Changes from plenary report to adopted text

AddedThe Agency may, at the request of a Member State, the Commission, or on its own initiative and on the basis of all available evidence, including any additional evidence that may be submitted by the marketing authorisation holders for the medicinal products concerned, make a scientific evaluation of the benefit-risk of the use of a medicinal product with a new therapeutic indication that concerns an unmet medical need. [Am. 169]

AddedThe opinion of the Agency shall be made publicly available and the competent authorities of the Member States and the marketing authorisation holder shall be informed. [Am. 170]

Added2. In cases where the opinion is favourable, marketing authorisation holders of the medicinal products concerned shall submit a variation to update the product information with the new therapeutic indication.

Added3. Article 81(2), point (c) of [revised Directive 2001/83/EC] shall not apply for variations under this Article. [Am. 171]

AddedArticle 49 Transfer of marketing authorisation

Added1. A marketing authorisation may be transferred to a new marketing authorisation holder. Such a transfer shall not be considered to be a variation. The transfer shall be subject to prior approval by the Commission, by means of implementing acts, following the submission of an application for the transfer to the Agency.

Added2. The Commission is empowered to adopt delegated acts in accordance with Article 175 to supplement this Regulation by establishing procedures for the examination of applications to the Agency for the transfer of marketing authorisations.

AddedArticle 50 Supervisory authority

Added1. In the case of medicinal products manufactured within the Union, the supervisory authorities for manufacturing shall be the competent authorities of the Member State or Member States which granted the manufacturing authorisation referred to in Article 142(1) of [revised Directive 2001/83/EC] in respect of the medicinal product concerned.

Added2. In the case of medicinal products imported from third countries, the supervisory authorities for imports shall be the competent authorities of the Member State or Member States that granted the authorisation referred to in Article 142(3) of [revised Directive 2001/83/EC] to the importer, unless appropriate agreements have been made between the Union and the exporting country to ensure that those controls are carried out in the exporting country and that the manufacturer applies standards of good manufacturing practice at least equivalent to those laid down by the Union.

AddedA Member State may request assistance from another Member State or from the Agency.

Added3. The supervisory authority for pharmacovigilance shall be the competent authority of the Member State in which the pharmacovigilance system master file is located.

AddedArticle 51 Responsibilities of the supervisory authorities

Added1. The supervisory authorities for manufacturing and imports shall be responsible for verifying on behalf of the Union that the marketing authorisation holder for the medicinal product or the manufacturer or importer established within the Union satisfies the requirements concerning manufacturing and imports laid down in Chapters XI and XV of [revised Directive 2001/83/EC].

AddedWhen carrying out the verification referred to in the first subparagraph, the supervisory authorities may request to be accompanied by a rapporteur or expert appointed by the Committee for Medicinal Products for Human Use or by an inspector of the Agency.

AddedThe supervisory authorities for pharmacovigilance shall be responsible for verifying on behalf of the Union that the marketing authorisation holder for the medicinal product satisfies the pharmacovigilance requirements laid down in Chapters IX and XV of [revised Directive 2001/83/EC].

AddedThe supervisory authorities for pharmacovigilance may, if necessary, conduct pre-authorisation inspections to verify the accuracy and successful implementation of the pharmacovigilance system as it has been described by the applicant in support of their application.

Added2. Where, in accordance with Article 202 of [revised Directive 2001/83/EC], the Commission is informed of serious differences of opinion between Member States as to whether the marketing authorisation holder for the medicinal product for human use or a manufacturer or importer established within the Union satisfies the requirements referred to in paragraph 1, the Commission may, after consultation with the Member States concerned, request an inspector from the supervisory authority to undertake a new inspection of the marketing authorisation holder, the manufacturer or the importer.

AddedThe inspector in question shall be accompanied by two inspectors from Member States which are not party to the dispute or by two experts nominated by the Committee for Medicinal Products for Human Use.

Added3. Taking into account any agreements which may have been concluded between the Union and third countries in accordance with Article 50, the Commission may, following a reasoned request from a Member State or from the Committee for Medicinal Products for Human Use, or on its own initiative, require a manufacturer established in a third country to submit to an inspection.

AddedThe inspection shall be undertaken by inspectors from the Member States who possess the appropriate qualifications. They may request to be accompanied by a rapporteur or expert appointed by the Committee for Medicinal Products for Human Use or by an inspector of the Agency. The report of the inspectors shall be made available electronically to the Commission, the Member States and the Agency.

AddedArticle 52 Inspection capacity of the Agency

Added1. When an inspection, included in the system of supervision referred to in Article 188(1), point (a) of [revised Directive 2001/83/EC] is requested, as referred to in Article 11(2), for a site located in a third country, the supervisory authority for this site may request the Agency to participate in the inspection or to carry out the inspection.

Added2. The Agency, following a request in accordance with paragraph 1, may decide either of the following:

Added(a) to lend its assistance by participating in a joint inspection with the supervisory authority of the site to assess compliance with good manufacturing practice (GMP) as well as any practices relating to environmental and worker safety. In that case the supervisory authority leads the inspection and the follow up thereof. After completion of the inspection, the supervisory authority grants the relevant good manufacturing practice (GMP)GMP certificate and enters the certificate in the Union database; or [Am. 172]

Added(b) to carry out the inspection and the follow up thereof on behalf of the supervisory authority. After completion of the inspection, the Agency grants the relevant GMP certificate and enters the certificate in the Union database referred to in Article 188(15) of [revised Directive 2001/83/EC].

AddedWhere the Agency decides to carry out the inspection, the Agency may request other Member States to participate in the inspection. To any such request, the provisions on joint inspections of Article 189 of [revised Directive 2001/83/EC] shall apply. In case the Agency carries out the inspection in form of a joint inspection, the Agency leads the inspection.

AddedThe Agency may also request to be accompanied by a rapporteur or expert appointed by the Committee for Medicinal Products for Human Use.

AddedWhere a follow-up inspection is required in view of a non-compliance GMP certificate issued by the Agency, the supervisory authority of the site will be in charge of its performance; the procedure of paragraph 2 shall apply if the supervisory authority for this site requests the Agency to participate in the follow up inspection or to take over the performance of the inspection.

Added3. The Agency shall take into account the criteria set out in Annex III when taking its decision in accordance with paragraph 2.

Added4. Article 188, paragraph 6, and paragraphs 8 to 17 of [revised Directive 2001/83/EC] shall apply to the inspections referred to in paragraph 2.

AddedThe Agency’s inspectors shall have the same powers conferred on official representatives of the competent authority pursuant to these provisions.

Added5. Following a request by a Member State, the inspectors of the Agency may provide support to such Member State when it performs inspections referred to in Article 78 of Regulation (EU) 536/2014. The Agency shall take a decision whether to carry out itself such inspection based on the criteria set out in Annex III.

Added6. The Agency shall ensure that

Added(a) appropriate resources are made available for the performance of inspection tasks in accordance with the paragraphs 2 and 5;

Added(b) the inspectors of the Agency possess expertise, technical knowledge, and formal qualifications equivalent to those of the national inspectors as detailed in the compilation, published by the Commission, on Union procedures on inspections and exchange of information.

Added(c) it participates as an inspectorate in the Joint Audit Programme and be subjected to periodic audits.

AddedArticle 53 International Inspections

Added1. The Agency shall in consultation with the Commission, coordinate a structured cooperation on inspections in third countries between Member States, and as relevant the European Directorate for the Quality of Medicines and Healthcare of the Council of Europe, the World Health Organisation and trusted international authorities, by means of international inspection programmes.

Added2. In cooperation with the Agency, the Commission mayshall adopt detailed guidelines laying down the principles applicable to those international inspection programmes. The guidelines shall include rules on impartially, independence and conflict of interest of inspectors. [Am. 173]

AddedArticle 54 Joint Audit Programme

Added1. The inspection working group referred to in Article 142, point (k), shall ensure the following:

Added(a) establish and develop the joint audit programme (‘JAP’) and supervise it;

Added(b) monitor any measure taken by the Member State pursuant and limited to paragraph 4;

Added(c) ensure cooperation with relevant international and Union level bodies to facilitate the work of the joint audit programme.

AddedFor the purposes of the first subparagraph, the inspection working group may establish an operational subgroup.

Added2. For the purposes of paragraph 1, point (a), each Member State shall:

Added(a) provide trained auditors;

Added(b) accept that the competent authority in charge of the implementation of good manufacturing and good distribution practice and related surveillance and enforcement activities applicable to medicinal products and active substances are audited, regularly and where appropriate, according to the joint audit programme.

Added3. The joint audit programme shall be considered an integral part of the quality system of the inspectorates referred to in Article 3(3) of Commission Directive (EU) 2017/1572 and ensure that adequate and equivalent quality standards are maintained within the Union network of national competent authorities.

Added4. Under the joint audit programme, the auditors shall issue an audit report after each audit. The audit report shall include, where relevant, appropriate recommendations on measures that the Member State concerned shall consider to take to ensure that its relevant quality system and its enforcement activities are consistent with Union quality standards.

AddedAt the request of the Member State, the Commission or the Agency may support that Member State in taking the appropriate measures pursuant to the first subparagraph.

Added5. For the purposes of paragraph 4, the Agency shall:

Added(a) ensure the quality and consistency of the joint audit programme’s audit reports;

Added(b) establish the criteria for the provision of the joint audit programme’s recommendations.

Added6. The compilation of Union procedures on inspections and exchange of information referred to in Article 3(1) of Directive 2017/1572 shall be updated by the Agency to cover rules applicable to the functioning, structure, and tasks of the joint audit programme.

Added7. The Union shall provide the financing for activities that support the work of the joint audit programme.

AddedArticle 55 Referral procedure

Added1. Where the supervisory authorities or the competent authorities of any other Member State are of the opinion that the manufacturer or importer established within the Union territory is no longer fulfilling the obligations laid down in Chapter XI of [revised Directive 2001/83/EC], they shall without undue delay inform the Agency and the Commission, stating their reasons in detail and indicating the course of action proposed.

AddedSimilarly, where a Member State or the Commission considers that one of the measures envisaged in Chapters IX, XIV and XV of [revised Directive 2001/83/EC] is to be applied in respect of the medicinal product concerned or where the Committee for Medicinal Products for Human Use has delivered an opinion to that effect, they shall without undue delay inform each other, as well as the Committee for Medicinal Products of Human Use, stating their reasons in detail and indicating the course of action proposed.