Unexpected, unplanned and undesirable events with GMOs that are released into the environment that could potentially lead to an increased risk to human health or the environment must be reported to the Human Environment and Transport Inspectorate (ILT). Only unexpected circumstances that occurred in studies in the Netherlands must be notified.
Unexpected circumstances are situations which could affect the risks to humans and the environment. This means that all unexpected circumstances that place the facts and considerations on which the risk assessment in the permit is based in a different light must be notified immediately. If an unexpected event can have an effect on elements of the application on which the conclusion of the risk analysis is based, this event must be notified. Unexpected circumstances can be adverse events, such as SAEs and SUSARs (Suspected Unexpected Serious Adverse Reactions ).
For more information, see examples of unexpected circumstances that must be notified.
By which deadline must notification be given?
Notification of all unexpected circumstances must be given ‘immediately’,i.e. as soon as the person responsible for notification has been informed of the situation, even if this person has not yet been able to fully ascertain the scale or consequences of the situation.
How should notification of adverse events be given?
The Gene Therapy Office must be notified of all adverse events occurred in the Netherlands. All unexpected circumstances must be notified by the legal entity, or by an authorized person such as Environmental Safety Officer, to the Human Environment and Transport Inspectorate (ILT). The notification must be submitted via the online form 'Notification unexpected circumstances' on the website of the Gene Therapy Office. All notifications are forwarded to ILT. For a notification by phone you can contact +31-88-4890000 during office hours.
What happens after notification?
Your notification of the incident will be handled by an inspector of ILT. This inspector will investigate after the notification whether the circumstances of the incident make it necessary to take follow-up measures and will always contact you.
Examples of unexpected circumstances that must be notified
Example 1.
Situation: A patient is treated with a replicating adenoviral vector. The GMO (Genetically Modified Organism
) is injected into the brain tumor and the wound is closed. After a week, the patient visits the general practitioner with a headache and feeling of pressure in the head, where there is fluid leaking from the site of administration.
Explanation: The GMO may still be present after a week in the brain and possibly around the injection site. Because fluid is released, there is a risk that the GMO is present in the fluid and that the environment is exposed to the GMO. This unexpected circumstance must be notified.
Example 2.
Situation: A patient is systemically treated with a GM-CSF (Granulocyte-macrophage colony-stimulating factor
)-producing genetically modified viral vector. During the holidays the patient falls and breaks a leg and some blood is lost. People at the scene helped the patient and possibly had been contact with the wound.
Explanation: There is likelihood that the GMO is systemic present in the bloodstream at the time of fracture. Therefore there is a risk that the GMO was present in the blood while leaking from the wound. The GMO may be released the environment and there is a potential environmental hazard. This unexpected circumstance must be notified.
Example 3.
Situation: A subject is vaccinated with a viral vector, in which parts of the influenza virus have been cloned. Sometime after vaccination the subject visits the doctor with flu-like symptoms such as high fever, sweating and coughing. The subject is sent home to recover.
Explanation: The viral vector can possibly be present in the body. The flu symptoms suggest an influenza virus infection. There is a risk of recombination between the viral vector and the influenza virus thereby creating recombinant influenza virus. This recombinant influenza virus may be the cause of the symptoms and infect others via coughing. There is a potential environmental hazard. This unforeseen circumstance must be notified.