Yes, it is possible to make changes after the permit has been issued. The changes to the clinical protocol should always be submitted to the CCMOCentral Committee on Research involving Human Subjects . More information.
Whether the changes should also be submitted to the Ministry of IenWMinistry of Infrastructure and Water Management depends on whether or not the clinical protocol is part of the IenW permit. If the clinical protocol is part of the IenW permit application, then changes must also be submitted to the Ministry of IenW. If the clinical protocol is not part of this permit, then one of the three procedures below can be followed in case the clinical protocol is changed.
1. If there are no implications for the environmental risk assessment that was carried out, then changes to the clinical protocol can be made without them having to be reported to the Ministry of IenW. However, if the changes are specifically referred to as a notification in accordance with Article 35 of the GMOGenetically Modified Organism
Regulations 2013, then you must follow the notification procedure of IenW.
2. If there are no significant implications for the environmental risk assessment that was carried out, then changes to the clinical protocol should also be submitted to the Ministry of IenW.
3. If there are significant implications for the environmental risk assessment that was carried out, then changes to the clinical protocol should also be submitted to the Ministry IenW.
If the GMOGenetically Modified Organism has been approved by the European Medicines Agency (EMAEuropean Medicines Agency ) and the European Commission for marketing authorisation, then a permit for the use specifically defined in the marketing authorisation is no longer needed. However, if a different type of use will be investigated in the clinical study besides the use defined in the marketing authorisation (such as a different indication, different dose or different patient population), a permit is still needed for the proposed work.
A sponsor cannot submit Part A of the application form. Only the legal entity who is ultimately responsible for the proposed work can apply for an IenWMinistry of Infrastructure and Water Management
permit. In most cases, this applicant is the Board of Directors (management) of the hospital (the institution) at which the study will be carried out. This legal entity (which is legally responsible) is therefore an institution or company and not a natural person. The person who signs Part A of the application form is authorised to do so on behalf of the legal entity.
Part B of the application will be assessed by the CCMOCentral Committee on Research involving Human Subjects and can be signed and submitted by the sponsor or others, if authorised by the sponsor.
Yes, it is possible to start the assessment of Part A of the application form before the full clinical trial application is submitted to the CCMOCentral Committee on Research involving Human Subjects and Ministry of Health, Welfare and Sport (VWSMinistry of Health, Welfare and Sport ). The assessments of Part A and Part B of the application form are separate procedures. Alternatively, the CCMO application (Part B) can be submitted prior to Part A. However, before starting the proposed work, all procedures must have been completed and approved. More information.
Yes, it is possible for foreign patients to participate in a clinical study in the Netherlands. The CCMOCentral Committee on Research involving Human Subjects reviews the ethical aspects of all medical or scientific research involving human subjects in the Netherlands, but the nationality of the trial subjects does not matter.
Approximately two weeks after the request for a preliminary meeting is filed, the Gene Therapy Office will suggest a number of dates on which the meeting can take place. A date for the meeting will be determined in consultation with the researcher. Preferred dates can be considered. More information.
Yes. A conference call from abroad is possible. You should request this in good time so that the equipment can be reserved. You must arrange the conference call yourself, including the dial-in numbers and the invitations to the participants. More information.
Part A - Biosafety aspects
No. If a single clinical protocol is to be implemented at various hospitals (multiple legal entities), all the hospitals must be issued a separate IenWMinistry of Infrastructure and Water Management permit. This is possible only if each hospital submits a separate permit application. However, these permit applications can be identical, with the exception of location-dependent data.
On the IenWMinistry of Infrastructure and Water Management permit application, the period within which the proposed work will take place must be specified. For this purpose, a final date can be indicated. The chosen final date will be included in the decision. It is possible to obtain an extension of the decision, but any extension procedure must be completed before the final date on the original decision has expired. Instead of a final date, the applicant can also indicate a maximum number of trial subjects. In that case, the final date of the decision coincides with the completion of the study with the final trial subject.
It regularly happens that biological specimens possibly containing GMOGenetically Modified Organism material (such as blood from patients) are tested at an institution that does not fall under the responsibility of the legal entity to whom the IenWMinistry of Infrastructure and Water Management permit was issued. In this case, the institute at which the specimens are tested should also apply for a permit for this work. This can be a permit for Contained Use (IG).
If biological specimens are tested in a laboratory abroad, this is not subject to Dutch legislation and a Dutch permit is not required. However, a permit is required for collecting, storing and transporting such specimens in the Netherlands.
The production of study material does not necessarily have to be included in the IenWMinistry of Infrastructure and Water Management permit application. Depending on the conditions, production in the Netherlands can also take place under a permit for Contained Use (CU). Production that takes place abroad is not included in a permit application in the Netherlands. However, the production characteristics are an important aspect of the permit application for the proposed study because this provides insight into the composition and quality of the GMOGenetically Modified Organism .
Besides submitting a permit application to the Ministry of IenWMinistry of Infrastructure and Water Management , the proposed activities must also be reported to the other Member States of the European Union by means of the SNIFSummary Notification Information Format (Summary Notification Information Format) form. More information.
If your permit application has been approved by IenM, you must submit a description of the proposed work (beschrijving van de voorgenomen werkzaamheden or BVWdescription of the proposed work ). The study can begin only after the BVW has been approved. More information.
Yes. If references are made to the literature (scientific or otherwise) on the application form, all the corresponding documents must be added to the dossier. If you refer to confidential information, which may be present in the Investigational Medicinal Product Dossier (IMPDInvestigational Medicinal Product Dossier ) or the clinical protocol, a public summary must be provided or the corresponding documents must be made public. Also see the information regarding confidential information.
A risk assessment is the product of the adverse effect and the likelihood of its occurrence. The adverse effect can be described as the effects on people and on the environment resulting from the use of the GMOGenetically Modified Organism , known as ‘hazard identification’. The environmental risk assessment must then specify the scenarios in which dissemination of the GMO in the environment can occur. The likelihood of actual dissemination must also be calculated. If relevant data are available, for example from biodistribution studies or shedding studies, these can be used to support the assessment.
If no data are available that can be used to support the environmental risk assessment, then a worst-case scenario can be used.
In a worst-case scenario it is assumed that the GMO will be disseminated into the environment and that third parties will be exposed to the organism. You can then describe the possible adverse effect that may occur in third parties as a result of the worst-case scenario. More information.
Part B - Patient-related aspects
The CCMOCentral Committee on Research involving Human Subjects should have the documents in its possession at least two weeks before the planned meeting. The meeting dates of the CCMO and the deadlines for submitting documents can be found on the CCMO website. When submitting documents to the Gene Therapy Office, add three additional days to allow time for forwarding the documents to the CCMO. More information.
Yes. While CCMOCentral Committee on Research involving Human Subjects assessment is pending, you can still submit the latest version of the protocol. Please indicate the amendments clearly. It is possible that this will cause the assessment to take somewhat longer, but this is more efficient than waiting for approval of the pending assessment and then submitting an amendment.
Ministry of Health, Welfare and Sport (VWSMinistry of Health, Welfare and Sport
c/o Medicines Evaluation Board (MEBMedicines Evaluation Board )
P.O. Box 8275
3503 RG Utrecht
Central Committee on Research Involving Human Subjects
PO Box 16302
2500 BH The Hague