Periodic safety update reports

E2C(R1) Clinical Safety Data Management Periodic Safety Update Reports for Marketed Drugs... 

Marketing authorisation holders are obliged to submit Periodic Safety Update Reports (PSURs) according to the frequencies outlined as follows ... 

Palazzini E Periodic Safety Update Report for Rixamin (January 1987-December 2003). Bologna, Alfa Wassermann, 2004. 

Clearly, therefore, those involved in drug safety monitoring need to liase closely with both clinical research and medical information scientists. In addition, those responsible for clinical drug safety must undertake periodic safety update reports (PSURs) at predetermined intervals, in accordance with current International Conference on Harmonisation (ICH) guidelines. Such routine analyses can identify new safety signals as soon as they become detectable. 

ICH Topic E2C Clinical Safety Data Management periodic safety update reports for marketed drugs. 

Specification (M2)], ICH/287/95 [Guidance on Clinical Safety Data Management Data Elements for Transmission of Individual Case Safety Reports (E2B)], ICH/288/95 [Guidance on Clinical Safety Data Management Periodic Safety Update Reports for Marketed Drugs (E2C)], and ICH/377/95 [Clinical Safety Data Management Definitions and Standards for Expedited Reporting (E2A)]. 

In the past decade, there has been increased emphasis on drug safety, and more public visibility of safety problems. The volume of reports now exceeds 250000 spontaneous reports per year, and adverse events are highlighted in the medical press and also in the general media. The FDA has released extensive proposed new regulations for post-approval reporting that in part move to harmonise requirements with ICH recommendations for periodic safety update reports (PSURs)... 

Eor spontaneous reports of reactions occurring in Australia, serious reactions (whether expected or unexpected) should be reported immediately and in no case later than 15 calendar days of receipt of the report. Other reactions occurring in Australia should be reported on request or as line listings in a Periodic Safety Update Report (PSUR). 

Guidelines on periodical safety update report (PSUR) introduced. Guidelines on stability for new formulations implemented. 

MAs are granted for five years in the first instance, after which a renewal is necessary. This requires submission of a review of all the product experience since the drug was first marketed. Essential parts of this review are the periodic safety update reports (PSURs), required every six months during the first two years of marketing, and annually thereafter. Normally, after the five-year renewal, further PSURs are required every five years. Under special circumstances more frequent PSURs may be required for products, which the authorities wish to keep under closer review. There is never any relaxation of the requirement for expedited reporting of serious, unexpected AEs. 

The data sheet is called the package insert in Japan, as it can be found in the drug packaging. The data sheet is drafted by the company and checked and completed by the authorities after the NDA review and the recommendation for approval. The content has been defined by the MHLW notification, and was revised in May 1997. Besides general information on the product, the most important entries are warnings, precautions and contraindications, and a list of adverse events quantitatively reported. These entries will be revised if necessary, with the safety data regularly analyzed for the periodic safety update report however, an ad hoc revision is made at any time in case of serious events. 

The type of ADR to report and the time limits are defined by the international guidelines on Safety Data Management. In addition, periodic safety update reports are sent to the MHLW with respect to these international standards. Traditionally, in Japan, ADRs are classified into three grades (mild, moderate, severe), according to severity criteria, and into function of the body apparatus. 

The dossier contains data from case report forms collected from hospitals. The number of cases is around 3000-4000 observations, reporting prescriptions on a routine basis (survey of use). Safety information comes from this particular survey and from spontaneous ADR reporting (serious events reports and the synthesis of the periodic safety update reports). Of course, information on measures taken during the period should be added (modification of the data sheet, etc.), as well as updated information regarding approval of the drug in foreign countries. 

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