TITLE IX

PHARMACOVIGILANCE
CHAPTER 4

Supervision of post-authorisation safety studies
Article 107m
1
This Chapter applies to non-interventional post-authorisation safety studies which are initiated, managed or financed by the marketing authorisation holder voluntarily or pursuant to obligations imposed in accordance with Articles 21a or 22a, and which involve the collection of safety data from patients or healthcare professionals.
2
This Chapter is without prejudice to national and Union requirements for ensuring the well-being and rights of participants in non-interventional post-authorisation safety studies.
3
The studies shall not be performed where the act of conducting the study promotes the use of a medicinal product.
4
Payments to healthcare professionals for participating in non-interventional post-authorisation safety studies shall be restricted to the compensation for time and expenses incurred.
5
The national competent authority may require the marketing authorisation holder to submit the protocol and the progress reports to the competent authorities of the Member States in which the study is conducted.
6
The marketing authorisation holder shall send the final report to the competent authorities of the Member States in which the study was conducted within 12 months of the end of data collection.
7
While a study is being conducted, the marketing authorisation holder shall monitor the data generated and consider its implications for the risk-benefit balance of the medicinal product concerned.
Any new information which might influence the evaluation of the risk-benefit balance of the medicinal product shall be communicated to the competent authorities of the Member State in which the medicinal product has been authorised in accordance with Article 23.
The obligation laid down in the second subparagraph is without prejudice to the information on the results of studies that the marketing authorisation holder shall make available by means of the periodic safety update reports as laid down in Article 107b.
8
Articles 107n to 107q shall apply exclusively to studies referred to in paragraph 1 which are conducted pursuant to an obligation imposed in accordance with Articles 21a or 22a.
Article 107n
1
Before a study is conducted, the marketing authorisation holder shall submit a draft protocol to the Pharmacovigilance Risk Assessment Committee, except for studies to be conducted in only one Member State that requests the study according to Article 22a. For such studies, the marketing authorisation holder shall submit a draft protocol to the national competent authority of the Member State in which the study is conducted.
2
Within 60 days of the submission of the draft protocol the national competent authority or the Pharmacovigilance Risk Assessment Committee, as appropriate, shall issue:
a
a letter endorsing the draft protocol;
b
a letter of objection, which shall set out in detail the grounds for the objection, in any of the following cases:
1. it considers that the conduct of the study promotes the use of a medicinal product;
2. it considers that the design of the study does not fulfil the study objectives; or
c
a letter notifying the marketing authorisation holder that the study is a clinical trial falling under the scope of Directive 2001/20/EC.
3
The study may commence only when the written endorsement from the national competent authority or the Pharmacovigilance Risk Assessment Committee, as appropriate, has been issued.
Where a letter of endorsement as referred to in paragraph 2(a) has been issued, the marketing authorisation holder shall forward the protocol to the competent authorities of the Member States in which the study is to be conducted and may thereafter commence the study according to the endorsed protocol.
Article 107o
After a study has been commenced, any substantial amendments to the protocol shall be submitted, before their implementation, to the national competent authority or to the Pharmacovigilance Risk Assessment Committee, as appropriate. The national competent authority or the Pharmacovigilance Risk Assessment Committee, as appropriate, shall assess the amendments and inform the marketing authorisation holder of its endorsement or objection. Where applicable, the marketing authorisation holder shall inform Member States in which the study is conducted.
Article 107p
1
Upon completion of the study, a final study report shall be submitted to the national competent authority or the Pharmacovigilance Risk Assessment Committee within 12 months of the end of data collection unless a written waiver has been granted by the national competent authority or the Pharmacovigilance Risk Assessment Committee, as appropriate.
2
The marketing authorisation holder shall evaluate whether the results of the study have an impact on the marketing authorisation and shall, if necessary, submit to the national competent authorities an application to vary the marketing authorisation.
3
Together with the final study report, the marketing authorisation holder shall electronically submit an abstract of the study results to the national competent authority or the Pharmacovigilance Risk Assessment Committee.
Article 107q
1
Based on the results of the study and after consultation of the marketing authorisation holder, the Pharmacovigilance Risk Assessment Committee may make recommendations concerning the marketing authorisation, stating the reasons on which they are based. The recommendations shall mention the divergent positions and the grounds on which they are based.
2
When recommendations for the variation, suspension or revocation of the marketing authorisation are made for a medicinal product authorised by the Member States pursuant to this Directive, the Member States represented within the coordination group shall agree a position on the matter taking into account the recommendation referred to in paragraph 1 and including a timetable for the implementation of the agreed position.
If, within the coordination group, the Member States represented reach agreement on the action to be taken by consensus, the chairman shall record the agreement and send it to the marketing authorisation holder and the Member States. The Member States shall adopt necessary measures to vary, suspend or revoke the marketing authorisation concerned in accordance with the implementation timetable determined in the agreement.
In the event that a variation is agreed upon, the marketing authorisation holder shall submit to the national competent authorities an appropriate application for a variation, including an updated summary of product characteristics and package leaflet within the determined timetable for implementation.
The agreement shall be made public on the European medicines web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004.
If an agreement by consensus cannot be reached, the position of the majority of the Member States represented within the coordination group shall be forwarded to the Commission, which shall apply the procedure laid down in Articles 33 and 34.
Where the agreement reached by the Member States represented within the coordination group or the position of the majority of Member States differs from the recommendation of the Pharmacovigilance Risk Assessment Committee, the coordination group shall attach to the agreement or majority position a detailed explanation of the scientific grounds for the differences together with the recommendation.
Substituted by Directive 2010/84/EU of the European Parliament and of the Council of 15 December 2010 amending, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to medicinal products for human use (Text with EEA relevance).