Guidance: Drug Safety

Recent US FDA guidance on safety testing of drug metabolites [5] highlights the importance of measuring major metabolites in human and toxicological species. This increased scrutiny on the role of metabolites in the evaluation of efficacy and safety will lead to increasing demand for metabolites as analytical standards. 

ICH E2C and FDA March 2001 draft guidance Postmarketing Safety Reporting for Human Drug and Biological Products Including Vaccines are available at www.fda.gov/cder/guidance/index.htm case requirements are accessible in 21 CFR 314.80. 

Cavero, I. and Crumb, W. (2005) The use of electrocardiograms in clinical trials a public discussion of the proposed ICH E14 regulatory guidance Expert Opinion on Drug Safety, 4, 795-799. 

To fulfill this commitment, FDA issued for comment a draft guidance titled FDA s Drug Watch for Emerging Drug Safety Information in May... 

FDA has carefully reviewed the comments it received on the draft guidance (30 comments were submitted to the public docket)6 and during the public hearing. This final version of the guidance reflects our consideration of these comments, as well as our experience with posting emerging drug safety information. 

FDA—Draft Guidance on Safety Testing on Drug Metabolites is Published... 

FDA—Guidance on Safety Testing on No major changes to recommendations Drug Metabolites is Published provided in the Draft Guidance. 

FDA s guidance on safety testing on drug metabolites (Food and Drug Administration, 2008), Metabolites that form chemically reactive intermediates can be difficult to detect and measure because of their short half-lives. However, they can form stable products (e.g., glutathione conjugates) that can be measured and, therefore, may eliminate the need for further evaluation. ... 

The pathway to assuring the safe and effective use of short-lived radiotracers is to place the responsibility for quality assurance in the hands of nuclear pharmacists who fill physician s prescriptions for radiotracers as they do for other drugs under state pharmacy laws. Radiochemists or others working in institutions with radiopharmacies must have the expertise for the preparation of the radiotracers as well as for quality control under good manufacturing practices. This hook provides guidance and safety standards applicable to Tc-99m pharmaceuticals. 

In the European Union (EU), the Committee on Proprietary Medicinal Products (CPMP) issued a draft Note for Guidance on Safety Pharmacology Studies in Medicinal Product Development in 1997 [3], but it was not finalized or put in force until the middle of 2001. The U.S. Food and Drug Administration (FDA) promulgated equivalent guidance at the same time, but the exact details of compliance and implementation, as will be seen in this volume, are still being worked out. 

CDER, Guidance for Safety Testing of Drug Metabolites, 2008. 

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