Changes from plenary report to adopted text

Added(b) remote inspections, where justified;

Added(c) compliance control measures;

Added(d) the effective follow-up of the measures referred to in points (a), (b) and (c).

Added2. The competent authorities of the Member State concerned, and the Agency shall exchange information on the inspections referred to in paragraph 1, second subparagraph, points (a) and (b), that are planned or that have been conducted and shall cooperate in the coordination of such inspections.

Added3. The competent authority of the Member State shall ensure that the measures referred to in paragraph 1, second subparagraph, are carried out by the official representatives of the competent authority of the Member State:

Added(a) at an appropriate frequency based on risk, at the premises or on the activities of manufacturers of medicinal products, located in the Union or in third countries, including where appropriate at central or decentralised site(s), and at the premises or on the activities of wholesale distributors of medicinal products located in the Union;

Added(b) at an appropriate frequency based on risk, at the premises or on the activities of the manufacturers of active substances located in the Union or in third countries and at the premises or on the activities of importers, or distributors of active substances, located in the Union.

Added4. To determine the appropriate frequency based on risk referred to in paragraph 3, point (b), the competent authority of the Member State may:

Added(a) rely on inspection reports from trusted non-Union regulatory authorities;

Added(b) take into account whether the manufacturer of active substance is located in a third country included in the list referred to in Article 159(2).

Added5. Where the competent authority of the Member State considers it necessary, in particular where there are grounds for suspecting non-compliance with the rules of this Directive, including with the principles of good manufacturing practice and good distribution practices, referred to in Articles 160 and 161, or based on a risk assessment, it may have its official representatives carry out the measures referred to in paragraph 1, second subparagraph at the premises or on the activities of: [Am. 303]

Added(a) manufacturers or importers of medicinal products applying for a manufacturing import authorisation or wholesale distributors applying for a wholesale distribution authorisation;

Added(b) manufacturers of active substance applying for a registration or manufacturing sites applying for a registration as decentralised sites;

Added(c) marketing authorisation holders;

Added(d) distributors of medicinal products or manufacturers or distributors of active substances located in third countries; [Am. 304]

Added(e) manufacturers of excipients, functional excipients, starting materials or intermediate products located in its territory or in a third country;

Added(f) importers of excipients, functional excipients, starting materials or intermediate products located in its territory;

Added(g) persons brokering medicinal products located in its territory.

Added5a. The Agency shall draw up guidelines on the use of the Union database. [Am. 305]

Added6. The measures referred to in paragraph 1, second subparagraph, may also be carried out at the request of a competent authority of a Member State, the Commission or the Agency in the Union or in third countries or, where appropriate, by asking an Official Medicines Control Laboratory or a laboratory that Member State has designated for that purpose to carry out tests on samples.

Added7. Each Member State shall ensure that official representatives of its competent authorities are empowered and required to carry out one or more of the following activities:

Added(a) inspect the manufacturing or commercial establishments of manufacturers of medicinal products, of active substances or of excipients, and any laboratories employed by the manufacturing authorisation holder to carry out verifications and controls pursuant to Article 8;

Added(b) take samples during an inspection or request samples as part of the measures referred to in paragraph 1, second subparagraph, including any required essential testing material or reagent with a view to independent tests being carried out by an Official Medicines Control Laboratory or a laboratory that a Member States has designated for that purpose;

Added(c) inspect the premises, records, documents and pharmacovigilance system master file of the marketing authorisation holder or any undertaking employed by the marketing authorisation holder to perform the activities described in Chapter IX.

Added8. Inspections referred to in paragraph 1, second subparagraph, points (a) and (b), shall be carried out in accordance with the principles referred to in Article 190.

Added9. After every inspection carried out in accordance with paragraphs 3 and 5, the competent authority of the Member State concerned shall issue a report on the compliance of the manufacturing activities inspected with the good manufacturing practice and good distribution practices referred to in Articles 160 and 161, as applicable.

Added10. The competent authority of the Member State that had its official representatives carry out inspections in accordance with paragraphs 3 and 5, shall share its draft report with the inspected entity.

Added11. Before adopting the report, the competent authority of the Member State shall give the inspected entity the opportunity to submit comments.

Added12. Without prejudice to any arrangements that may have been concluded between the Union and third countries, a Member State, the Commission or the Agency may require a manufacturer of a medicinal product or of an active substance established in a third country to submit to an inspection as referred to in this Article.

Added13. Within 90 days of the conclusion of an inspection carried out in accordance with paragraphs 3 and 5 the competent authority of the Member State concerned shall issue to the inspected entity a certificate of compliance of good manufacturing practice or good distribution practices if the outcome of that inspection shows that the inspected entity complies with the principles of good manufacturing practice or good distribution practices referred to in Articles 160 and 161.

Added14. If the outcome of the inspection carried out in accordance with paragraph 3, 4 and 5 shows that the inspected entity does not comply with the principles of good manufacturing practice or good distribution practices as referred to in Articles 160 and 161, the competent authority of the Member State concerned shall issue a statement of non-compliance.

Added15. The competent authority of the Member State shall enter the certificates of good manufacturing practice or good distribution practices in the relevant Union database managed by the Agency on behalf of the Union. Pursuant to Article 157, the competent authority of the Member States shall also enter information in that database regarding the registration of importers, manufacturers and distributors of active substances and decentralised sites performing decentralised manufacturing activities, including their respective database link to the manufacturing authorisation of the central site.

Added16. If the outcome of the inspection carried out in accordance with paragraph 5 is that the inspected entity does not comply with the legal requirements or the principles of good manufacturing practice or good distribution practices as referred to in Articles 160 and 161 the information shall be entered in the Union database as referred to in paragraph 15.

Added17. If the outcome of the activity carried out in accordance with paragraph 7, point (c), is that the marketing authorisation holder does not comply with the pharmacovigilance system as described in the pharmacovigilance system master file and with Chapter IX, the competent authority of the Member State concerned shall bring the deficiencies to the attention of the marketing authorisation holder and give the marketing authorisation holder the opportunity to submit comments.

AddedIn such case the Member State concerned shall inform the other Member States, the Agency and the Commission accordingly.

AddedWhere appropriate, the Member State concerned shall take the necessary measures to ensure that a marketing authorisation holder is subject to effective, proportionate and dissuasive penalties as laid down in Article 206.

AddedArticle 189 Cooperation on inspections

Added1. Upon request by one or more competent authorities, inspections referred to in Article 188, paragraphs 3 and 5, may be carried out by official representatives from more than one Member State, together with the inspectors of the Agency in accordance with Article 52(2), point (a) of [revised Regulation (EC) No 726/2004] (‘the joint inspection’).

AddedThe competent authority of the Member State receiving a request for a joint inspection, shall make all reasonable efforts to accept such a request, and coordinate and support that joint inspection, where:

Added(a) it is demonstrated, or there are reasonable ground for suspecting, that the activities carried out on the territory of the Member State receiving the request pose a risk to the safety and quality in the Member State of the competent authority requesting the joint inspection;

Added(b) competent authorities of the Member State requesting the joint inspection require specialist technical expertise available in the Member State receiving the joint inspection request;

Added(c) the competent authority of the Member State receiving the request agrees that there are other reasonable grounds such as training of inspectors, sharing of good practice, for conducting a joint inspection.

Added2. The competent authorities participating in a joint inspection shall conclude an agreement prior to the inspection that defines at least the following:

Added(a) the scope and objective of the joint inspection;

Added(b) the roles of the participating inspectors during and following the inspection, including the designation of an authority leading the inspection;

Added(c) the powers and responsibilities of each of the competent authorities.

Added3. The competent authorities participating in the joint inspection shall commit themselves in that agreement to jointly accept the results of the inspection.

Added4. Where the joint inspection is conducted in one of the Member States, the competent authority leading the joint inspection shall ensure that the joint inspection is carried out in accordance with the national legislation of the Member State in which the joint inspection takes place.

Added5. Member States may set up joint inspection programmes to facilitate routine joint inspections. Member States may operate such programmes under a agreement as referred to in paragraphs 2 and 3.

Added6. A competent authority of a Member State may request another competent authority to take over one of its inspections referred to in Article 188, paragraphs 3 and 5.

Added7. The other competent authority of the Member State shall communicate to the requesting competent authority whether it accepts the request to conduct the inspection within 10 days. Where it accepts, it shall be responsible as the competent authority to carry out the inspections pursuant to this Section.

Added8. For the purposes of paragraph 6, and when the request is agreed, the requesting competent authority shall, in a timely manner, submit the relevant information necessary to conduct the inspection to the competent authority of the Member State that accepted the request.

AddedArticle 190 Inspection guidelines

Added1. The Commission may adopt implementing acts to lay down the principles applicable to:

Added(a) the system of supervision referred to in Article 188(1);

Added(b) the joint inspections referred to in Article 189(1);

Added(c) the exchange of information and cooperation in the coordination of inspections in the system of supervision between the Member States and the Agency; and

Added(d) trusted non-Union regulatory authorities.

AddedThe implementing acts referred to in the first subparagraph shall be adopted in accordance with the procedure referred to in Article 214(2).

Added2. Member States shall, in cooperation with the Agency, establish the form and content of the manufacturing authorisation referred to in Article 142(1) and of the wholesale distribution authorisation referred to in Article 163(1), of the report referred to in Article 188, of the certificates of good manufacturing practice and of the certificates of good distribution practices referred to in Article 188(13).