Inspection of ‘first in human’ clinical trials
Clinical trials of medicinal products given to humans for the first time (first in human – FIH) must, as any other clinical trials, be approved by the Danish Medicines Agency before initiation. The Danish Medicines Agency inspects all FIH clinical trials and all trial sites, before the first trial subject is included.
The inspection takes place when the trial site is ready, i.e. after the initiation visit and after any unresolved issues related to the initiation visit have been clarified.
Focus on the safety aspects of inspection of FIH clinical trials
The main purpose of the early inspection is to make sure that the required safety aspects are in place before the first trial subject is treated with the new active substance. This means that the inspection focuses on:
- the physical surroundings and available facilities
- staff competencies and organisation
- agreements with other departments, e.g. intensive care units
- how it is ensured that patients are administered the medication correctly, e.g. staggered dosing, dosage levels, etc.
- safety procedures, e.g. committees.
Agreement with an intensive care unit
The Danish Medicines Agency believes that the physician responsible for a clinical trial (principal investigator) should make an agreement with an intensive care unit before an FIH clinical trial is initiated. This should ensure that acute emergency staff is available in case of serious adverse reactions or events related to the treatment.
The agreement must include information on the investigational medicinal product, the trial design (plus inclusion rate) and the date of expected start-up and completion of the clinical trial.
The intensive care unit must declare that it accepts that the clinical trial is carried out, and that it will inform the principal investigator if the intensive care unit predicts capacity problems so that the trial treatment can potentially be cancelled or postponed.
The agreement must specify that the principal investigator must inform the intensive care unit if any essential new knowledge emerges concerning the safety of the investigational medicinal product, or if any changes are made concerning the trial design or the duration of the clinical trial.
Resuscitation equipment
Trial subjects participating in FIH clinical trials are estimated to be at special risk of serious adverse reactions/incidents, including the risk of cardiac arrest. The principal investigator must therefore ensure easy access to the necessary emergency equipment. EMA’s guideline concerning FIH clinical trials (1) states as follows: Units should have immediate access to equipment and staff for resuscitating and stabilising individuals in an acute emergency. In the opinion of the Danish Medicines Agency, ‘immediate access’ means that resuscitation equipment, including defibrillators, must be available in the treatment room or the unit and that staff trained in the use of resuscitation equipment must be present during treatment of trial subjects.
(1): EMEA/CHMP/SWP/28367/07, GUIDELINE ON STRATEGIES TO IDENTIFY AND MITIGATE RISKS FOR FIRST-INHUMAN CLINICAL TRIALS WITH INVESTIGATIONAL MEDICINAL PRODUCTS