VII.B.4. Reference information

Location:
VII.B.

Risk minimisation activities evaluated in the PSUR include updates to the product information.

The reference product information for the PSUR should include “core safety” and “authorised indications” components. In order to facilitate the assessment of benefit and risk-benefit balance by indication in the evaluation sections of the PSUR, the reference product information document should list all authorised indications in ICH countries4 or regions. When the PSUR is also submitted to other countries in which there are additional locally authorised indications, these indications may be either added to the reference product information or handled as a regional appendix as considered most appropriate by the marketing authorization holder. The basis for the benefit evaluation should be the baseline important efficacy and effectiveness information summarised in the PSUR section 17.1 (“Important baseline efficacy and effectiveness information”).

Information related to a specific indication, formulation or route of administration should be clearly identified in the reference product information.

The following possible options can be considered by the marketing authorisation holders when selecting the most appropriate reference product information for a PSUR:

  • Company core data sheet (CCDS)
    • It is common practice for marketing authorisation holders to prepare their own company core data sheet which covers data relating to safety, indications, dosing, pharmacology, and other information concerning the product. The core safety information contained within the CCDS is referred to as the company core safety information (CCSI). A practical option for the purpose of the PSUR is for each marketing authorisation holder to use the CCDS in effect at the end of the reporting interval, as reference product information for both the risk sections of the PSUR as well as the main authorised indications for which benefit is evaluated.
    • When the CCDS does not contain information on authorised indications, the marketing authorisation holder should clearly specify which document is used as reference information for the authorised indications in the PSUR.
  • Other options for the reference product information
    • When no CCDS or CCSI exist for a product (e.g. where the product is authorised in only one country or region, or for established/generics products on the market for many years), the marketing authorisation holder should clearly specify the reference information being used. This may comprise national or regional product information such as the EU summary of product characteristics (SmPC).
    • Where the reference information for the authorised indications is a separate document to the reference safety information (the core safety information contained within the reference product information), the version in effect at the end of the reporting interval should be included as an appendix to the PSUR (see VII.B.5.20.).

The marketing authorisation holder should continuously evaluate whether any revision of the reference product information/reference safety information is needed whenever new safety information is obtained during the reporting interval and ensure that significant changes made over the interval are described in PSUR section 4 (“Changes to the reference safety information”) and where relevant, discussed in PSUR section 16 (“Signal and risk evaluation”). These changes may include:

  • changes to contraindications, warnings/precautions sections;
  • addition to adverse reactions and interactions;
  • addition of important new information on use in overdose; and
  • removal of an indication or other restrictions for safety or lack of efficacy reasons.

The marketing authorisation holder should provide a clean copy of all versions of the reference product information in effect at the end of the reporting interval (e.g. different formulations included in the same PSUR) as an appendix to the PSUR (see VII.B.5.20.). The reference product information should be dated and version controlled.

Where new information on safety that could warrant changes to the authorised product information (e.g. new adverse drug reaction, warning or contraindication) has been added to the reference safety information during the period from the data lock point to the submission of the PSUR, this information should be included in the PSUR section 14 (“Late-breaking information”), if feasible.

If stipulated by applicable regional requirements, the marketing authorisation holder should provide, in the regional appendix, information on any final, ongoing and proposed changes to the national or local authorised product information (see VII.C.5.).