Information about the assessment

Appendix XV of the regulation contains a detailed list of the information to be submitted with an application for authorisation of clinical investigation of medical devices, including a detailed description of the information that must be included in the investigation plan and the investigator’s brochure.

The Danish Medicines Agency starts its validation promptly upon receipt of the application and has up to 15 calendar days to validate the application.

Two elements are assessed in the validation phase:

• Whether the investigation falls within the scope of the regulation by establishing whether the application involves a medical device and whether the clinical investigation is subject to authorisation by the Danish Medicines Agency.

• Whether all the required information has been supplied, in which case the application is considered complete and the assessment phase can start.

If the application is considered valid and complete, it is assigned a VALIDATION DATE.

If information is missing, the sponsor will on day 15 at the latest receive a letter from the Danish Medicines Agency detailing that the application is either invalid or that it falls outside the scope of the regulation. The sponsor hereafter has up to 30 calendar days to resubmit the application. All of the missing elements must be submitted in one single email to both the Danish Medicines Agency and the Medical Research Ethics Committees.

If additional or new material is submitted, the Danish Medicines Agency has 10 days to assess the completeness of the re-submitted application.

Provided the missing documents or information has been submitted, the sponsor will receive a letter detailing that the application is valid and complete and that the application is assigned a validation date. The validation date marks the start of the assessment.

Alternatively, it may be determined, even after the sponsor has had the opportunity to submit additional information, that the application is deemed invalid and therefore void.

The Danish Medicines Agency has 45 days after the validation date to assess the application and decide in the matter.

During the assessment period, the sponsor can expect to receive additional questions from the Danish Medicines Agency and the Medical Research Ethics Committees. The time limit of 45 days for assessment of the application may, pursuant to the regulation, be suspended from the date when the Danish Medicines Agency requests the sponsor to submit additional information until receipt of the additional information.

The reply to additional questions must be submitted as a single, complete answer by email simultaneously to both the Danish Medicines Agency and the Medical Research Ethics Committees. All questions must be sufficiently answered.

Once the sponsor has submitted its additional information, the time limit for assessment of 45 calendar days is no longer suspended. Additional information could still be needed, in which case the time limit of 45 days is not suspended any further.

A clinical investigation may commence when the Danish Medicines Agency has authorised the investigation with due account be taken to the Medical Research Ethics Committees’ opinion. The Danish Medicines Agency must decide on the authorisation within 45 days of the validation date for an application for authorisation of clinical investigation. The assessment time may often be longer because the time limit for assessment is suspended while the sponsor is submitting additional information. 

The Danish Medicines Agency may require as part of the authorisation that an annual report on the safety of subjects be submitted annually throughout the investigation period. The annual report must include a list of all serious adverse events (SAEs) that have occurred during the investigation period in Denmark and abroad as well as an assessment of the risks and benefits of the investigational device. The annual safety report must include a conclusion regarding the safety of the subjects.

The Danish Medicines Agency notes the following with respect to implants and medical devices that may potentially involve a systemic absorption of substances or pose other risks to pregnancy: The investigation plan must clearly describe that it has been ensured that women of childbearing potential are not pregnant prior to participating in the investigation (negative pregnancy test prior to inclusion in the investigation) and that adequate contraception is used during the investigation. The sponsor is also requested to consider for how long contraception must be used during or after the investigation, just as the duration of the contraception requirement must be clearly justified.

The Danish Medicines Agency considers the following contraceptive methods to be safe in connection with clinical investigation: intrauterine devices, hormonal contraceptives such as contraceptive pills, implants, transdermal patches, hormonal vaginal devices and injections with prolonged release. It is accepted in certain cases to include subjects having a sterilised permanent partner or subjects using double barrier contraceptive methods. However, this should be explicitly justified in special circumstances arising from the design of the investigation, the device and/or patient population. Double barrier methods of contraception mean a condom combined with a diaphragm.

Sterilised or infertile subjects are exempt from the requirement to use contraception. In order to be considered sterilised or infertile, subjects must generally have undergone surgical sterilisation (vasectomy/bilateral tubectomy, hysterectomy and bilateral ovariectomy) or be postmenopausal defined as 12 months or more with no menses prior to enrolment.

For some individuals or special populations, there may be arguments against using the above-mentioned methods. Examples include seriously ill, hospitalised patients or fertile children who are not sexually active. In such cases, any derogation from a requirement for contraception may be acceptable when justified in special circumstances arising from the design of the investigation, the device and/or patient population