Tamiflu & the Environment: Implications of Use under Pandemic Conditions

Why the workshop?

Should an avian flu virus re-assort into a human flu virus, pandemic conditions could arise in thehuman population worldwide. Tamiflu™ and other antivirals have been developed to limit the spread of infection, decrease the incidence of flu-related complications, and ameliorate symptoms. These are being stockpiled around the world in readiness for use during a pandemic. Following administration, up to 80% of the Tamiflu™ dose received is expected to be excreted in the form of the metabolite and active antiviral, oseltamivir carboxylate (OC). A number of properties of Tamiflu™ (oseltamivir phosphate) and OC, including high solubility and low biodegradability mean that they are expected to pass through sewage treatment works and remain in this form in rivers.

Calculations of the concentrations of OC to be expected in rivers in the event of mass administration of Tamiflu™ have recently been published. The results provide a basis for concern about possible ecotoxicological effects and the potential development of viral resistance. The risks in a densely populated island such as mainland Britain are likely to be amongst the highest in the developed world. In order to better understand Tamiflu™ release into the environment and evaluate associated risks to human health and the ecosphere, a wide range of experts and organisations need to be actively involved. Early action and holistic thinking about the issues is likely to lead to a more effective
pandemic flu strategy and help to ensure that humans and the environment are protected to the greatest extent possible.

What is the workshop expected to achieve?

The workshop will assess the implications of Tamiflu™ release into the environment following mass administration under pandemic flu conditions. This will be done by addressing the following sequence of questions:
What are the implications for ecosystem and human health?
Are they significant enough to warrant further research?
If so, what research would be needed?
In the light of any implications, do pandemic influenza strategies need to be reviewed?
By bringing together a wide range of organizations and relevant areas of expertise, it is expected that the implications of Tamiflu™ release into the environment can be prioritized and further actions identified.

The programme for the workshop was as follows (full presentations can be found here):

An overview of the risks relating to Tamiflu release into the environment
Dr. Andrew SInger
Centre for Ecology & Hydrology

Antivirals and their use in pandemic influenza strategy: benefits and risks
Prof. John Oxford
Retroscreen Virology Ltd.

Assessing the environmental effects of human pharmaceuticals: current practice & opportunities for improved approaches
Prof. Tom Hutchinson
AstraZeneca

A preliminary environmental risk assessment for Tamiflu
Jurg Oliver Straub
F. Hofflmann La Roche Ltd.

An environmental regulator’s perspective on the risk of Tamiflu use under pandemic conditions
Dr. Tatiana Boucard
Environment Agency

Trying to identify high risk areas at the regional, catchment and river reach level
Dr. Andrew Johnson
Centre for Ecology & Hydrology

The workshop resulted in a publication in Environmental Health Perspectives:

Meeting Report: Risk Assessment of Tamiflu Use Under Pandemic Conditions

On 3 October 2007, 40 participants with diverse expertise attended the workshop Tamiflu and the Environment: Implications of Use under Pandemic Conditions to assess the potential human health impact and environmental hazards associated with use of Tamiflu during an influenza pandemic. Based on the identification and risk-ranking of knowledge gaps, the consensus was that oseltamivir ethylester-phosphate (OE-P) and oseltamivir carboxylate (OC) were unlikely to pose an ecotoxicologic hazard to freshwater organisms. OC in river water might hasten the generation of OC-resistance in wildfowl, but this possibility seems less likely than the potential disruption that could be posed by OC and other pharmaceuticals to the operation of sewage treatment plants. The work-group members agreed on the following research priorities: a) available data on the ecotoxicology of OE-P and OC should be published; b) risk should be assessed for OC-contaminated river water generating OC-resistant viruses in wildfowl; c) sewage treatment plant functioning due to microbial inhibition by neuraminidase inhibitors and other antimicrobials used during a pandemic should be investigated; and d) realistic worst-case exposure scenarios should be developed. Additional modeling would be useful to identify localized areas within river catchments that might be prone to high pharmaceutical concentrations in sewage treatment plant effluent. Ongoing seasonal use of Tamiflu in Japan offers opportunities for researchers to assess how much OC enters and persists in the aquatic environment.

Why the workshop?
Should an avian flu virus re-assort into a human flu virus, pandemic conditions could arise in the
human population worldwide. Tamiflu™ and other antivirals have been developed to limit the spread of
infection, decrease the incidence of flu-related complications, and ameliorate symptoms. These are
being stockpiled around the world in readiness for use during a pandemic.
Following administration, up to 80% of the Tamiflu™ dose received is expected to be excreted in the
form of the metabolite and active antiviral, oseltamivir carboxylate (OC). A number of properties of
Tamiflu™ (oseltamivir phosphate) and OC, including high solubility and low biodegradability mean that
they are expected to pass through sewage treatment works and remain in this form in rivers.
Calculations of the concentrations of OC to be expected in rivers in the event of mass administration of
Tamiflu™ have recently been published. The results provide a basis for concern about possible
ecotoxicological effects and the potential development of viral resistance. The risks in a densely
populated island such as mainland Britain are likely to be amongst the highest in the developed world.
In order to better understand Tamiflu™ release into the environment and evaluate associated risks
to human health and the ecosphere, a wide range of experts and organisations need to be actively
involved. Early action and holistic thinking about the issues is likely to lead to a more effective
pandemic flu strategy and help to ensure that humans and the environment are protected to the
greatest extent possible.
What is the workshop expected to achieve?
The workshop will assess the implications of Tamiflu™ release into the environment following mass
administration under pandemic flu conditions. This will be done by addressing the following sequence
of questions: