Thiomersal (also known as thimerosal, merthiolate) is an organomercurial derivative of ethylmercury that has been used extensively over many years as a preservative in vaccines. Its primary purpose has been to prevent microbial growth in the product during storage and use, as well as to inactivate certain organisms and toxins during production.
In 1999, concerns were raised about exposure to mercury in vaccines, especially those given to infants. These concerns were based primarily on data regarding the toxicity of a related substance, methylmercury, and from data on chronic exposure to mercury from the food chain. Nevertheless, such safety concerns have led to initiatives in some countries to eliminate, reduce or replace thiomersal in both in single dose and multi-dose presentations. Although immune-mediated reactions to products containing mercury (mainly contact allergy as a manifestation of delayed-type hypersensitivity) can occur in some humans, this was not a major force leading to the recommendation by the authorities in some countries for the elimination of thiomersal from vaccines. It is important to note that concerns about the toxicity of thiomersal are theoretical and that there is no compelling scientific evidence of a safety problem related to its use in vaccines, although public perception of risk has been reported in some countries.
The decision to reduce or replace thiomersal has engendered considerable controversy. Thiomersal usage during production and as a preservative throughout the shelf life of the vaccines, may have hitherto unrecognized effects on active ingredients of the vaccine substance. The benefit of its removal must be carefully weighed against discarding the existing formulation with its proven safety and efficacy. The substitution of thiomersal with another preservative may, similarly, produce alternations in vaccine function or quality not predicted by its antimicrobial properties.
The Global Advisory Committee on Vaccine Safety (GACVS) first assessed this issue in a special meeting in August 2000 and continues to review the safety aspect of thiomersal-containing vaccines as new evidence emerges. In the latest review by the committee (at its meeting of 6-7 June 2006) the conclusion, which previously reached, was reaffirmed that there is no evidence of toxicity in infants, children or adults exposed to thiomersal in vaccines.
Regulatory expectations for thiomersal-containing vaccines
WHO developed a guidance document for thiomersal containing vaccines in 2003. This document describes the general principles of evaluating a vaccine following the elimination, reduction, removal or replacement of thiomersal from an already licensed vaccine with particular attention being paid to the regulatory expectations for each of the above possibilities.
Guidelines on regulatory expectations related to the elimination, reduction or replace of thiomersal in vaccines, TRS 926, Annex 4
Meeting Report: WHO Informal Consultation (3-4 April 2012) to develop further guidance on vaccines for UNEP-convened Intergovernmental Negotiating Committee Meeting 4 (INC 4)
Thiomersal WHO Consultation on the impact of thiomersal on quality, safety & efficacy of vaccines: regulatory perspectives, Geneva, 15-16 April 2002