1. The marketing authorization holder shall be required to maintain detailed records of all suspected adverse reactions occurring either in the Community or in a third country.
2. The marketing authorization holder shall be required to record and to report all suspected serious adverse reactions which are brought to his attention by a health care professional immediately to the competent authority of the Member State in whose territory the incident occurred, and in no case later than 15 calendar days following the receipt of the information.
3. The marketing authorization holder shall be required to record and report all other suspected serious adverse reactions which meet the reporting criteria in accordance with the guidance referred to in Article 106(1) of which he can reasonably be expected to have knowledge immediately to the competent authority of the Member State in whose territory the incident occurred, and in no case later than 15 calendar days following the receipt of the information.
4. The marketing authorization holder shall ensure that all suspected serious and unexpected adverse reactions occurring in the territory of a third country and brought to his attention by a health care professional are reported immediately in accordance with the guidance referred to in Article 106(1), so that they are available to the Agency and to the competent authorities of the Member States where the medicinal product is authorised, and in no case later than 15 calendar days following the receipt of the information.
5. In the case of medicinal products which have been considered within the scope of Directive 87/22/EEC, or which have benefited from the procedures of mutual recognition foreseen in Articles 17 and 18 of this Directive, Article 28(4) of this Directive, and medicinal products for which there has been a referral to the procedures foreseen by Articles 32, 33 and 34 of this Directive, the marketing authorisation holder shall additionally ensure that all suspected serious adverse reactions occurring in the Community are reported in the format and at intervals to be agreed with the reference Member State, or a competent authority acting as the reference Member State, in such a way so as to be accessible to the reference Member State.
6. Unless other requirements have been laid down as a condition of the granting of authorisation, or subsequently as indicated in the guidance referred to in Article 106(1), records of all adverse reactions shall be submitted to the competent authorities in the form of a periodic safety update report, either immediately upon request or periodically as follows: six monthly for the first two years after authorisation, annually for the subsequent two years, and at the time of the first renewal. Thereafter the periodic safety update reports shall be submitted at five-yearly intervals together with the application for renewal of the authorisation. The periodic safety update reports shall include a scientific evaluation of the benefit and risks afforded by the medicinal products.
7. Following the granting of a marketing authorisation, the marketing authorisation holder may request the amendment of the periods referred to in this article according to the procedure laid down by Commission Regulation (EC) No 541/95(23).