• Shirley-Ann Van Der Spuy, Qualified Person for Pharmacovigilance (QPPV) at Red Line Pharmacovigilance Ltd.
  • Esther Straghan, Associate Safety Risk Lead, Pfizer Ltd.
  • Manju Bhandari, Medical Information, Astellas Pharma Ltd.
  • Sarah Hall, Mipsol Ltd.
  • Cecilia Adetola, Medical Signatory Pharmacist, CK Management Ltd.
  • Sian Casey, a.i. Patient Safety Manager, Roche Products Ltd.
  • Sharon Braithwaite, PIPA Membership & Events Coordinator
  • Anne Turnbull, PIPA Operations Manager

Other types of report

Reports of overdose, abuse, off-label use, misuse, medication error and occupational exposure should be captured whether or not any suspected adverse reactions are reported at the same time.

  • If no associated adverse reaction is mentioned, these reports do not need to be submitted as ICSRs, but need to be discussed in PSURs as applicable.
  • Follow up incomplete reports for symptoms, treatments, outcomes, context of occurrence e.g. error in prescription, administration, dispensing, dosage, authorised indication or population.


Lack of Efficacy (or Lack of Effect)

Cases that do not result in adverse events should NOT be reported as ICSRs, however they should be captured in the PV system for further discussion in PSURs.

Follow up investigation may be required if reports are incomplete.

In some circumstances, lack of efficacy reports may need reporting within 15 day timeframe:

  • Medicinal products used in critical conditions/treatment of life threatening diseases
  • Vaccines
  • Contraceptives

Reporting is not required if the reporter has specifically stated that the outcome was due to disease progression and not related to the medicinal product, and the MAH agrees with the reporter’s assessment.

Clinical judgement to be used if other cases of lack of therapeutic effect qualify for reporting e.g. antibiotic used in a life-threatening situation where the medicinal product was not appropriate for the infective agent should not be reported.

However, a life-threatening infection, where the lack of therapeutic effect appears to be due to the development of a newly resistant strain of a bacterium previously regarded as susceptible, should be reported within 15 days.


Paediatric or Elderly

It is important to capture safety information on the use of medicinal products in vulnerable populations, such as the paediatric and elderly population groups.

Clinical trials are not usually conducted in children and the elderly. Thus data on the use of medication for these age groups is limited.

It is therefore important to obtain and submit age or age group of each patient, where possible, to help identify potential safety signals specific to a particular population or subset within a population

Paediatric age ranges are defined in the ICH E11 (‘Clinical Investigation for Medicinal Products in the Paediatric Population’) as follows:

  • Pre-term newborn infants
  • Newborn or neonate infants (0 to 27 days)
  • Infants and Toddlers (28 days to 23 months)
  • Children (2 to 11 years)
  • Adolescents (12 to 16 or 18 years – dependant on region)

The elderly (or geriatric) population comprises adults aged 65 years and older.

Thus, adults fall in the 18 – 65 year age category.

Additional guidance on Paediatric population considerations:

The EMA are currently creating additional guidance documentation relating to elderly populations.

Pregnancy and Breastfeeding

Clinical trials are unethical in pregnant patients and limited information is available on exposure via breastmilk. Thus any information on all pregnancy and breastfeeding cases should be collected and documented.

These cases include embryo or foetus exposure to medicinal products either through maternal exposure or via semen following paternal exposure and exposure via breastfeeding.

Follow up investigation is required on or around the expected delivery date to determine the outcome of the pregnancy and subsequent development of the exposed child after birth.

Detailed standard structured questionnaires specifically constructed for pregnancy cases are recommended.

Congenital abnormalities/developmental delay (foetus or child), foetal death and spontaneous abortion and suspected adverse reactions on neonate are all considered serious and should be reported

Reports of induced termination without congenital malformation, pregnancy exposure without abnormalities or those with normal foetal outcome should be collected and documented in PSURs. There is no requirement to submit these reports since there is no suspected ADR.

Certain circumstances, such as reports of pregnancy exposure with no suspected reactions may need reporting to competent authorities. Reporting of pregnancy exposure may be a condition of the MA or stipulated in the RMP such as where medicinal products need additional surveillance because of a high teratogenic potential (e.g. thalidomide, isotretinoin)

Signal of possible teratogenic effect e.g. through cluster of similar abnormal outcomes should be notified immediately to competent authorities with recommendations.

Key Elements for Data Quality

Good quality data means your company data is complete, consistent, accurate, time-stamped and follows industry standards.

  • Patient Confidentiality
  • Reporter identifiability (consider local data privacy laws)
  • Consider data security, strict access controls to documents and databases for authorised personnel
  • Consider PV data contract agreements (receipt confirmation and reconciliation)
  • Quality assurance of data entry and confirmation of proficiency
  • Audit trail of all data entered or modified (dates, sources, destinations)
  • Identification and management of duplicates
  • Quality Management system for data collection, transfer, management, coding, validation, evaluation, follow up, reporting and archiving
  • Source data needs to be easily accessible e.g. letters, emails, records of telephone calls, image and source data
  • Clear SOPs required for roles and responsibilities and kept up to date. Include 3rd parties (compliant with applicable requirements)
  • PV staff appropriately trained in relevant PV legislation and guidelines together with relevant report processing activities
  • Training of other personnel who may receive / process safety reports e.g. Clinical Development, Sales, Medical Information, Legal, Quality Control.

Organised Data Collection Systems

Solicited reports are obtained from any organised data collection system and reports of adverse reactions from these systems are not considered spontaneous.

The exceptions to this rule includes any adverse reaction reports from compassionate use or named patient use where the systemic adverse event reports in these programmes are not required and reported from non-interventional post-authorisation studies related to specified adverse events for which the protocol does not require their systematic colleaction.

Thus, sources of solicited reports include:

  • Clinical trials
  • Non-interventional Studies
  • Registries
  • Post-approval Named Patient Use Programmes
  • Other Patient Support and Disease Management Programmes
  • Surveys of Patients or Healthcare Providers / Market Research
  • Compassionate Use or Named Patient Use
  • Information Gathering on Efficacy or Patient Compliance

Solicited reports are classified as study reports and should therefore have an appropriate causality assessment.

Literature Case Reports

  • Every MAH is required to maintain an awareness of publications through reference databases e.g. Medline, Excerpta Medica or Embase – no less frequently than once a week.
  • Literature review should include databases that contain a large library of articles in relation to medicinal product properties.
  • Monitoring of scientific and medical publications in local journals in countries where medical products have a MA should take place. In order to do this, the MAH should establish the most relevant source of published literature for each product.
  • Screening should also include a review of published abstracts from meetings and draft manuscripts. Although it is not a requirement to attend such meetings, if company personnel are at a meeting or a company has sponsored a meeting, they would be expected to capture all adverse event data from the meeting relevent to the MAH’s products. Where a company sponsors a meeting it is expected that they will be able to review abstracts prior to the meeting.
  • If multiple medicinal products are listed within a publication, only the product(s) with a possible causal relationship with the suspected adverse reaction are required to be logged.
  • Where articles include many patients, one case for each identifiable patient should be entered and the publication author(s) should be considered as primary source(s).

ICSR Reporting throughout the Life-Cycle of the Product

Certain special situations may arise during the life-cycle of a medicinal product. Areas of responsibility for the MAH related to the collection of safety data begin on the submission of an application for product licence (i.e. prior to approval) and continue well beyond product withdrawal from the market

  • During the period between submission of MA application and granting of MAthe MAH is required to report any information (quality, non-clinical and clinical) that could impact on the risk-benefit of the product

In the situation where an MA application is under evaluation in the EU while it has already been authorised in a third country, valid ICSRs from outside the EU should be submitted to EudraVigilance

  • During the period after suspension, revocation or withdrawal of MAthe MAH must continue to collect any spontaneous reports (i.e. for possible adverse reactions with a delayed onset)
  • Any period during a public health emergency regular reporting requirements may be amended, the details of which are considered on a case-by-case basis and which will be notified on agency website
  • Class action lawsuits may stimulate spontaneous reporting and valid reports describing adverse reactions should still be reported in accordance with timeframes
  • Patient Support and Market Research Programmes are organised systems for collecting information about medicinal products, as such reports from these sources should be considered as solicited reports and valid cases with causal relationship should be reported.

Submitting ICSR Reports

Serious ICSRs

  • All serious reports occurring within or outside EU, including those received from competent authorities outside EU, should be reported directly to EudraVigilance database.
  • Competent authorities in Member States (MS) submit all serious reports to EudraVigilance that occur in their territory and that are directly reported to them.

Non-serious ICSRs

  • All non-serious reports occurring within EU should be reported to EudraVigilance database only
  • Competent authorities in MS submit all non-serious reports occurring in their territory and that are directly reported to them to Eudravigilance database

Reporting to Individual Member States

Unless there are justifiable grounds resulting from PV activities, individual member states shall not impose any additional obligations on MAHs for the reporting of suspected ADRs.