ANNEX IIIU.K.SAFETY REPORTING
1.REPORTING OF SERIOUS ADVERSE EVENTS BY THE INVESTIGATOR TO THE SPONSORU.K.
1.The investigator does not need to actively monitor subjects for adverse events once the clinical trial has ended with regard to the subjects treated by him, unless otherwise provided for in the protocol.U.K.
2.REPORTING OF SUSPECTED UNEXPECTED SERIOUS ADVERSE REACTIONS (SUSARS) BY THE SPONSOR TO THE AGENCY IN ACCORDANCE WITH ARTICLE 42U.K.
2.1. Adverse Events and Causality U.K.
2.Medication errors, pregnancies and uses outside what is foreseen in the protocol, including misuse and abuse of the product, shall be subject to the same obligation to report as adverse reactions.U.K.
3.In determining whether an adverse event is an adverse reaction, consideration shall be given to whether there is a reasonable possibility of establishing a causal relationship between the event and the investigational medicinal product based on an analysis of available evidence.U.K.
4.In the absence of information on causality provided by the reporting investigator, the sponsor shall consult the reporting investigator and encourage him to express an opinion on this issue. The causality assessment given by the investigator shall not be downgraded by the sponsor. If the sponsor disagrees with the investigator's causality assessment, the opinion of both the investigator and the sponsor shall be provided with the report.U.K.
2.2. Expectedness, unexpectedness and the RSI U.K.
5.In determining whether an adverse event is unexpected, consideration shall be given to whether the event adds significant information on the specificity, increase of occurrence, or severity of a known, already documented serious adverse reaction.U.K.
6.The expectedness of an adverse reaction shall be set out by the sponsor in the RSI. Expectedness shall be determined on the basis of events previously observed with the active substance and not on the basis of the anticipated pharmacological properties of a medicinal product or events related to the subject's disease.U.K.
7.The RSI shall be contained in the SmPC or the IB. The covering letter shall refer to the location of the RSI in the application dossier. If the investigational medicinal product is authorised in several Member States concerned with different SmPCs, the sponsor shall select the most appropriate SmPC, with reference to subject safety, as the RSI.U.K.
8.The RSI may change during the conduct of a clinical trial. For the purpose of reporting SUSARs the version of the RSI at the moment of occurrence of the SUSAR shall apply. Thus, a change of the RSI impacts on the number of adverse reactions to be reported as SUSARs. Regarding the applicable RSI for the purpose of the annual safety report, see section 3 of this Annex.U.K.
9.If information on expectedness has been provided by the reporting investigator, this shall be taken into consideration by the sponsor.U.K.
2.3. Information for the reporting of SUSARs U.K.
10.The information shall at least include:U.K.
(a)
a valid EU trial number;
(b)
a sponsor study number;
(c)
an identifiable coded subject;
(d)
an identifiable reporter;
(e)
a SUSAR;
(f)
a suspect investigational medicinal product (including active substance name-code);
(g)
a causality assessment.
11.In addition, in order to properly process the report electronically, the following administrative information shall be provided:U.K.
(a)
the sender's (case) safety report unique identifier;
(b)
the receive date of the initial information from the primary source;
(c)
the receipt date of the most recent information;
(d)
the worldwide unique case identification number;
(e)
the sender identifier.