Quality of the medicinal products. Drug switching. Social Pharmacy - Lecture 09 Authorisation of medicinal products (in the EU). Institutional framework. Authorisation procedures. Quality of the medicinal products. Drug switching. JAMASOFT2017

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To guarantee the highest possible level of public health and to secure the availability of medicinal products to citizens across the EU, all medicinal products for human use have to be authorised either at Member State or Community level before they can be placed on the EU market. JAMASOFT2017

The authorisation is based on the evaluation of the quality, safety and efficacy of the medicinal product and the assessment of its benefit and risk. JAMASOFT2017

The particulars and documents which must accompany an application for the authorisation for a medicinal product demonstrate that potential risks are outweighed by the therapeutic efficacy of the product. JAMASOFT2017

Competent authorities to grant an authorisation in the EU are national governmental institutions „medicines agencies“ and 2. the European Commission (decision making) in collaboration and shared responsibility with the European Medicines Agency (application and documentation evaluation). JAMASOFT2017

Authorisation of medicinal products in the EU Main stakeholders in the process are - patients and consumers, - healthcare professionals, - healthcare providers, payers (insurance companies) and - applicants (pharmaceutical companies). JAMASOFT2017

The pharmaceutical industry makes an important contribution to Europe's and the world's well-being. It is a strategic sector due to its economic as well as its public health dimension. JAMASOFT2017

Life cycle of a medicinal product: Research and development, Manufacturing Authorisation application: benefit-risk Obligations of the authorisation holder Post-marketing surveillance: quality and safety (pharmacovigilance) Variations in the authorisation Validity of the authorisation and renewal JAMASOFT2017

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The authorisation procedures The European system for the authorisation of medicinal products for human and animal use was introduced in January 1995 with the objective of ensuring that safe, effective and high quality medicines could quickly be made available to citizens across the European Union. JAMASOFT2017

EMA JAMASOFT2017

The European Medicines Agency is a decentralised agency of the European Union, located in London. The Agency is responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the European Union. JAMASOFT2017

centralised procedure decentralised procedure The European system offers several routes for the authorisation of medicinal products: centralised procedure decentralised procedure mutual recognition procedure purely national procedure (one member state only) JAMASOFT2017

The Centralised Procedure. Applications for the centralized procedure are made directly to the European Medicines Agency which issues and Opinion resulting from the scientific assessment of the quality, safety and efficacy of medicinal products and further may lead to the granting of an European marketing authorisation by the Commission which is binding in all Member States. JAMASOFT2017

The Decentralised Procedure which was introduced with the legislative review of 2004, is also applicable to the majority of conventional medicinal products. Through this procedure an application for the marketing authorisation of a medicinal product is submitted simultaneously in several Member States, one of them being chosen as the "Reference Member State". At the end of the procedure national authorisations are granted in the reference and in the concerned Member States. JAMASOFT2017

The Mutual Recognition Procedure which is applicable to the majority of conventional medicinal products, is based on the principle of recognition of an already existing national authorisation by one or more Member States. JAMASOFT2017

Special rules exist for the authorisation of medicinal products for paediatric use, orphan drugs, advanced therapy, traditional herbal medicinal products, vaccines, homeopathics. JAMASOFT2017

A homeopathic medicinal product. Only homeopathic medicinal products which satisfy all of the following conditions may be subject to a special, simplified registration procedure: administered orally or externally no specific therapeutic indication appears on the labelling there is a sufficient degree of dilution to guarantee the safety of the medicinal product. JAMASOFT2017

Authorisation procedures. The national authority closely examines the efficacy, risks and quality of the medicine. All important data about the medicine is reproduced in the detailed product information sheet for doctors and pharmacists (summary of product characteristics, SPC). A summary for patients is also made, in the form of a package leaflet. The national authority also decides on the product's legal status. (whether it can be obtained without prescription or may only be dispensed on prescription). JAMASOFT2017

Once a medicine has been marketed, the national authority continues to monitor the medicine‘s Adverse Event Reports. It therefore always contains the most up-to-date information about the efficacy and possible adverse events of medicines. If necessary, the authority can take steps like modifying the package leaflet text or in the most extreme case - suspending sales or even withdrawing the medicine from the market entirely. JAMASOFT2017

The authorisation shall be refused, if it is clear that: (a) the risk-benefit balance is not considered to be favourable, or (b) its therapeutic efficacy is insufficiently substantiated by the applicant, or (c) its qualitative and quantitative composition is not as declared. JAMASOFT2017

Medicinal product information is an integral part of the authorisation! Information intended for healthcare professionals, ongoing harmonisation in the EU therapeutic indications, posology and methods of administration, contra-indications, special warnings and precautions for use, interactions with other medicinal products, use during pregnancy and lactation, effects on ability to drive and to use machines undesirable effects, overdose, pharmacological (pharmacodynamic, pharmacokinetic) properties, preclinical safety data, pharmaceutical particulars. JAMASOFT2017

The official contents of Summary of Product Characteristics (SPC): 1. Name of the medicinal product 2. Qualitative and quantitative composition 3. Pharmaceutical form 4. Clinical particulars 4.1 Therapeutic indications 4.2 Posology and method of administration 4.3 Contraindications 4.4 Special warnings and precautions for use 4.5 Interaction with other medicinal products and other forms of interaction 4.6 Fertility, pregnancy and lactation 4.7 Effects on ability to drive and use machines 4.8 Undesirable effects 4.9 Overdose 5. Pharmacological properties 5.1 Pharmacodynamic properties 5.2 Pharmacokinetic properties 5.3 Preclinical safety data 6. Pharmaceutical particulars 6.1 List of excipients 6.2 Incompatibilities 6.3 Shelf life 6.4 Special precautions for storage 6.5 Nature and contents of container 6.6 Special precautions for disposal and other handling 7. Marketing authorisation holder 8. Marketing authorisation number(s) 9. Date of first authorisation/renewal of the authorisation 10. Date of revision of the text JAMASOFT2017

Patient information leaflet (PIL) Braille Medicinal product information as an integral part of the authorisation. Patient information leaflet (PIL) Braille Challenges of multilingual texts JAMASOFT2017

Quality of the medicinal product. The application shall be accompanied by the following particulars and documents: - description of the manufacturing method, - description of the control methods employed by the manufacturer, - a document showing that the manufacturer is authorised in his own country to produce medicinal products. JAMASOFT2017

Quality of the medicinal product Member States shall take all appropriate measures to ensure that: (a) the competent authorities verify that manufacturers and importers of medicinal products coming from third countries are able to carry out manufacture in compliance (b) the competent authorities may allow manufacturers and importers of medicinal products coming from third countries, in justifiable cases, to have certain stages of manufacture and/or certain of the controls referred to in (a) carried out by third parties; in such cases, the verifications by the competent authorities shall also be made in the establishment designated. JAMASOFT2017

Good Manufacturing Practice (GMP) is defined as „That part of Quality Assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use.“ The competent authority may also carry out unannounced inspections at the premises of manufacturers of active substances used as starting materials, or at the premises of the authorization holders whenever it considers that there are grounds for suspecting noncompliance with the principles and guidelines of Good Manufacturing Practice. JAMASOFT2017

Authorisation and Switching of Medicine-Status: from Prescription-only To Over-the-counter availability. JAMASOFT2017

In order to market a medicinal product a manufacturer must first obtain regulatory approval by conducting clinical tests and trials to prove that the product is safe and effective. JAMASOFT2017

Producers of generic medicines are able to use the original manufacturer's approval if they can demonstrate, that the generic version is bioequivalent to the approved medicine. JAMASOFT2017

Facilitating generic drug manufacturing. Drug Switching. As the global disease burden expands, the need for new, more effective treatments is greater than ever. Investing in drug research and development is, however, a costly, high-risk endeavor. Patents are intended to offer some guarantee of a return on investment, but the patent system is also designed to balance the interests of inventors with those of the public. After a patent expires, a patented technology may be freely exploited by anyone. Drug switching refers to the practice of replacing a brand name drug with a generic drug. This practice is often used to reduce drug costs. JAMASOFT2017

Facilitating generic drug manufacturing: Bolar Exemptions Worldwide. To overcome this problem, many countries have put into place legal exemptions (or research exemptions) from infringement for certain acts relating to the development and submission of testing data to a regulatory agency. These exemptions are often referred to as “Bolar” exemption. JAMASOFT2017

In patent law, there is an exemption to the rights conferred by patents, which is especially relevant to drugs. JAMASOFT2017

Facilitating generic drug manufacturing: Bolar exemptions worldwide. Within Europe, there exists a defence to patent infringement commonly referred to as the “Bolar” exemption, which applies to acts legitimately undertaken for the regulatory approval of medicinal products. Many nations have put similar exemptions in place, but their nature and scope vary significantly from country to country. JAMASOFT2017

The Bolar exemption was a small part of a comprehensive reform of the current European Union pharmaceutical legislation proposed by the European Commission in July 2001. JAMASOFT2017

Authorisation of Medicinal Products and Switching of Medicine-Status. Prescription medicines are increasingly being switched to over-the-counter (OTC, nonprescription) status in the developed world, with the support of government policy. JAMASOFT2017

Thanks for your attention. JAMASOFT2017