Only valid ICSRs qualify for submission. In accordance with ICH-E2D (see GVP Annex IV), all reports of suspected adverse reactions should be validated before submitting them to the competent authorities to make sure that the minimum criteria are included in the reports.

Four minimum criteria are required for ICSRs validation:

a. one or more identifiable reporter (see VI.A.1.4. for primary source definition), characterised by parameters such as qualification (e.g. physician, pharmacist, other healthcare professional, lawyer, consumer or other non-healthcare professional), name, initials, or address (e.g. reporter’s organisation, department, street, city, state or province, postcode, country, email, phone number). Local data protection laws might apply.

In line with ICH-E2D, the term ‘identifiable’ indicates that the organisation notified about the case has sufficient evidence of the existence of the person who reports the facts based on the available information. In addition, in accordance with ICH E2B, an ICSR is not valid for submission unless information concerning the qualification and the country is available for at least one reporter. Thus, an ICSR is valid if the rules from ICH-E2D regarding the reporter’s identifiability and from ICH-E2B regarding the reporter’s qualification and country are fulfilled for at least one reporter. If information on the reporter’s qualification is missing, the notification should be considered by default as a consumer report. If information on the reporter’s country is not available, the country where the notification was received or where the review took place should be used in the ICSR. Whenever possible, contact details for the reporter should be recorded to facilitate follow-up activities. However, if the reporter does not wish to provide contact information, the ICSR should still be considered valid as long as the notified organisation is able to confirm the case directly with the reporter.

To enable duplicate detection activities, all parties providing case information or approached for case information should be recorded in the ICSR (not only the initial reporter).

When the information is based on second-hand or hearsay, the report should be considered nonvalid until it can be verified directly with the patient, the patient’s healthcare professional or a reporter who had direct contact with the patient.

b. one single identifiable patient, characterised by at least one of the following qualifying descriptors: initials, medical record number (from general practitioner, specialist, hospital, or investigation), date of birth, age, age group, gestation period, or gender. In line with ICH-E2D, the term ‘identifiable’ refers to the possibility of verification of the existence of a patient based on the available information.

The information should be as complete as possible in accordance with local data protection laws.

An ICSR should not be considered valid for submission unless information is available for at least one of the patient qualifying descriptors. Furthermore, as specified in ICH-E2D, in the absence of a qualifying descriptor, a notification referring to a definite number of patients should not be regarded valid until an individual patient can be characterised by one of the aforementioned qualifying descriptors for creating a valid ICSR.

c. one or more suspected substance/medicinal product (see VI.A.1.3. for definition). Interacting substances or medicinal products should also be considered suspected.

d. one or more suspected adverse reaction (see VI.A.1.1. for definition). If the primary source has made an explicit statement that a causal relationship between the medicinal product and the reported adverse event has been excluded and the notified competent authority or marketing authorisation holder agrees with this assessment, the report does not qualify as a valid ICSR since the minimum information for validation is incomplete (there is no suspected adverse reaction).

The report also does not qualify as a valid ICSR if it is reported that the patient experienced an unspecified adverse reaction and there is no information on the type of adverse reaction.

Similarly, the report is not valid if only an outcome (or consequence) is notified and (i) no further information about the clinical circumstances is provided to consider it as a suspected adverse reaction, or (ii) the primary source has not indicated a possible causal relationship with the suspected medicinal product. For instance a marketing authorisation holder is made aware that a patient was hospitalised or died, without any further information. In this particular situation, medical judgement should always be applied in deciding whether the notified information is an adverse reaction or an event. For example, a report of sudden death would usually need to be considered as a case of suspected adverse reaction and the valid ICSR should be submitted.

The lack of any of the four elements means that the case is considered incomplete and does not qualify for submission as ICSR. Competent authorities and marketing authorisation holders are expected to exercise due diligence in following-up the case to collect the missing data elements and follow-up activities should be documented. Reports, for which the minimum information is incomplete, should be recorded within the pharmacovigilance system for use in on-going safety evaluation activities.

When the missing information has been obtained (including for example when the medicinal product causal relationship with the reported adverse event is no longer excluded), the ICSR becomes valid for submission and the EU guidance provided in VI.C.6.2.3.8. should be followed.

Further guidance is available in VI.C.6.2.2.10. for the electronic submission in the EU of ICSRs where primary source information cannot be transmitted for data protection considerations.

When one party (competent authority or a marketing authorisation holder) is made aware that the primary source may also have reported the suspected adverse reaction to another concerned party, the valid report should still be submitted as ICSR. All the relevant information necessary for the detection of the duplicate case should be included in the ICSR. EU guidance on the electronic submission of information allowing the detection of duplicate ICSRs in line with ICH-E2B is provided in VI.C.6.2.2.6.

A valid case of suspected adverse reaction initially notified by a consumer cannot be downgraded to a report of non-related adverse event if a contacted healthcare professional (nominated by the consumer for follow-up information) subsequently disagrees with the consumer’s suspicion (see VI.A.1.1. for causality definition). In this situation, the opinions of both the consumer and the healthcare professional should be detailed in the narrative section of the ICSR. This information can also be submitted in a structured manner in ICH-E2B format, which provides the means to transmit the degree of suspected relatedness expressed by several primary sources for each reported drug event combination.

Similarly, a solicited report of suspected adverse reaction should not be downgraded to a report of non-related adverse event, when the notified recipient (competent authority or marketing authorisation holder) disagrees with the reasonable possibility of causal relationship expressed by the primary source on the supplied medicinal product. The opinions of both, the primary source and the recipient, should be recorded in the narrative section of the ICSR or in structured manner in line with ICH-E2B.

The same principle applies to the ICSR seriousness criterion, which should not be downgraded from serious to non-serious if the notified recipient disagrees with the seriousness reported by the primary source.