IDMP Wiki

ICSR in Pharmacovigilance

ICSR in Pharmacovigilance

Individual Case Study Report (ICSR) is an adverse event report for an individual patient and is source of data in pharmacovigilance.
The main focus of ICSRs are reports from healthcare providers and patients in member countries of the WHO Programme. A WHO global individual case safety report database (VigiBase) is maintained and developed on behalf of the WHO by the UMC.

VigiBase

VigiBase is the single largest drug safety data repository in the world. Since 1978, the Uppsala Monitoring Centre (UMC; established in Uppsala, Sweden) on behalf of WHO, have been maintaining VigiBase. Vigibase is used to obtain the information about a safety profile of a medicinal product. These data are used by pharmaceutical industries, academic institutions and regulatory authorities for statistical signal detection, updating periodic reports, ICSR comparisons with company databases and studying the reporting patterns. The data is collected from each of its 110 member states. About a hundred thousand ICSRs are added each year.

Adverse event reporting

One of the fundamental principles of adverse event reporting is the determination of what constitutes an Individual Case Safety Report (ICSR). During the triage phase of a potential adverse event report, it is important to determine if the “four elements” of a valid ICSR are present:

  1. an identifiable patient
  2. an identifiable reporter (called the “verbatim”)
  3. a suspect drug
  4. an adverse event

Seriousness determination

Although somewhat intuitive, there are a set of criteria within pharmacovigilance that are used to distinguish a serious adverse event from a non-serious one. An adverse event is considered serious if it meets one or more of the following criteria:

  • results in death, or is life-threatening
  • requires inpatient hospitalization or prolongation of existing hospitalization
  • results in persistent or significant disability or incapacity
  • results in a congenital anomaly (birth defect)
  • or is otherwise “medically significant” (i.e., that it does not meet preceding criteria, but is considered serious because treatment/intervention would be required to prevent one of the preceding criteria.)

ISO ICSR standard

Coding of adverse events

Adverse event coding is the process by which information from an adverse effect reporter, is coded using standardized terminology from a medical coding dictionary, such as MedDRA (the most commonly used medical coding dictionary). The purpose of medical coding is to convert adverse event information into terminology that can be readily identified and analyzed. For instance, Patient 1 may report that they had experienced “a very bad headache that felt like their head was being hit by a hammer” [Verbatim 1] when taking Drug X. Or, Patient 2 may report that they had experienced a “slight, throbbing headache that occurred daily at about two in the afternoon” [Verbatim 2] while taking Drug Y. Neither Verbatim 1 nor Verbatim 2 will exactly match a code in the MedDRA coding dictionary. However, both quotes describe different manifestations of a headache. As a result, in this example both quotes would be coded as PT Headache (PT = Preferred Term in MedDRA).

Please refer to dedicated webpage “Implementation of the ISO IDMP standards” on the EMA website for ongoing activities and next steps

Implementation of the ISO IDMP standards into ICSR

Safety monitoring of medicines in the European Union (EU)

The European Medicines Agency (EMA) has published a guide to support the implementation of a new international standard for the safety monitoring of medicines in the European Union (EU). The so-called ISO ICSR standard improves the reporting of suspected side effects of medicines in Individual Case Safety Reports (ICSRs). The use of the new international standard has taken effect on 1 July 2016. EMA is herewith closing the circle between ICSR and XEVMPD by using the ISO IDMP´s controlled vocabularies. It requires the use of the new ISO IDMP standards when they become available for use in the EU.

MPID – Medicinal Product Identifier

The interesting part for closing the circle between XEVMPD and ISCR is the so called MPID – Medicinal Product Identifier – also part of IDMP standard ISO 11615 identifying the product with ist entire liefe cycle (development, authorisation, post-Marketing and renewal or withdrawal from the market. Further it is stated that ‘until such a time as the ISO IDMP standards are implemented worldwide the support for free text will be required.
However, when the circle will be closed, then the aim of IDMP to increase the patients´safety will be reached.

ICSR Format

ISO ICSR aims at establishing the same format for the reports on individual cases of suspected side effects in patients due to a medicine across the world. It also is expected to include better information on medicines that might be associated with an adverse drug reaction and on the therapeutic uses of those medicines. In addition, the standard also strengthens personal data protection in the records of ICSRs collected by pharmaceutical companies and regulatory authorities.

This will improve the quality of data collected, and increase the ability to search and analyse them. Regulatory authorities will be able to detect and address safety issues with medicines more quickly, and therefore better protect patients.

EMA´s ICSR Implementation Guide

The new guide developed jointly by EMA and the Heads of Medicines Agencies (HMA) will be of interest to pharmaceutical companies and medicines regulatory authorities in EU Member States and will support them to prepare for the use of the standard. The guide specifically defines the electronic transmission process of ICSRs, the format and content of the ICSR, the business rules for report validation as well as classification and data quality principles. It will also assist software providers and IT developers as pharmacovigilance databases are being developed.

URL to the EU ICSR Implementation Guide

IDMP Wiki

Periodic Adverse Drug Experience Report PADER

Periodic Adverse Drug Experience Report PADER

Post-approval cumulative reports of safety include Periodic Adverse Drug Experience Reports (PADERs) in the U.S. and Periodic Safety Update
Reports (PSUR) in many other regions, including in Europe. Their purpose is to update and evaluate the worldwide safety experience with a medicine
at defined time points after approval. Generally speaking, the Periodic Adverse Drug Experience Report PADER provide succinct summary information together with an evaluation of the benefit-risk profile of approved medicines in the light of new or changing post-approval information. This evaluation is designed to help ascertain whether further investigations are necessary and whether changes should be made to the approval or to the medicine’s labeling. In summary, the aim of cumulative reports of safety is to:

  • Report all the relevant new information from appropriate sources
  • Relate these data to patient exposure to the medicine
  • Summarize the medicine’s approval status in different countries and any significant variations related to safety
  • Create periodically the opportunity for an overall reevaluation of safety
  • Indicate whether changes should be made to an approved medicine’s label in order to optimize the use of the product

FDA has started accepting PADER/PAER Submission in eCTD Format from June 10, 2015.

Electronic Format of the Periodic Adverse Drug Experience Report PADER

FDA requires Industries to submit Periodic Adverse Drug Experience Report PADER in electronic format
The descriptive information portion of the PADER should be submitted as a PDF file to section 5.3.6 of the Electronic Common Technical Document (eCTD)
PADER is a single pdf file with proper bookmarks, Table of Contents and hyperlinking Submission in Electronic Format for Post Marketing Safety Reports, applies to all post marketing safety report for human drug and biologic products, includes individual case safety reports(ICSRs) and periodic safety reports.

PSUR Repository

Planning and preparation of the PSUR

The use of the PSUR Repository has become mandatory in the European Union on 13 June 2016. The PSUR repository is a single, central platform for PSURs and related documents to be used by all regulatory authorities and pharmaceutical companies in the EU.

EMA´s  Introductory cover note to the PSUR submission defines the procedure and how PSURs should be prepared and submitted for medicinal products in Europe.

Information important for the submission of the PSUR

For more details on the submission process please refer to the page Periodic safety update reports: questions and answers in the EMA Website.

List of Union reference dates and frequency of submission of periodic safety update reports (PSURs)

The PSUR list is updated on a monthly basis and any changes in the EURD list, such as the PSUR submission frequencies, the dates of submission and the PSUR submission requirement for medicinal products referred to in Articles 10(1), 10a, 14 or 16a of Directive 2001/83/EC come into force 6 months after its publication.

Procedural Timetables of PSUR

This EMA page procedural timetables lists the timetables for the submission, start and finish dates of procedures, as well as other interim dates and milestones that occur during the various procedures.

Timetables are categorised according to the type of procedure (e.g. full applications, extensions and variations, as well as response timetables).

The dates for submission, start of the procedure and plenary meetings of the Committee for Medicinal Products for Human Use (CHMP), the Pharmacovigilance Risk Assessment Committee (PRAC) and the Committee for Advanced Therapies (CAT) are generally fixed, but the other dates may be subject to adjustment until the CHMP reaches the adoption of the final opinion for the individual application.

At the start of the procedure, the Agency will notify the applicant of the adopted final timetable in writing.

What will you find in this page?

  • Initial marketing authorisation and extension applications
  • Variations
  • Renewals and annual reassessments
  • Pharmacovigilance procedures
  • Referrals
  • Post-authorisation measures
  • Advanced therapy medicinal products (ATMPs) procedural timetables

PSUR Substances in the “Active Pharmaceutical Ingredients Dictionary”