Medicines Authorisations

Medical Product Authorisation

A medicinal product is any substance or combination of substances presented as having properties for treating or preventing disease in human beings or any substance or combination which may be administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action or making a medical diagnosis.

The placing of medicinal products on the market is subject to EU-wide controls. There are equivalent controls in respect of medical devices, cosmetics, foods, and biocides.

The Irish Medicines Board was formerly the regulatory body. It was reconstituted as the Health Products Regulatory Authority.

A medicinal product may not be placed on the market unless it has a marketing authorisation, Community marketing authorisation granted by the EU or a certificate of registration or certificate of traditional use registration. Product authorisations are given a code, commencing PA or in the UK a product licence PL.

It is an offence for a person in the course of a business to sell, supply, manufacture, or have in his possession a medicinal product unless he or she reasonably believes that it has been or is intended to be placed on the market on foot of a marketing authorisation or certificate.

Herbal & Homeopathic

Herbal medicinal products may obtain a marketing authorisation in the same way as a medicinal product. Certain traditional herbal medicinal products may obtain a certificate of traditional use registration. This has less onerous criteria in terms of application and compliance. It applies only to some types of herbal medicines.

Homoeopathic medicinal products may be licensed as medicinal products or under the regulator’s homoeopathic medical products National Rule Scheme in Ireland. This only applies to products typically used in homoeopathy in Ireland, which do not require a prescription or supervision.

Labelling authorisations are required. An alternative is a certificate of registration under a simplified registration procedure, which requires less input and proof.

Authorisations Exceptions

The Department of Health may temporarily authorise the distribution of medicines that would be otherwise unauthorised in relation to outbreaks or suspected outbreaks of pathogenic agents, toxins, chemical agents or nuclear radiation.

The product licence requirements do not apply to

• investigational products,
• certain exempt products,
• importation from outside the EU for personal use other than a mail-order basis,
• supply of an exempt medicinal product.
• supply or sale of an unauthorised product in response to a bona fide unsolicited offer, formalised in accordance with the specification of a registered medical practitioner or dentist for use by his individual patients under his direct responsibility to fulfil special medical needs. This is subject to various conditions.
• a registered medical practitioner or dentist procuring or manufacturing stock of medicinal products for administration limited to volume and weight.
• activities in pharmacy in relation to procuring the manufacture of a stock of medicinal products.
• supply of non-prescription medicines to a person exclusively for use in the course of his business for the purpose of administration to one or more human beings other than by sale.
• preparation of a medicinal product that is radiopharmaceutical at the time it is intended to be administered by or under the responsibility of a person by whom it is to be administered in accordance with the manufacturer’s instruction exclusively from an authorised kit, generator or precursor from an establishment licenced by the Radiological Protection Institute of Ireland in that regard.

Approval Application

The application for licensing requires a detailed application, details of trials and studies, and analysis. A dossier is submitted to the regulator. Procedures are to be followed.

The approval is made on the basis of favourable, benefit v risk analysis relative to specific criteria regarding quantity, safety, efficacy of the products and proposed conditions of use.  The authorisation may be issued subject to conditions, including restrictive conditions requiring warnings, etc.

A marketing authorisation certificate is valid for up to five years, after which it must be renewed. A variation requires further application.

The HPRA has the power to vary or revoke a marketing authorisation or certificate at the request or on its own initiative. Special provisions apply in relation to urgent safety restrictions.

The marketing authorisation is accompanied by a summary of product characteristics. This contains detailed particulars regarding the therapeutic uses, dosage, and safety in uses based on the analysis of the data submitted. The format is prescribed by legislation.

Ongoing Obligations

Authorisation or certificate holders and persons acting on their behalf in placing products in the market must ensure, within the limits of their responsibility, appropriate and continued supplies of products to pharmacies and other persons authorised.

In several of the above later categories, there are obligations to keep extensive records for a period, often five years, dealing with the source of the product, quantity of supply, persons to whom supply was made, batch number, and details of any suspected adverse reaction.

Generic Medical Products

A generic medicinal product is one that contains the same active ingredients in the same quantities as an original reference medicinal product. A generic medicine must be bio-equivalent to the original product in order to be approved. It is not required to provide results of clinical and preclinical studies; evidence of bioequivalence is required.

Data obligations apply. Where the product does not fall within the definition of the generic medicinal product or where bioequivalence cannot be demonstrated, data from preclinical tests and clinical trials must be furnished.

The marketing authorisation prohibits generics to be placed on the market for 10 years.

EU Parallel Imports

EU treaty rights have recognised the right to parallel import equivalent products into the state that are lawfully in the market in other EU states. The regulatory authority grants parallel import licences.

It is a marketing authorisation or certificate of traditional use registration with respect to imports from another state. Where the product differs from the version on the Irish market, a parallel product authorisation is required. Where it is identical, a dual import registration may be granted.

Pharmacopoeia

The European Pharmacopoeia operates under a convention promoted by the Council of Europe, dating back to the 1960s. It was later adopted by the EU itself and now has 37 members.

European Pharmacopoeia monographs are mandatory for parties to the European Pharmacopoeia Convention. The British Pharmacopoeia was designated as the official Pharmacopoeia by Ireland by the 1931 Act. In 1976, Ireland became a party to the Convention, and the European Pharmacopoeia became the official Pharmacopoeia.

The Irish regulator provides the Secretariat for the Irish Pharmacopoeia and deals with the Irish delegations to the European Pharmacopoeia Commission.

Pharmacovigilance

Pharmacovigilance involves the continued monitoring of products through their life cycle. The legal framework is set out in the EU regulations.

A person placing a medicine in the market must have a qualified person for pharmacovigilance. They must keep details of suspected adverse reactions and file them with the European Medical Authority and Irish regulator.

They must submit details of all adverse reactions that come to their attention. They must collect additional pharmacovigilance information.

Clinical Trials

EU Directive on Clinical Trials implemented through regulations supplements and largely replaces the Control of Clinical Trial Act. Products used in clinical trials may include new products or variations from those authorised.

An ethics opinion committee is required from the regulator before conducting and a consent before conducting a trial. There are provisions regarding the manufacture, importation, supply and labelling of investigational medical products. They deal with pharmacovigilance and need to comply with good clinical practice and manufacturing practices.

There are provisions in relation to the establishment of an ethics committee. They must be independent, comprising healthcare professionals and lay persons. They must confirm the suitability of the protocol and investigators, adequacy of facilities, appropriate insurance, indemnity compensation, etc.

Medical trials must be conducted in accordance with internationally recognised ethical and scientific quality requirements. There are requirements for reporting and recording clinical trials involving humans.

There are detailed provisions regarding consent due by participants, including in particular with reference to children and persons who lack capacity.

There are exceptions for doing interventional studies and trials, which is where the products and medicinal products are prescribed in the usual manner in accordance with the marketing authorisation.