advanced search

<< Back To Home

THE SAFETY OF THIOMERSAL

Monday, 31st of October 2011

On behalf of the GAVI Civil Society Constituency, the GAVI Civil Society Steering Committee endorses the attached letter on thiomersal in vaccines and expresses concern regarding a provision in the draft text of the UNEP legally binding instrument on mercury that could significantly limit access to lifesaving vaccines in poor countries. 

The GAVI Civil Society Constituency includes over 200 organisations across the globe working to reach every child with immunisation.  The Constituency’s Steering Committee includes 20 national and international partners working to improve maternal and child health:

 

Aga Khan Health Services (Pakistan)

Alternative Santé (Cameroon)

Catholic Relief Services (USA)

Centre for Health Policy and Innovation (South Africa)

Communications for Development Centre (Nigeria)

Consortium of Christian Relief and Development Association (Ethiopia)

Future Generations International (Ghana)

Health N’ Rights Education Program (Malawi)

HealthNet TPO (Afghanistan)

Indian Academy of Paediatrics (India)

International Federation of Red Cross and Red Crescent Societies (Switzerland)

International Pediatric Association

Médecins sans Frontières

Oxfam Ghana (Ghana)

Réseau des Platformes Nationales d’ONG d’Afrique de l’Ouest et du Centre (REPAOC) (Senegal)

Save the Children UK (U.K.)

Task Force for Global Health (USA)

Uganda Pediatric Association (Uganda)

World Vision (Germany)

Thursday, October 06, 2011

Mr. Fernando Lugris

Chair, Intergovernmental Negotiating Committee

United Nations Environment Programme

Ministro Consejero

Embajada de Uruguay

Budapest Street No. 32

10787 Berlin

Germany

 

Dear Honorable Chair Lugris,

Recognizing the harms of some types of mercury, we commend the United Nations Environment

Programme for supporting the work to prepare a legally binding instrument on mercury.

However, as organizations committed to protecting the health of people worldwide, we have

grave concerns about language in the draft treaty that would limit the availability of vaccines

containing mercury-added products. As you are likely aware, vaccines are one of the most costeffective and important medical interventions to prevent infectious diseases worldwide.

 

As we

strive to expand access to safe and effective vaccines, it is critical that any policies that may limit access accurately reflect the relevant science.

We understand that this treaty could include a ban on thiomersal, a preservative included in

vaccines that protect more than 80 million infants from deadly diseases each year. Thiomersal is an ethylmercury-containing antimicrobial compound used to prevent bacterial and fungal growth in some vaccine vials. Some anti-thiomersal activists have confused ethylmercury with methylmercury. Methylmercury is a known neurotoxin that can cause serious health problems.

 

There is no evidence that suggests the amount of ethylmercury found in thiomersal-containing

vaccines is harmful to human health.

 

Over the past ten years, reputable scientific bodies have evaluated the safety of thiomersal. The World Health Organization’s (WHO’s) Global Advisory Committee on Vaccine Safety

concludes that existing thiomersal-containing vaccines are safe and that any risks are unproven.

 

Similar conclusions have been drawn by the US Institute of Medicine, the American Academy of Pediatrics, the UK Committee on Safety of Medicines, and the European Medicines Agency.

 

The implications of restricting the manufacture, distribution, or use of thiomersal could

significantly limit access to several lifesaving vaccines in poor countries. According to WHO,

making vaccines thiomersal free would require either using an alternative preservative (which

would require costly and time-consuming clinical studies, thereby driving up the cost of the

vaccines) or using preservative-free single-dose vaccines exclusively (which would considerably increase costs and require twice the storage and transport capacity, an impossibility for most countries). Neither of these scenarios is desirable, particularly given that there is no evidence to suggest that removing thiomersal from vaccines would result in a positive health impact.

We urge the Intergovernmental Negotiating Committee to consider the scientific evidence

provided by WHO as it negotiates the treaty on mercury.

 

We invite you to contact Erin Fry at efry@path.org with any questions.

 

Enclosure: United Nations Environment Programme. Intergovernmental negotiating committee to prepare a global legally binding instrument on mercury, third session. Annex 1: Mercury in human vaccine preservatives (submitted by WHO). Nairobi, Kenya; 2011.

 

Available at:

http://www.unep.org/hazardoussubstances/Portals/9/Mercury/Documents/INC3/3_6_health_advance.pdf.

 

Sincerely,

 

Global Implementing and Advocacy Organizations

PATH (Global)

Agence de Médecine Préventive (Global)

 

Professional Associations and Research Programs

American Academy of Pediatrics (US)

International Pediatric Association (Global)

Pediatric Infectious Diseases Society (US)

American Society of Tropical Medicine (US)

National Association of City and County Health

Officials (US)

Infectious Diseases Society of America (US)

Sabin Vaccine Institute (Global)

Aeras (Global)

International AIDS Vaccine Initiative (Global)

World Vision (Global) United Nations Foundation Shot@Life (Global)

American Red Cross (US)

ONE (Global)

International Vaccine Access Center (Global) John Snow, Inc. (Global)

Management Sciences for Health (Global) Global Alliance to Prevent Prematurity and Stillbirth

(Global)

Global Health Visions (Global) Results (US)

Results United Kingdom (UK) Results Canada (Canada)

 

Regional, Country and Local Organizations

ADVocacy for IMmunization (Western Africa)

Réseau International Epivac (Francophone Africa)

Health and Rights Education Program (Malawi)

Kenya AIDS NGOs Consortium (Kenya)

National Meningitis Association (US)

Centre for Health Policy and Innovation (South

Africa)

National Foundation for Infectious Diseases (US)

SMLS Trust of Amalapuram (India)

Parents of Kids with Infectious Diseases (US)

Every Child By Two (US)

The Immunization Partnership (US)

Tulsa Area Immunization Coalition (US)

Hawaii Immunization Coalition (US)

New Jersey Immunization Network (US)

Immunization Action Coalition (US)

California Immunization Coalition (US)

People Welfare Services (Cameroon)

P

UNEP(DTIE)/Hg/INC.3/6

Annex I

Mercury in human vaccine preservatives (submitted by WHO)

 

Background

1. Thiomersal (also known as thimerosal, mercurothiolate and sodium 2-ethylmercuriothiobenzoate)

is an ethyl mercury-containing antimicrobial compound used to prevent bacterial and fungal

growth in some vaccines during storage, and especially during use of opened multi-dose vials. It is

also used during vaccine production both to inactivate certain organisms and toxins and to maintain a

sterile production line. Thiomersal has been used since the 1930s in the manufacture of some vaccines

and other medicinal products.

 

Why do vaccines need preservatives?

2. In many countries, for multi-dose vaccines, other than live vaccines, the presence of a

preservative is a regulatory requirement. Preservatives inhibit growth of bacterial and fungal

contamination, which may be introduced during repeated puncture of a multi-dose vial septum. While

a preservative is needed only for multi-dose presentations, a manufacturer will usually make one bulk

formulation, so if the product has both multi-dose and single dose presentations, the single dose

presentation would also contain preservative.

3. Opened vials of vaccines without preservatives need to be discarded at six hours from opening

or at the end of the immunization session, whichever is earlier. The presence of a suitable preservative

means that opened multi-dose vials may be kept for use in subsequent immunization sessions (WHO

policy statement, 2000). This minimizes wastage and can have a significant impact on programme

costs. Based on known patterns of vaccine administration in different countries WHO estimates that at

least 30% of vaccine doses required can be saved through application of this policy to preserved

multi-dose vials.

 

Very small amounts of mercury are used for vaccine preservative

4. Vaccines that contain thiomersal include those against diphtheria, tetanus and pertussis (DTP),

hepatitis B, Haemophilus influenzae type b (Hib), rabies, influenza and meningococcal diseases.

Usually, these have thiomersal added in varying concentrations (8 to 50 μg per dose) as a preservative.

This list is not exhaustive, but highlights vaccines of major global public health importance. Also,

some vaccines may contain trace amounts of thiomersal (<0.5 μg per dose), if it has been used in the

production process as an inactivating agent, but has not been added to the final product as a

preservative.

5. Currently thiomersal-containing vaccines are supplied by the United Nations (UNICEF and

WHO Regional Office for the Americas in particular) with multi-dose presentations of thiomersal

containing vaccines. These vaccines form the basis of the prevention of at least four major killers of

infants and children (diphtheria, tetanus, pertussis, Haemophilus influenzae type b disease and

influenza) and one other important disease (hepatitis B). During 2010, UNICEF alone supplied over

300 million doses of vaccines against those diseases either for routine vaccination activities or for

response against outbreaks of infectious diseases such as influenza or epidemic meningitis.

6. Data from the European Union, where two large manufacturers of inactivated vaccines are

located, reveal that the total quantity of thiomersal utilized by members of European Vaccine

Manufacturers (EVM) is less than 0.25 ton per year corresponding to 0.125 ton of mercury. A

significant part of this is used for vaccines exported to developing countries. In summary, the

quantities of mercury involved with vaccine preservatives are fairly small.

 

Safety of thiomersal

7. Health risks related to the use of thiomersal in vaccines have been reviewed on numerous

occasions. In 1999, concerns were raised in the United States of America regarding exposure to

mercury following immunization with thiomersal-containing vaccines. This was based on the

calculation that the cumulative amount of mercury in infant immunization schedules potentially

exceeds the recommended threshold for methyl mercury set by a USA government agency. However,

thiomersal contains ethyl mercury, not methyl mercury. The pharmacokinetics of ethyl and methyl

mercury are quite different. In particular, the half-life of ethyl mercury is short (6 days; 95% CI: 3-10

days) compared with 40-50 days for methyl mercury. Ethyl mercury is actively excreted into the

intestinal tract and not accumulated in the body.

8. Since August 2000, the WHO Global Advisory Committee on Vaccine Safety (GACVS) has

periodically reviewed available information on thiomersal pharmacokinetic studies in humans

(including low birthweight infants) and in monkeys and has assessed the validity of animal models in

studying associations between thiomersal and neurobehavioural disorders in humans:

• • Expert consultation and data presented to the GACVS indicate that the

pharmacokinetic profile of ethyl mercury is substantially different from that of methyl

mercury. The half-life of ethyl mercury is shorter compared to methyl mercury (see

above) making exposure to ethyl mercury in blood comparatively brief and preventing

accumulation when vaccines are administered at least four weeks apart. Further, ethyl

mercury is actively excreted via the gut unlike methyl mercury that accumulates in the

body. This rapid elimination of ethyl mercury has been confirmed in all studies

reviewed, even those that looked at low birthweight infants.

• • Four independent epidemiological studies investigating associations and frequency of

neurobehavioural disorders in relation to vaccination with thiomersal-containing

vaccines from the United Kingdom and Denmark did not challenge the safety of

existing thiomersal-containing vaccines in infants. In particular analyses in the U.K. of

the General Practice Research Database (GPRD) and of the data set of the Avon

Longitudinal Study of Pregnancy and Childhood (ALSPAC) suggest that there is no

association between developmental delay, adverse neurological developmental

outcomes or behavioural problems, and thiomersal-containing diphtheria–pertussis–

tetanus vaccines.

• • GACVS also reviewed a series of studies by Geier and Geier alleging reduction of

neurodevelopmental disorders in the United States of America following

discontinuation of thiomersal-containing vaccines in the national immunization

programme. The Committee found a number of limitations, including: inaccessibility

to the reader of the data on which the analysis was made; lack of clear case definitions

for the conditions referred to in the paper; unclear or insufficient description of applied

statistical methods; assumption made by the authors that the toxicity of ethyl-mercury

is equivalent to that of methyl-mercury (an assumption that cannot necessarily be

made, and against which various authorities have warned); assumption in the paper

that the populations under study are similar (there is every possibility in the methods

used of selection bias); and a failure to account for changing reporting patterns for

diseases attributed to the vaccines over the years of the study. Published outcomes

regarding neurodevelopment and heart disease following administration of thiomersalcontaining

vaccines do not meet the scientific criteria required to suggest causal

relationship. The Committee therefore found the conclusions made by these authors

unconvincing.

 

9. On that basis the GACVS considers that pharmacokinetic and developmental studies do not

support concerns over the safety of thiomersal in vaccines. The Committee concludes, and advises

accordingly, that there is no reason on grounds of safety to change current immunization practices

with thiomersal-containing vaccines, as the risks are unproven.

 

10. Similar conclusions were reached by other respected advisory committees such as those from:

• U.S. Institute of Medicine (2001). "The hypothesis that thimerosal exposure through

the recommended childhood immunization schedule has caused neurodevelopmental

disorders is not supported by clinical or experimental evidence."

• American Academy of Pediatrics (2003). "No scientific data link thimerosal used as a

preservative in vaccines with any pediatric neurologic disorder, including autism."

• UK Committee on Safety of Medicine (2003). "There is no evidence of harm caused by

doses of thiomersal in vaccines, except for hypersensitivity reactions (such as allergic

skin reactions). There is no evidence of a link between hypersensitivity reactions and

the development of autism."

• European Agency for the Evaluation of Medicinal Products (2004). "Recent Evidence

Supports Safety of Thiomersal Containing Vaccines."

 

Public health implications of restricting manufacture, distribution or use of thiomersal-containing

vaccines

11. Thiomersal-containing vaccines are the most commonly used form of vaccine presentation to

protect more than 80 million infants from deadly diseases every year. Making vaccines thiomersal free

would require either using alternative preservatives (2-phenoxyethanol, phenol and benzethonium

chloride are preservatives used in a small number of other licensed vaccines) or using preservativefree

single dose vaccines exclusively.

 

12. However, either of the above changes to products currently formulated with thiomersal would

require regulatory approval (WHO - Guidelines on regulatory expectations related to the elimination,

reduction or replacement of thiomersal in vaccines, 2004). There is no guarantee of obtaining a

vaccine of equivalent quality, safety and efficacy following replacement of thiomersal as an

inactivating agent or replacement or removal of thiomersal as the preservative from an existing

licensed product. This could require a new licensing application, including conducting of new

manufacturing validation studies; pre-clinical and clinical studies. This is time consuming and costly,

could lead to an increase in vaccine cost and could interrupt global supply of the vaccines.

 

13. Vaccines could be supplied in preservative-free single-dose vials as is the case for the majority

of vaccines used in industrialized countries. This option, however, requires a significant increase in

manufacturers' filling capacity. This would be time consuming and expensive to implement and it may

not be possible to produce sufficient single dose product to ensure uninterrupted global supply.

Vaccines supplied in single dose vials are more expensive than a dose of vaccine from a multi-dose

vial. In addition, single-dose vials require significantly larger cold storage space as well as increased

transport capacity, which is currently not feasible for the majority of countries. Current WHO

estimates suggest that the vaccine storage requirements would at least double if single dose

presentations only were used (WHO vaccine volume calculator, March 2011). Upgrading the cold

chains of those countries is limited by local resources and the additional maintenance requirements

that would render many existing systems vulnerable.

 

WHO position on the use of thiomersal in vaccines

14. The assessment of thiomersal as a preservative for vaccines suggests that the amount of

mercury involved with thiomersal use in vaccines is small compared to other sources of mercury.

15. WHO has closely monitored scientific evidence related to the use of thiomersal as a

preservative for multi-dose inactivated vaccine presentations for over ten years, in particular through

its independent expert advisory group GACVS. Although many alleged risks have been studied in

detail in different groups of infants, there is no evidence that suggest a possible health hazard with the

amounts of thiomersal currently used, in particular no developmental nor neurological defects have

been related to the use of this compound.

16. WHO recommends multi-dose vaccine vials for the routine immunization programs in many

countries because they are safe and effective, they limit the required storage capacity and help reduce

vaccine costs. There is no likelihood of timely supply of sufficient alternative thiomersal-free

presentations of inactivated vaccines. Alternative presentations would incur significantly higher costs

in manufacturing procedures and regulatory approval, thereby limiting the ability to offer affordable

vaccines against major killer diseases where those products are the most needed.

UNEP DTIE Chemicals Branch and WHO Department of Food Safety, Zoonoses and Foodborne

Diseases 2008. Guidance for identifying populations at risk from mercury exposure.

http://www.who.int/entity/foodsafety/publications/chem/mercuryexposure.pdf

European Commission Directorate-General Environment 2008. Options for reducing mercury use in

products and applications, and the fate of mercury already circulating in society. Final report.

http://ec.europa.eu/environment/chemicals/mercury/pdf/study_report2008.pdf

WHO 2000. WHO Policy Statement - The use of opened multi-dose vials of vaccine in subsequent

immunization sessions.

http://www.who.int/vaccines-documents/DocsPDF99/www9924.pdf

WHO Global Advisory Committee on Vaccine Safety (2006). Statement on thiomersal

The Global Advisory Committee on Vaccine Safety concludes that there is no evidence of toxicity in

infants, children or adults exposed to thiomersal (containing ethyl mercury) in vaccines.

http://www.who.int/vaccine_safety/topics/thiomersal/statement_jul2006/en/index.html

WHO Global Advisory Committee on Vaccine Safety (2006). Thiomersal and vaccines: questions and

answers.

http://www.who.int/vaccine_safety/topics/thiomersal/questions/en/index.html

WHO Global Advisory Committee on Vaccine Safety. Meeting reports from December 2004, June

2005 and June 2008.

http://www.who.int/wer/2008/wer8332.pdf

http://www.who.int/wer/2005/wer8028.pdf

http://www.who.int/wer/2005/wer8001.pdf

WHO Expert Committee on Biological Standardization (2004). Fifty-third Report. Annex 4

Guidelines on regulatory expectations related to the elimination, reduction or replacement of

thiomersal in vaccines. PP 95-102.

http://whqlibdoc.who.int/trs/WHO_TRS_926.pdf

Knezevic I, Griffith E, Reigel F, Dobbelaer R (2003). Thiomersal in vaccines: a regulatory perspective

(meeting report).

http://www.who.int/biologicals/publications/meetings/areas/vaccines/thiomersal/Thiomersal_WHO_C

onsult%20April%2015_16_April2002.pdf

WHO. Vaccine volume calculator.

http://www.who.int/immunization_delivery/systems_policy/logistics/en/index4.html

WHO. Guidelines on regulatory expectations related to the elimination, reduction or replacement of

thiomersal in vaccines, 2004). WHO Technical Report Series, No. 926, 2004.

http://www.who.int/biologicals/publications/trs/areas/vaccines/thiomersal/Annex%204%20(95-

102)TRS926thiomersal.pdf