. The State operates the following four principal reimbursement schemes:
- General Medical Services Scheme: this is a means – tested scheme and patients pay €1.50 per item prescription and this goes up to a maximum of €15 per family per month. Pharmacists obtain dispensing fees but no mark – up fees.
- Long Term Illness Scheme: this applies to specific long-term conditions such as epilepsy and diabetes. Patients receive medicines free of charge and pharmacists receive a mark - up and dispensing fee.
- Hi – Tech Scheme: patients receive expensive medicines required for long – term care and, if they hold a medical card or the medicine is a specific condition under the Long-Term Illness Scheme they receive the medicine free of charge. Alternatively, they pay the first €114 a month as per the Drug Payment Scheme (see below).
- Drug Payment Scheme: patients pay a maximum of €114 per month and pharmacists receive a mark - up and dispensing fee.
3. What are the steps to obtaining authorization to develop, test, and market a product?
In Ireland, authorisations to market new medicinal products are granted by the HPRA under the Medicinal Products (Control of Placing on the Market) Regulations 2007 (S.I. 540/2007). An Irish authorisation for a human medicinal product is called a product authorisation (PA). Details on the content of an application are outlined in Directive 2003/63/EEC.
4. What are the approximate fees for each authorization?
The HPRA’s website provides a spread sheet listing numerous fees for varying applications and some of these are as follows:
- Authorisation of Medicines (new National Application) - €20,400
- Authorisation of Medicines (new Mutual Recognition Concerned Mem-ber State Application) - €14,280
- Authorisation of Medicines (new Mutual Recognition Reference Member State Application) - €15,300
- Authorisation of Medicines (new Decentralised Concerned Member State Application) - €20,400
- Authorisation of Medicines (new Decentralised Reference Member State Application) - €51,000
5. For how long are marketing authorizations/registrations valid? How are marketing authorizations/registrations renewed?
Marketing authorisations are valid for a period of five years from the date of issue. In order for MAs to remain valid, renewal applications must be made to the HPRA at least nine months before expiry of the existing authorisation. Following renewal, the authorisation remains valid for an indefinite period unless further renewals are considered necessary on drug safety grounds.
For products authorised using the Centralised Procedure (see above) renewal applications must be submitted to the European Medicines Agency (EMA).
6. How does the authorization process differ between brand- name products and generic products? Are there differences for local manufacturers versus foreign-owned manufacturers?
Brand-name & Generic Products:
Depending on the data submitted in an application for authorisation, medicines are classified into two main types, reference and generic (interchangeable) medicines. The data requirements for these are harmonised in law across the European Community and the definitions of these medicines are outlined in EU legislation (Directive 2001/83/EC).
A reference medicine is one that has been authorised following the submission of a dossier containing full pharmaceutical, pre-clinical and clinical trial data. These medicines are also called branded, originator or proprietary medicines. Following authorisation, they are entitled to a ten-year period of market protection prior to the introduction of a generic medicine.
A generic medicine contains the same quantity of active substance and is used in the same dose to treat the same condition as a reference medicine. It must meet the same standards of quality and safety and have the same effect as a reference medicine. However, the data submitted for authorisation of a generic medicine is reduced and there is scope for applicants to omit some or all of the preclinical and clinical data. The dossier for a generic application must contain full pharmaceutical data and the clinical data may include a study demonstrating bioequivalence with the reference product, however in certain circumstances a waiver of bioequivalence can be submitted.
The requirements for bioequivalence data are harmonised across the EU. A bioequivalence study is performed in healthy volunteers who receive single doses of the reference and generic medicine and blood samples are taken to determine the handling of the medicines by the body. The reference and generic medicines are considered “bioequivalent” when they produce the same plasma concentration of active substance in the body when tested. When a generic medicine is demonstrated to be bioequivalent to a reference medicine, the benefits and risks of both medicines are considered the same and the generic medicine can usually be substituted for the reference medicine. Where bioequivalence cannot be demonstrated, bridging data is required to demonstrate that the differences do not affect the product’s safety and effectiveness.
Local Manufacturers versus Foreign–owned Manufacturers:
As discussed in Question 2, there are four methods of obtaining an MA and these are as follows:
- Centralised Procedure
- National Procedure
- Mutual Recognition Procedure
- Decentralised Procedure
7. How are combination products (drug + drug, drug + biologic, drug + device, biologic + device, drug + biologic + device) regulated?
As per the EMA’s guidelines, medicines can be marketed for use in combination with a medical device, usually to enable the delivery of the medicine. However, the specific manner in which any given drug-device combination will be regulated depends on the nature of the combination and the respective roles of the drug and device elements. If the principal intended action of the combination product is achieved by the medicine component, the entire product will ordinarily be regulated as a medicinal product under Directive 2001/83/EC or Regulation (EC) 726/2004. The two types of combination product are as follows:
- Integral – medicinal product and the device form a single integrated product for example single dose pre-filled syringes, pens and injectors and;
- Co- packaged – the medicinal product and the device are separate items contained in the same pack. For example, an injection pack which has separate needles and filter needles.
Article 117 of the MDR has also introduced new rules for drug-device combinations which are applicable in Ireland. Article 117 amends Directive 2001/83/EC and provides that authorisation applications for integral drug-device combinations shall be subject to the MDR and should include evidence of the conformity of the device element of the combination with the relevant requirements (General Safety and Performance Requirements) contained in Annex I of the MDR. This can take the form of a certificate of conformity issued by a notified body or a Notified Body Opinion (NBOp) as necessary. The EMA has published guidance such as a Q&A on Implementation of the Medical Devices and In Vitro Diagnostic Medical Devices Regulations ((EU) 2017/745 and (EU) 2017/746) (Rev. 2) and a Guideline on quality documentation for medicinal products when used with a medical device to assist stakeholders in ensuring compliance with these requirements.
8. How is compliance with regulations monitored and evaluated? Is the regulatory regime comparable with the U.S. Food and Drug Administration or the European Medicines Agency expectations and requirements?
In Ireland, compliance with regulatory requirements is monitored and evaluated by the HPRA in accordance with EU legislation and regulations which include EMA expectations and requirements. The HPRA as the national competent authority has the requisite statutory authority for oversight of the regulation of the pharmaceutical, medical device and IVD industries and is active in its role of ensuring regulatory compliance by stakeholders.
9. What is the potential range of penalties for noncompliance?
The Irish Medicines Board Act 1995 (as amended by the Irish Medicines Board (Miscellaneous Provisions) Act 2006)(the 1995 Act), provides for the HPRA (formally known as the Irish Medicines Board) to appoint authorised officers who have a wide range of investigatory powers that may be exercised in the course of an investigation, inspection or any other function undertaken under the 1995 Act or the various regulations made under the 1995 Act.
Section 32 of the 1995 Act also confers extensive powers on the Minister for Health to make regulations for the purposes of the Act. Section 32(4) of the Act makes it an offence to contravene any regulation made under Section 32. The HPRA can bring summary proceedings for an offence under the 1995 Act; the time limit for prosecution is two years from the date of the offence. In cases of more serious offences where summary proceedings are not appropriate, trial will be on indictment by direction of the Director of Public Prosecutions and the penalties for conviction are:
- First offence: a fine not exceeding €120,000 or imprisonment for a term not exceeding ten years or both.
- Subsequent offence(s): a fine not exceeding €300,000 or imprisonment for a term not exceeding ten years or both.
If an offence is committed by a body corporate with the consent, connivance or by the negligence of a director, manager or other officer of the body corporate, that person may also be found to be personally liable in respect of that offence. The HPRA carry out investigations relating to illegal supply, manufacture or advertising of health products and they prosecute where they have detected a significant risk to public health or where compliance cannot be achieved or if there are other aggravating factors. They also liaise with other national agencies including the police and Customs as well as with their international counterparts where necessary.
The IPHA also operates a self-regulatory code, the Code of Practice for the Pharmaceutical Industry (the IPHA Code), which IPHA members undertake to adhere to. In cases of proven breaches of the IPHA Code by members, the IPHA Council can opt for a range of penalties including (but not limited to), reprimanding the member company for breach of the IPHA Code; asking the member company to cease the practice which brought them into breach; and/or recommending to the IPHA Board of Directors that the member company be suspended or expelled from the IPHA. They may also opt to charge administrative fees, and their findings are published annually and made available to IPHA members as well as the HPRA and the Minister for Health.
The HPRA also has responsibility for ensuring that medical devices legislation is complied with. The 2021 Regulations set out a range of general offences related to the oversight of medical devices in Ireland, as well as lists of offences that are specific to manufacturers, importers, distributors, authorised representatives, notified bodies and the sponsors of clinical investigations.
Proceedings in relation to a summary offence under the 2021 Regulations may be brought and prosecuted by the HPRA. As the 2021 Regulations were made under section 32 of the 1995 Act, the same penalty range will apply for medical device offences as for those relating to medicines. If an offence is committed by a body corporate with the consent, connivance or by the negligence of a director, manager or other officer of the body corporate, that person may be held to be personally liable in respect of that offence. Any person or body corporate found guilty of an offence will be liable on summary conviction and can be subject to six months imprisonment, a fine, or both.
There are also potential penalties under the Irish Medtech Code of Ethical Business Practice, which, similar to the IPHA Code, is a self-regulatory code operated by the Irish MedTech Association. In cases of proven breaches by its members, the Irish Medtech Association can decide to issue a formal letter of reprimand, issue a letter of reprimand and recommend suspension of the member company from the Irish Medtech Association (with various conditions) or recommend expulsion from the Irish Medtech Association.
10. Is there a national healthcare system? If so, how is it administered and funded?
In Ireland, national healthcare policy and expenditure is determined by the Department of Health under the guidance of the Minister for Health and is funded by an annual government budget. Public healthcare services are provided by the HSE which owns and runs public hospitals. The HSE was established under the Health Act 2004 as the single body with statutory responsibility for management and delivery of health and personal social services in Ireland. Every resident in Ireland is entitled to subsidised or free approved prescribed medicines as well as certain medical aids and appliances.
11. How does the government (or public) healthcare system function with private sector healthcare?
The Irish healthcare system is two tiered, comprising of the public healthcare service which is administered by the HSE, and the private healthcare system which is funded by private funds and private insurance. There are also voluntary public hospitals and the majority of their income comes from State funds. They are sometimes owned by private bodies such as religious orders. In practice, public hospitals and public voluntary hospitals are not different and most of them offer private healthcare, but there is a clear distinction between public and private beds. There is a set daily charge for private patients in public hospitals.
Private hospitals operate purely independently of state health service, and patients who opt to go private must pay (or their insurance company must pay) for the full cost of their treatment. Private hospitals are free to set their charges to their patients at rates of their own choice. As of the end of 2020, almost half of the Irish population held private health insurance and can avoid the potential for lengthy waiting lists associated with public health services
12. Are prices of drugs and devices regulated and, if so, how?
Where reimbursement is not being sought, a price does not need to be agreed by the HSE for a medicine or medical device prior to it being placed on the Irish market. Generally speaking, and as outlined in Question 2 under ‘Pricing and Reimbursement’, the reimbursement prices of drugs and medical devices are considered by the HSE in line with Health (Supply and Pricing of Medical Goods) Act 2013 and the associated IPHA Framework Agreement where manufacturers (or others in the supply chain) are seeking reimbursement.
13. How are the drugs and devices used by patients paid for? What roles do public and private payers play?
If you are ordinarily resident in Ireland, then you may be eligible for free or subsidised prescribed drugs and medicines as well as certain medical and surgical aids and appliances. As outlined in Question 2, there are four principal means-tested reimbursement schemes run by the State under which patients can receive free or subsidised drugs, medicines and aids and appliances. The HSE Primary Care Reimbursement Scheme provides for a Reimbursement List of medicines or aids, which will be free or subsidised for holders of a HSE Medical Card or if provided under a HSE scheme.
Medical card holders who are prescribed items that are not on the Reimbursement List can apply for a discretionary hardship scheme. Furthermore, under the reference pricing system established by the 2013 Act, where a medicine is interchangeable, the HSE will pay the reference price if you have a Medical Card. That is to say, where generic medicines have been deemed interchangeable with brand name medicines, the HSE will establish a reimbursement price for these grouped medicines, and this will be the group reference price. If you are a holder of a Medical Card and seek a medicine deemed interchangeable, the HSE will reimburse this reference price. However, if you wish to choose a more expensive medicine, you must pay the difference between the reference price and the retail price. Medical aids and appliances are usually free to medical card holders and those who do not have a medical card often get their aids for free if the aids are required as part of hospital treatment. If someone does not hold a Medical Card, they can apply to their local health office for a contribution towards the price. Furthermore, health insurers will also often refund part of the cost of surgical or medical aids.
14. Who dispenses drugs and devices to patients and how are those dispensers compensated?
Drugs dispensed in the community are funded by the State through reimbursements of pharmacists where patients are covered by a reimbursement scheme and where the product being dispensed is on the Reimbursement List. Payments are regulated by the Public Service Pay and Pensions Act 2017 (Payments to Community Pharmacy Contractors) Regulations 2019 (S.I. 639/2019) and HSE Community Pharmacy Contractor Agreements. In general, all pharmacies have agreements with the HSE under the Primary Care Reimbursement Services Scheme to dispense approved drugs and medicines. General Practitioners (GPs) can also provide drugs and medicines directly to patients in circumstances where there is only one practice centre which is three or more miles from a retail pharmacy.
The HSE reimburses medical devices (that are on the Reimbursement List) via their Aids and Appliances Schemes. Hospitals and other specialist institutions provide the aids and appliances (as well as drugs and medicines) directly to patients.
15. What are the professional and legal responsibilities of those who dispense drugs and devices? What role do they play in providing patient care, information, and safety?
Medical practitioners and pharmacists commit themselves to abiding by and adhering to the ethical guidelines and professional standards set by their statutory regulators. Medical practitioners in Ireland must adhere to the provisions of the Medical Practitioners Act 2007 (as amended) as well as the Medical Council’s Guide to Professional Conduct and Ethics for Registered Medical Practitioners (the Ethical Guide). Pharmacists are obliged to adhere to the provisions of the Pharmacy Act 2007 (as amended) as well as the Pharmaceutical Society of Ireland’s Code of Conduct (the Code of Conduct).
Both the Ethical Guide and Code of Conduct require compliance by medical practitioners and pharmacists with medicines legislation. Regulation of the sale and supply of medicinal products is provided for under the Medicinal Products (Control of Advertising) Regulations 2007 (S.I. 541/2007) and the Medicinal Products (Prescription & Control of Supply) Regulations 2003 (S.I. 540/2003). Regulation of the supply of controlled drugs is also legislated for under the Misuse of Drugs Acts and more specifically, the Misuse of Drugs Regulations 2017 (S.I. 173/2017).
The Pharmaceutical Society of Ireland (PSI) and the Medical Council have also issued joint guidance regarding the safe prescribing and dispensing of medicines. The joint guidance lists the following respective obligations:
- Provide a valid prescription which meets the requirements of the legislation.
- Be satisfied as to the identity of the person for whose treatment the prescription is to be issued.
- Follow relevant national and international prescribing guidelines.
- Within reason, be available to confirm or discuss any matters related to the prescription and the patient.
- Ensure the safe keeping of prescription pads to reduce the risk of theft and forgery.
- Facilitate appropriate withdrawal of controlled drugs and follow-up and refer as necessary.
- Only dispense on the basis of a legally valid prescription.
- Be satisfied that the signature of the prescriber is genuine.
- Prior to supply, be satisfied as to the identity of the person or bona fide representative presenting the prescription or collecting controlled drugs.
- Be vigilant for forgeries or unusual prescribing patterns.
- Store controlled drugs in a safe manner, in accordance with the relevant legislation.
- Record all supplies of schedule 2 controlled drugs (Misuse of Drugs Regulations 2017) in the pharmacy’s controlled drugs register.
- Communicate with the medical practitioner if there is any query about the prescription or care of the patient.
- Adhere to national guidelines and facilitate appropriate withdrawal of controlled drugs and follow-up and refer as necessary.