What changed between the plenary report and the adopted text

Added:(a) have at their disposal the services of staff who comply with the legal requirements existing in the Member State both as regards manufacture and controls;

Added:(b) dispose of the medicinal products that have been granted a marketing authorisation only in accordance with the legislation of the Member States;

Added:(c) give prior notice to the competent authority of the Member State of any changes they may wish to make to any of the particulars provided in accordance to Article 143;

Added:(d) allow the official representatives of the competent authority of the Member State access to their premises and, where sites carry out manufacturing or testing activities in connection with a central site in the decentralised site, to the premises of the central or the decentralised sites at any time;

Added:(e) enable the qualified persons referred to in Article 151 to carry out their duties, where appropriate also in decentralised sites, for example by placing at their disposal all the necessary resources;

Added:(f) comply, in any relevant site and at all times with the principles of good manufacturing practice for medicinal products;

Added:(g) use only active substances that have been manufactured in accordance with good manufacturing practice for active substances and distributed in accordance with good distribution practices for active substances;

Added:(h) inform the competent authority of the Member State and the marketing authorisation holder immediately if they obtain information that medicinal products that come under the scope of their manufacturing authorisation are, or are suspected of being, falsified irrespective of the way the medicinal products were distributed;

Added:(i) verify that the manufacturers, importers or distributors from whom they obtain active substances are registered with the competent authority of the Member State in which they are established; and

Added:(j) verify the authenticity and quality of the active substances and the excipients.

Added:(ja) use an appropriate wastewater treatment system; [Am. 276]

Added:(jb) comply with relevant risk mitigation measures identified in accordance with Article 22. [Am. 277]

Added:As regards the first subparagraph, point (c), the competent authority of the Member State shall, in any event, be immediately informed if the qualified person referred to in Articles 143(1), point (c), and 151 is replaced unexpectedly.

Added:For the purposes of points (f) and (g), manufacturing authorisation holders shall verify compliance, respectively, by the manufacturer or distributors of active substances with good manufacturing practice and good distribution practices by conducting audits at the manufacturing and distribution sites of the manufacturer and distributors of active substances. Manufacturing authorisation holders shall verify such compliance either by themselves or through an entity acting on their behalf under a contract.

Added:2. The manufacturing authorisation holder shall ensure that the excipients are suitable for use in medicinal products by ascertaining the appropriate good manufacturing practice on the basis of a formalised risk assessment.

Added:3. The manufacturing authorisation holder shall ensure that the appropriate good manufacturing practice ascertained in accordance with paragraph 2, is applied. The manufacturing authorisation holder shall document the measures taken in accordance with paragraphs 1 and 2.

Added:Article 148 Registration and listing process of decentralised sites

Added:1. The manufacturing authorisation holder of the central site shall register all of its decentralised sites in accordance with the provisions of this Article.

Added:2. The manufacturing authorisation holder of the central site shall request the competent authority of the Member State in which the decentralised site is established, to register the decentralised site.

Added:3. The marketing authorisation holder may commence the activity in the decentralised site in connection with the central site only when the decentralised site is registered in the Union database referred to in Article 188(15) and the link is made in the database with the authorisation of the corresponding central site by the competent authority of the Member state where the decentralised site is located.

Added:4. The competent authority of the Member State in which the decentralised site is established, is responsible, in accordance with Article 188, for the supervision of the manufacturing and testing activities carried out in the decentralised site.

Added:5. For the purpose of paragraph 2 the manufacturing authorisation holder of the central site shall submit a registration form that shall include, at least, the following information:

Added:(a) name or corporate name and permanent address of the decentralised site and a proof of establishment in the Union;

Added:(b) the medicinal products that are subject to manufacturing or testing steps in the decentralised site, including the manufacturing or testing activities to be performed for those medicinal products;

Added:(c) particulars regarding the premises of the decentralised site and the technical equipment to carry out the relevant activities;

Added:(d) the reference to the manufacturing authorisation of the central site;

Added:(e) the written confirmation referred to in Article 144(2), second subparagraph, that the manufacturer of the medicinal product has verified compliance of the decentralised site with principles of good manufacturing practice referred to in Article 160 by conducting audits.

Added:6. The competent authority of the Member State supervising the decentralised site pursuant to paragraph 4 may decide to carry out an inspection as referred to in Article 188(1), first subparagraph, point (a). In such cases, that competent authority shall cooperate with the competent authority of the Member State responsible for the supervision of the central site.

Added:7. Following the registration of the decentralised site pursuant to paragraph 2, the manufacturing authorisation holder of the central site shall list the registered decentralised site in the manufacturing authorisation of the central site.

Added:8. The competent authority of the Member State supervising the decentralised site pursuant to paragraph 4 shall cooperate with the relevant authorities responsible for the supervision of the manufacturing or testing activities under other Union acts as regards the following:

Added:(a) the medicinal products that were manufactured in a decentralised site, the testing or manufacturing of which involves using raw material, medicinal products regulated under other relevant Union law, or medicinal products that are intended to be combined with medical devices;

Added:(b) where specific manufacturing or testing activities are applied to the medicinal products containing, consisting or derived from SoHO for which specific manufacturing or testing activities are applied within a decentralised site that is also authorised under [SoHO Regulation].

Added:9. Where relevant, competent authorities of the Member State supervising the central and decentralised sites mayshall liaise with the competent authority of the Member State responsible for the supervision of the marketing authorisation. [Am. 278]

Added:Article 149 Conditions related to the safety feature

Added:1. The safety features referred to in Annex IV shall not be removed or covered, either fully or partially, unless the following conditions are fulfilled:

Added:(a) the manufacturing authorisation holder verifies, prior to partly or fully removing or covering those safety features, that the medicinal product concerned is authentic and that it has not been tampered with;

Added:(b) the manufacturing authorisation holder complies with Annex IV by replacing those safety features with safety features that are equivalent as regards the possibility to verify the authenticity, identification and to provide evidence of tampering of the medicinal product. Such replacement shall be conducted without opening the immediate packaging.

Added:Safety features shall be considered equivalent if they:

Added:(i) comply with the requirements set out in the delegated acts adopted pursuant to Article 67(2); and

Added:(ii) are equally effective in enabling the verification of authenticity and identification of medicinal products and in providing evidence of tampering with medicinal products;

Added:(c) the replacement of the safety features is conducted in accordance with applicable good manufacturing practice for medicinal products; and

Added:(d) the replacement of the safety features is subject to supervision by the competent authority of the Member State.

Added:2. Manufacturing authorisation holders, including those performing the activities referred to in paragraph 1, shall be regarded as producers and therefore held liable for damages in the cases and under the conditions set forth in Directive 85/374/EEC.

Added:Article 150 Potentially falsified medicinal products

Added:1. By derogation from Article 1(2), and without prejudice to Chapter XII, Section 1, Member States shall take the necessary measures in order to prevent medicinal products that are introduced into the Union, but are not intended to be placed on the market in the Union, from entering into circulation if there are sufficient grounds to suspect that those products are falsified.

Added:2. Member States shall organise meetings involving patients’ and consumers’ organisations and, as necessary, Member States’ enforcement officers, in order to communicate public information about the actions undertaken in the area of prevention and enforcement to combat the falsification of medicinal products.

Added:3. In order to establish what the necessary measures referred to in paragraph 1 are the Commission is empowered to adopt delegated acts in accordance with Article 215, to supplement paragraph 1 by specifying the criteria to be considered and the verifications to be made when assessing the potential falsified character of medicinal products introduced into the Union but not intended to be placed on the market.

Added:Article 151 Availability of qualified person

Added:1. Member States shall take all appropriate measures to ensure that the manufacturing authorisation holder has permanently and continuously at their disposal the services of at least one qualified person residing and operating in the Union, in accordance with the conditions laid down in Article 152, responsible in particular for carrying out the duties specified in Article 153.

Added:2. A manufacturing authorisation holder who is a natural person and personally fulfils the conditions laid down in Annex III may assume the responsibility referred to in paragraph 1.

Added:3. Where the manufacturing authorisation is granted to a central site specified in the application pursuant to Article 144(3), the qualified person referred to in paragraph 1 shall also be responsible for carrying out the duties specified in Article 153(4) regarding the decentralised sites.

Added:Article 152 Qualification of qualified person

Added:1. Member States shall ensure that the qualified person referred to in Article 151 fulfils the conditions of qualification set out in Annex III.

Added:2. The manufacturing authorisation holder and the qualified person shall ensure that the practical experience acquired is appropriate to the types of products to be certified.

Added:3. The competent authority of the Member State may lay down appropriate administrative procedures to verify that a qualified person referred to in the paragraph 1 fulfils the conditions set out in Annex III.

Added:Article 153 Responsibilities of the qualified person

Added:1. Member States shall take all appropriate measures to ensure that the qualified person referred to in Article 151, without prejudice to their relationship with the manufacturing authorisation holder, are responsible, subject to the procedures referred to in Article 154, for securing:

Added:(a) in the case of medicinal products manufactured within the Member States concerned, that each production batch of medicinal products has been manufactured and checked in compliance with the laws in force in that Member State and in accordance with the requirements of the marketing authorisation;

Added:(b) in the case of medicinal products imported from third countries, irrespective of whether they have been manufactured in the Union that each production batch has undergone in a Member State a full qualitative analysis, a quantitative analysis of at least all the active substances and all the other tests or checks necessary to ensure the quality of the medicinal products in accordance with the requirements of the marketing authorisation.

Added:The qualified person referred to in Article 151 shall in the case of medicinal products intended to be placed on the Union market, ensure that the safety features referred to in Annex IV have been affixed on the packaging.