What changed between the plenary report and the adopted text

Removed:EXPLANATORY STATEMENT

Added:(69) ‘brokering of medicinal products’ means all activities in relation to the sale or purchase of medicinal products, except for wholesale distribution, that do not include physical handling and that consist of negotiating independently and on behalf of another legal or natural person;

Removed:The Union general pharmaceutical legislation was established in 1965 with the dual objective of safeguarding public health and harmonising the internal market for medicines. The latest proposal of the European Commission for revision of this legislation includes a new Directive and a new Regulation to replace pharmaceutical legislation currently in force, with the overall objectives of promoting innovation, ensuring access to innovative and established medicines for patients, and creating a balanced and competitive system that keeps medicines affordable for health systems while rewarding innovation. Of the ‘Pharmaceutical Package’, this Directive contains all the requirements for authorisation, monitoring, labelling and regulatory protection, placing on the market and other regulatory procedures for all medicines authorised at EU and national level.

Added:(70) ‘public service obligation’ means to guaranteeensure permanently an adequate range of medicinal products to meet the requirements of a specific geographical area and to deliver the supplies requested within a very short time over the whole of the area in question. [Am. 110]

Removed:The Rapporteur supports the objectives of the European Commission’s proposal and finds that a revision of current Union general pharmaceutical legislation comes at the right time: Europe is increasingly falling behind other regions in pharmaceutical research and development investments, novel technologies challenge the existing legislative framework, and the COVID-19 pandemic demonstrated the need for timely and equitable access to medicines.

Added:2. The Commission is empowered to adopt delegated acts in accordance with Article 215 to amend the definitions in paragraph 1, points (2) to (6), (8), (14), (16) to (3128), and (30) in the light of technical and scientific progress and taking into account definitions agreed at Union and international level without extending the scope of the definitions. [Am. 111]

Removed:Incentivising Innovation

Added:Chapter II Application requirements for national and centralised marketing authorisations

Removed:The Rapporteur believes that increasing the number of innovative medicinal products available to Europeans is of crucial benefit to patients and society. In this regard, the Directive must present a framework for rewarding innovation which is attractive to the global pharmaceutical industry, including the wider research-based life-science environment.

Added:Section 1 General provisions

Removed:Making Europe competitive is an objective which requires a multifactorial solution. However, among the key factors, which is within the scope of this Directive, is the system of incentives and namely the regulatory data protection. Regulatory data protection affects companies’ decisions to invest in innovation and to bring scientific innovation to launch on the Union market. In this regard, the Rapporteur finds that the level of regulatory data protection offered on the Union market should be competitive with what is being offered in other markets. Furthermore, there should be certainty and long-term predictability regarding the level of regulatory data protection to be expected, which means that a significant amount of the total regulatory data protection should remain within the ‘baseline’.

Added:Article 5 Marketing authorisations

Removed:The Rapporteur agrees with the European Commission’s proposal that further incentives on top of an attractive baseline of regulatory data protection may help steer innovation and finds that a definition of unmet medical need should be considered from both the individual patient and societal perspectives. That is, innovation for unmet medical need should be sufficiently incentivised, while the definitions applied for deciding which medicinal products address an unmet medical need should consider the patient perspective centrally. In this regard, the Rapporteur finds that the concept of ‘quality of life’ of patients should be considered.

Added:1. A medicinal product shall be placed on the market of a Member State only when a marketing authorisation has been granted by the competent authorities of a Member State in accordance with Chapter III (‘national marketing authorisation’) or a marketing authorisation has been granted in accordance with [revised Regulation (EC) No 726/2004] (‘centralised marketing authorisation’).

Removed:Outside of regulatory data protection, the Rapporteur also proposes to increase the reward for completion of a paediatric investigation plan where this is completed for a different disease than the one for which a medicinal product is intended in the adult population.

Added:2. When an initial marketing authorisation has been granted in accordance with paragraph 1, any development concerning the medicinal product covered by the authorisation such as additional therapeutic indication, strengths, pharmaceutical forms, administration routes, presentations, as well as any variations of the marketing authorisation shall also be granted an authorisation in accordance with paragraph 1 or be included in the initial marketing authorisation. All those marketing authorisations shall be considered as belonging to the same global marketing authorisation, in particular for the purpose of the marketing authorisations applications under Articles 9 to 12, including as regards the expiry of the regulatory data protection period for applications using a reference medicinal product.

Removed:Access to Medicines

Added:Article 6 General requirements for marketing authorisation applications

Removed:The European Commission has proposed an incentive which will grant a prolongation of data protection if a medicinal product is supplied in accordance with the needs of the Member States concerned within two years from the marketing authorisation (or within three years in the case of SMEs, not-for-profit entities or companies with limited experience in the EU system). The Rapporteur opposes this measure, by which the European Commission intends to promote access to medicinal products. Firstly, because the release and continuous supply of medicinal products is not only within the control of the marketing authorisation holder but also relies on the Member State competent authorities. Thus, it would be disproportionate to place all responsibility, and direct consequences, for a failure to launch only on the marketing authorisation holder. Secondly, linking the failure to comply with the conditionality of supply in every Member State to losing out on regulatory data protection will be to the detriment of innovation, as described above. Finally, the Rapporteur is concerned about how this measure would work in relation to orphan medicinal products and ATMPs.

Added:1. In order to obtain a marketing authorisation, an electronic marketing authorisation application shall be submitted to the competent authority concerned in a common format. The Agency shall make available such format after consultation with the Member States.

Removed:Rather, the Rapporteur proposes to place an obligation on marketing authorisation holders to submit in every Member State, which requested them to do so, an application for pricing and reimbursement. In case of non-compliance with the obligation, a proportional financial penalty shall be applied by affected Member States. This can promote access to medicinal products across Europe, while ensure predictability in the expectations, as well as in the possible penalties, of marketing authorisation holders. Marketing authorisation holders of orphan medicinal products and ATMPs shall be subject to an adapted obligation, and in special cases the European Commission may exempt specific medicinal products. To further the processes surrounding the obligation, the European Commission shall set up an “EU Access to Medicines Notification System”.

Added:2. The marketing authorisation application shall include the particulars and documentation listed in Annex I, submitted in accordance with Annex II.

Removed:Environmental Health

Added:2a. A marketing authorisation may be granted for a medicinal product on the basis of an active substance master file, an additional quality master file or a platform technology master file where such a file exists and is referred to in the application. [Am. 112]

Removed:The Rapporteur welcomes the initiative of the European Commission to strengthen measures related to the environmental impact of medicines, and, by extension, the impact on human health of negative environmental impacts. However, these should be proportionate and not unjustly have a negative effect on patients.

Added:3. The documents and information concerning the results of the pharmaceutical and non-clinical tests and the clinical studies referred to in Annex I shall be accompanied by detailed summaries in accordance with Article 7 and supportive raw data.

Removed:Notably, the Rapporteur finds that in case of serious risks to the environment a marketing authorisation may be suspended or varied, but should only be revoked in cases where those risks clearly outweigh the loss of positive therapeutic effect of the medicine. The Rapporteur also asks the Commission to ensure that the proper guidelines for conducting environmental risk assessments for antimicrobials other than antibiotics are in place before obligations in this regard shall apply. When specifying technical details for the environmental risk assessments, all relevant stakeholders shall be consulted. As regards medicines for which a prescription is needed, the Rapporteur wishes to ensure continued patient access to antimicrobials not for systemic use.

Added:4. The risk management system referred to in Annex I shall be proportionate to the identified risks and the potential risks to human health or the environment of the medicinal product, and the need for post-authorisation safety data. [Am. 113]

Removed:The Rapporteur suggests to place extended obligations on the Member States with regard to the appropriate collection and management of unused or expired medicines. In this regard, Member States are asked to draw up national plans, including measures designed to inform the public and healthcare professionals about environmental risks in regard to incorrect disposal of medicines and increase its rate of correct disposal of medicines.

Added:5. The marketing authorisation application for a medicinal product that is not authorised in the Union at the time of entry into force of this Directive and for new therapeutic indications, including paediatric indications, new pharmaceutical forms, new strengths and new routes of administration of authorised medicinal products which are protected either by a supplementary protection certificate under [Regulation (EC) No 469/2009 - OP please replace reference by new instrument when adopted], or by a patent which qualifies for the granting of the supplementary protection certificate, shall include one of the following:

Removed:Patient-centred Information

Added:(a) the results of all studies performed and details of all information collected in compliance with an agreed paediatric investigation plan;

Removed:The Rapporteur places emphasis on the importance of properly ensuring accurate information to patients about the medicines they consume. The first objective of package leaflets shall be to meet the needs of patients. Whether the leaflet is in electronic or in paper format, its content must be legible, clear and easy to use. The Rapporteur proposes that the package leaflet shall contain a ‘key information section’ to support this objective.

Added:(b) a decision of the Agency granting a product-specific waiver pursuant to Article 75(1) of [revised Regulation (EC) No 726/2004];

Removed:The addition by the European Commission of electronic information can, in this regard, benefit some patients. However, where no other position has been taken, the information should be available in the form of both paper leaflets and electronic product information. The decision to make information available only electronically shall lay with each Member State, and in this case, patients shall be made aware of their right to a printed copy. However, where the medicinal product is not intended to be delivered directly to, and administered by, the patient the Commission may take the decision to make only the electronic product information mandatory.

Added:(c) a decision of the Agency granting a class waiver pursuant to Article 75(2) of [revised Regulation (EC) No 726/2004];

Removed:Awareness cards shall be available in paper format, or in both paper format and electronically, to support that this information is duly received by patients. The Rapporteur supports the proposal of the European Commission that Member States may make exemptions to the language requirements of labelling, however, patients should, in this case, still be able to request a copy in the official language of their Member State.

Added:(d) a decision of the Agency granting a deferral pursuant to Article 81 of [revised Regulation (EC) No 726/2004];

Added:(e) a decision of the Agency taken in consultation with the Commission pursuant to Article 83 of [revised Regulation (EC) No 726/2004] to temporarily derogate from the provision referred to in points (a) to (d) above in case of health emergencies.

Added:The documents submitted under points (a) to (d) shall, cumulatively, cover all subsets of the paediatric population.

Added:In the absence of a paediatric investigation plan in accordance with the first subparagraph, point (a), or where in this regard a comparative study has not been carried out, a justification shall be submitted and where relevant also evidence shall be obtained from post-marketing long-term studies. [Am. 114]

Added:6. The provisions of paragraph 5 shall not apply to medicinal products authorised under Articles 9, 11, 13, Articles 125 to 141 and medicinal products authorised under Articles 10 and 12 which are not protected either by a supplementary protection certificate under [Regulation (EC) No 469/2009 - OP please replace reference by new instrument when adopted], or by a patent which qualifies for the granting of the supplementary protection certificate.

Added:7. The marketing authorisation applicant shall demonstrate that the principle of replacement, reduction and refinement of animal testing for scientific purposes has been applied in compliance with Directive 2010/63/EU with regard to any animal study conducted in support of the application.

Added:The marketing authorisation applicant shall not carry out animal testing in case scientifically satisfactory non-animal testing methods are available. Where scientifically satisfactory non-animal testing methods are not available, applicants that use animal testing shall ensure that the principle of replacement, reduction and refinement of animal testing for scientific purposes has been applied in compliance with Directive 2010/63/EU with regard to any animal study conducted for the purpose of supporting the application. [Am. 115]

Added:Article 7 Expert verification

Added:1. The marketing authorisation applicant shall ensure that the detailed summaries referred to in Article 6(3) have been drawn up and signed by experts with the necessary technical or professional qualifications before they are submitted to the competent authorities. The technical or professional qualifications of the experts shall be set out in a brief curriculum vitae.

Added:2. The experts referred to in paragraph 1 shall justify any use made of scientific literature under Article 13 in accordance with the requirements set out in Annex II.

Added:Article 8 Medicinal products manufactured outside the Union

Added:Member States shall take all appropriate measures to ensure that:

Added:(a) the competent authorities of the Member States verify that manufacturers and importers of medicinal products coming from third countries are able to carry out manufacture in compliance with the particulars supplied pursuant to Annex I, or to carry out controls according to the methods described in the particulars accompanying the application in accordance with Annex I;

Added:(b) the competent authorities of the Member States may allow manufacturers and importers of medicinal products coming from third countries, in justifiable cases, to have certain stages of manufacture or certain of the controls referred to in point (a) carried out by third parties; in such cases, the verifications by the competent authorities of the Member States shall also be made in the establishment designated.

Added:Section 2 Specific requirements for abridged applications for marketing authorisation

Added:Article 9 Applications concerning generic medicinal products

Added:1. By way of derogation from Article 6(2), the applicant for a marketing authorisation for a generic medicinal product shall not be required to provide to the competent authorities the results of non-clinical tests and of clinical studies if equivalence of the generic medicinal product with the reference medicinal product is demonstrated.

Added:2. For the purpose of demonstrating the equivalence as referred to in paragraph 1, the applicant shall submit to the competent authorities equivalence studies, or a justification as to why such studies were not performed, and demonstrate that the generic medicinal product meets the relevant criteria set out in the appropriate detailed guidelines.

Added:3. Paragraph 1 shall also apply if the reference medicinal product has not been authorised in the Member State in which the application for the generic medicinal product is submitted. In this case, the applicant shall indicate in the application the name of the Member State in which the reference medicinal product is or has been authorised. At the request of the competent authority of the Member State in which the application is submitted, the competent authority of the other Member State shall transmit within a period of one month a confirmation that the reference medicinal product is or has been authorised together with the full composition of the reference medicinal product and if necessary, any other relevant documentation.

Added:The various immediate-release oral pharmaceutical forms shall be considered to be the same pharmaceutical form.

Added:4. The different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be the same active substance, unless they differ significantly in properties with regard to safety or efficacy. In those cases, the applicant shall submit additional information to demonstrate that the different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance do not differ significantly in respect of those properties.

Added:5. Where there is a significant difference in properties as referred to in paragraph 4, the applicant shall submit additional information in order to prove the safety or efficacy of the different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of the authorised active substance of the reference medicinal product in an application under Article 10.

Added:Article 10 Applications concerning hybrid medicinal products