Regulatory Focus™ > News Articles > ICH Releases Final Safety Reporting Guidelines for International Adoption

ICH Releases Final Safety Reporting Guidelines for International Adoption

Posted 26 November 2012 | By Alexander Gaffney, RAC

The International Conference on Harmonisation (ICH), a pharmaceutical standards harmonization body consisting of the US, EU and Japan, has adopted two changes to its safety reporting guidelines, which now await adoption by regulators.

The two guidelines, E2B(R3) Clinical Safety Data Management: Data Elements for Transmission of Individual Case Safety Reports (ICSRs) and E2C(R2) Periodic Benefit-Risk Evaluation Report (PBRER), were finalized during the 10-15 November 2012 meeting on the ICH in San Diego, CA.

All three regulators-the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and Japan's Ministry of Health, Labour and Welfare-had released draft versions of the guidelines for comment in 2011 and 2012, respectively.

The E2B guideline was the first to undergo changes using a pilot process involving parallel review by multiple standards development organizations, ICH noted, most notably the Health Level 7 (HL7) standard on which the electronic transmission of ICSRs is based.

"Conceptually, an ICSR is a report of information describing adverse event(s) / reaction(s) experienced by an individual patient; the event(s)/reaction(s) can be related to the administration of one or more medicinal products at a particular point in time," the guideline explains. "The ICSR can also be used for exchange of other information, such as medication error(s) that do not involve adverse events(s)/reaction(s). The information for the report is provided by a primary source, although, depending on regional requirements, new information, or for practical or logistical issues, a given ICSR can be updated or retransmitted by either the initial sender or a 3rd party."

The implementation of the E2B guideline-now in Step 4 of the ICH process-will be overseen by Implementation Working Groups, ICH said.

The E2C guideline, meanwhile, was lauded by ICH officials for its unexpectedly rapid implementation. The entire revision process took less than two years-no small feat considering the complex problems addressed and the need to collect comments from three highly regulated regions.

The E2C guideline, "Defines the recommended content and format of a PBRER and provides an outline of points to be considered in its preparation and submission," the guideline explains.

PBRERs are necessary to bridge the knowledge gap between how a drug product performs in a trial and how it performs in real-world settings. Newer products, particularly those intended to treat large portions of the population, are generally approved based on trials involving ideal patients under ideal conditions. "Often, higher risk subgroups and patients with concomitant illnesses that require use of other drugs are excluded from clinical trials, and long-term treatment data are limited," ICH explained. It's therefore important for companies to keep regulators informed of how a product is actually performing in real world conditions, and if any safety or efficacy issues have come up unexpectedly.

Several other ICH guidelines also advanced to various stages of development. The organization's S10 Photosafety Evaluation of Pharmaceuticals guideline reached the Step 2 phase of development, and a draft guideline is expected to be released shortly. S1 Rodent Carcinogenicity Studies for Human Pharmaceuticals drafted a Regulatory Notice Document (RND), which, when published, will propose a change to ICH's carcinogenicity assessment approach and solicit public input. M7 Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk is reportedly just weeks away from reaching Step 2.

ICH's Q7 Good Manufacturing Practice (GMP) Guide for Active Pharmaceuticals is also in the early stages (Stage 1 or earlier) of revisions, as is the Q3D Metal Impurities document.

The next meeting of the ICH is scheduled for 1-6 June 2013 in Brussels, Belgium.

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