What changed between the plenary report and the adopted text

Added:Marketing authorisation holders shall ensure that those reports are accessible at a single point within the Union.

Added:By way of derogation from the first subparagraph, suspected adverse reactions occurring in the context of a clinical trial shall be recorded and reported in accordance with Regulation (EU) No 536/2014.

Added:2. Marketing authorisation holders shall not refuse to consider reports of suspected adverse reactions received electronically or by any other appropriate means from patients, carers or other relevant persons, such as family members, or healthcare professionals. [Am. 229]

Added:3. Marketing authorisation holders shall submit electronically to the database and data-processing network referred to in Article 101 of [revised Regulation (EC) No 726/2004] (‘Eudravigilance database’) information on all serious suspected adverse reactions that occur in the Union and in third countries within 15 days following the day on which the marketing authorisation holder concerned gained knowledge of the event.

Added:Marketing authorisation holders shall submit electronically to the Eudravigilance database information on all non-serious suspected adverse reactions that occur in the Union, within 90 days following the day on which the marketing authorisation holder concerned gained knowledge of the event.

Added:For medicinal products containing active substances referred to in the list of publications monitored by the Agency pursuant to Article 105 of [revised Regulation (EC) No 726/2004], marketing authorisation holders shall not be required to report to the Eudravigilance database the suspected adverse reactions recorded in the listed publications, but they shall monitor all other medical literature and report any suspected adverse reactions recorded therein.

Added:4. Marketing authorisation holders shall establish procedures in order to obtain accurate and verifiable data for the scientific evaluation of suspected adverse reaction reports. They shall also collect follow-up information on those reports and submit the updates to the Eudravigilance database.

Added:5. Marketing authorisation holders shall collaborate with the Agency and the competent authorities of the Member States in the detection of duplicates of suspected adverse reaction reports.

Added:6. This Article shall apply mutatis mutandis to undertakings supplying medicinal products used in accordance with Article 3, paragraphs 1 or 2.

Added:Article 106 Recording and reporting of suspected adverse reactions by Member States

Added:1. Each Member State shall record all suspected adverse reactions that occur in its territory and that are brought to its attention from healthcare professionals and patients. This shall include all authorised medicinal products and medicinal products used in accordance with Article 3, paragraphs 1 or 2. Member States shall involve patients and healthcare professionals, as appropriate, in the follow-up of any reports they receive in order to comply with Article 97(1), points (c) and (e), and shall seek to inform directly those stakeholders that reported a suspected adverse drug reaction on decisions taken in relation to the safety of the medicinal product. [Am. 230]

Added:Member States shall ensure that reports of such reactions may be submitted by means of the national medicines web-portals or by other means.

Added:2. For reports submitted by a marketing authorisation holder, Member States on whose territory the suspected adverse reaction occurred may involve the marketing authorisation holder in the follow-up of the reports.

Added:3. Member States shall collaborate with the Agency and the marketing authorisation holders in the detection of duplicates of suspected adverse reaction reports.

Added:4. Member States shall, within 15 days following the receipt of the reports of serious suspected adverse reactions referred to in paragraph 1, submit the reports electronically to the Eudravigilance database.

Added:Member States shall, within 90 days from the receipt of the reports referred to in paragraph 1, submit reports of non-serious suspected adverse reactions electronically to the Eudravigilance database.

Added:Marketing authorisation holders shall have access to the reports referred to in this paragraph through the Eudravigilance database.

Added:5. Member States shall ensure that reports of suspected adverse reactions arising from an error, including those associated with the use, administration, and dispensation of a medicinal product, by professionals, that are brought to their attention are made available to the Eudravigilance database and to any authorities, bodies, organisations or institutions, responsible for patient safety within that Member State concerned. They shall also ensure that the authorities responsible for medicinal products within that Member State are informed of any suspected adverse reactions brought to the attention of any other authority within that Member State. These reports shall be appropriately identified in the forms referred to in Article 102 of [revised Regulation (EC) No 726/2004]. [Am. 231]

Added:5a. Reports of adverse reactions arising from incorrect administration or dispensation of a medicinal product shall be available in the Eudravigilance database and shall be included in periodic safety update reports. Where relevant, Member States shall take corrective action to achieve high standards of medication safety in healthcare settings after consultation of healthcare professionals and other relevant stakeholders. [Am. 232]

Added:6. Unless there are justifiable grounds resulting from pharmacovigilance activities, Member States shall not impose any additional obligations on marketing authorisation holders for the reporting of suspected adverse reactions.

Added:Section 4 Periodic safety update reports

Added:Article 107 Periodic safety update reports

Added:1. Marketing authorisation holders shall submit to the Agency periodic safety update reports containing:

Added:(a) summaries of data relevant to the benefit-risk balance of the medicinal product, including results of all studies with a consideration of their potential impact on the marketing authorisation;

Added:(b) a scientific evaluation of the benefit-risk balance of the medicinal product;

Added:(c) all data relating to the volume of sales of the medicinal product and any data in possession of the marketing authorisation holder relating to the volume of prescriptions, including an estimate of the population exposed to the medicinal product.

Added:The data provided in accordance with the first subparagraph, point (c), shall differentiate between sales and volumes generated within the Union and those generated outside the Union.

Added:2. The evaluation referred to in paragraph 1, first subparagraph, point (b), shall be based on all available data, including data from clinical trials in unauthorised therapeutic indications and populations.

Added:The periodic safety update reports shall be submitted electronically.

Added:3. The Agency shall make available the reports referred to in paragraph 1 to the competent authorities of the Member States, the members of the Pharmacovigilance Risk Assessment Committee, the Committee for Medicinal Products for Human Use and the coordination group by means of the repository referred to in Article 103 of [revised Regulation (EC) No 726/2004].

Added:3a. The Agency or the national competent authorities, as appropriate, shall make publicly available the reports referred to in paragraph 1, points (a) and (b). [Am. 233]

Added:4. By way of derogation from paragraph 1, the marketing authorisation holders for medicinal products referred to in Articles 9, or 13, and the registration holders for medicinal products referred to in Articles 126 or 134(1), shall only be required to submit periodic safety update reports for such medicinal products to the competent authority in the following cases:

Added:(a) where such obligation has been laid down as a condition in the marketing authorisation in accordance with Articles 44 or 45; or

Added:(b) when requested by a competent authority on the basis of concerns relating to pharmacovigilance data or due to the lack of periodic safety update reports relating to an active substance after the marketing authorisation has been granted.

Added:The assessment reports of the periodic safety update reports referred to in the first subparagraph shall be communicated by the competent authority to the Pharmacovigilance Risk Assessment Committee, which shall consider whether there is a need for a single assessment report for all marketing authorisations for medicinal products containing the same active substance and which shall inform the coordination group or the Committee for Medicinal Products for Human Use accordingly, in order to apply the procedures laid down in Articles 108(4) and 110.

Added:Article 108 Frequency of periodic safety update reports

Added:1. The frequency with which the periodic safety update reports are to be submitted shall be specified in the marketing authorisation.

Added:The dates of submission according to the specified frequency shall be calculated from the date when then marketing authorisation was granted.

Added:2. Holders of marketing authorisations which have been granted before 21 July 2012, and for which the frequency and dates of submission of the periodic safety update reports are not laid down as a condition to the marketing authorisation, shall submit the periodic safety update reports in accordance with the second subparagraph until another frequency or other dates of submission of the reports are laid down in the marketing authorisation or determined in accordance with the paragraphs 4, 5 and 6.

Added:Periodic safety update reports shall be submitted to the competent authorities immediately upon request:

Added:(a) where a medicinal product has not yet been placed on the market, at least every six months following the marketing authorisation and until the placing on the market;

Added:(b) where a medicinal product has been placed on the market, at least every six months during the first two years following the initial placing on the market, once a year for the following two years and at three-yearly intervals thereafter.

Added:3. Paragraph 2 shall also apply to medicinal products that are authorised only in one Member State and for which paragraph 4 does not apply.

Added:4. Where medicinal products that are subject to different marketing authorisations contain the same active substance or the same combination of active substances, the frequency and dates of submission of the periodic safety update reports resulting from the application of the paragraphs 1 and 2 may be amended and harmonised to enable a single assessment to be made in the context of a periodic safety update report work-sharing procedure and to set a Union reference date from which the submission dates to be calculated.

Added:The harmonised frequency for the submission of the reports and the Union reference date may be determined, after consultation of the Pharmacovigilance Risk Assessment Committee, by one of the following:

Added:(a) the Committee for Medicinal Products for Human Use, where at least one of the marketing authorisations for the medicinal products containing the active substance concerned has been granted in accordance with the centralised procedure provided for in Article 3 of [revised Regulation (EC) No 726/2004];

Added:(b) the coordination group, in other cases than those referred to in point (a).

Added:The harmonised frequency for the submission of the reports determined pursuant to the first and second subparagraphs shall be made publicly available by the Agency. Marketing authorisation holders shall submit an application for a variation of the marketing authorisation accordingly.

Added:5. For the purposes of paragraph 4, the Union reference date for medicinal products containing the same active substance or the same combination of active substances shall be one of the following:

Added:(a) the date when the first marketing authorisation was granted in the Union for a medicinal product containing that active substance or that combination of active substances;

Added:(b) if the date referred to in point (a) cannot be ascertained, the earliest of the known dates of the marketing authorisations for a medicinal product containing that active substance or that combination of active substances.

Added:6. Marketing authorisation holders shall be allowed to submit requests to the Committee for Medicinal Products for Human Use or the coordination group, as appropriate, to determine Union reference dates or to change the frequency of submission of periodic safety update reports on one of the following grounds:

Added:(a) for reasons relating to public health;

Added:(b) in order to avoid a duplication of the assessment;

Added:(c) in order to achieve international harmonisation.

Added:Such requests shall be submitted in writing and shall be duly justified. The Committee for Medicinal Products for Human Use or the coordination group shall, following the consultation with the Pharmacovigilance Risk Assessment Committee, either approve or deny such requests. Any change in the dates or the frequency of submission of periodic safety update reports shall be made publicly available by the Agency. The marketing authorisation holders shall submit an application for a variation of the marketing authorisation accordingly.

Added:7. The Agency shall make public a list of Union reference dates and frequency of submission of periodic safety update reports by means of the European medicines web-portal.

Added:Any change to the dates of submission and frequency of periodic safety update reports specified in the marketing authorisation as a result of the application of the paragraphs 4, 5 and 6 shall take effect four months after the date of the publication referred to in the first subparagraph.

Added:Article 109 Assessment of periodic safety update reports

Added:The competent authorities of the Member State shall assess periodic safety update reports to determine whether there are new risks or whether risks have changed or whether there are changes to the benefit-risk balance of medicinal products.