The sponsor of a clinical trial and the investigator shall ensure that the clinical trial is conducted in accordance with the protocol and with the principles of good clinical practice.
Without prejudice to any other provision of Union law or Commission guidelines, the sponsor and the investigator, when drawing up the protocol and when applying this Regulation and the protocol, shall also take appropriate account of the quality standards and the ICH guidelines on good clinical practice.
The Commission shall make publicly available the detailed ICH guidelines on good clinical practice referred to in the second paragraph.
In order to verify that the rights, safety and well-being of subjects are protected, that the reported data are reliable and robust, and that the conduct of the clinical trial is in compliance with the requirements of this Regulation, the sponsor shall adequately monitor the conduct of a clinical trial. The extent and nature of the monitoring shall be determined by the sponsor on the basis of an assessment that takes into consideration all characteristics of the clinical trial, including the following characteristics:
whether the clinical trial is a low-intervention clinical trial;
the objective and methodology of the clinical trial; and
the degree of deviation of the intervention from normal clinical practice.
The investigator shall be a medical doctor as defined in national law, or a person following a profession which is recognised in the Member State concerned as qualifying for an investigator because of the necessary scientific knowledge and experience in patient care.
Other individuals involved in conducting a clinical trial shall be suitably qualified by education, training and experience to perform their tasks.
The facilities where the clinical trial is to be conducted shall be suitable for the conduct of the clinical trial in compliance with the requirements of this Regulation.
1.Investigational medicinal products shall be traceable. They shall be stored, returned and/or destroyed as appropriate and proportionate to ensure the safety of the subject and the reliability and robustness of the data generated in the clinical trial, in particular, taking into account whether the investigational medicinal product is an authorised investigational medicinal product, and whether the clinical trial is a low-intervention clinical trial.
The first subparagraph shall also apply to unauthorised auxiliary medicinal products.
2.The relevant information regarding the traceability, storage, return and destruction of medicinal products referred to in paragraph 1 shall be contained in the application dossier.
1.The sponsor shall notify the Member States concerned about a serious breach of this Regulation or of the version of the protocol applicable at the time of the breach through the EU portal without undue delay but not later than seven days of becoming aware of that breach.
2.For the purposes of this Article, a ‘serious breach’ means a breach likely to affect to a significant degree the safety and rights of a subject or the reliability and robustness of the data generated in the clinical trial.
1.The sponsor shall notify the Member States concerned through the EU portal of all unexpected events which affect the benefit-risk balance of the clinical trial, but are not suspected unexpected serious adverse reactions as referred to in Article 42. That notification shall be made without undue delay but no later than 15 days from the date the sponsor became aware of this event.
2.The sponsor shall submit to the Member States concerned, through the EU portal, all inspection reports of third country authorities concerning the clinical trial. When requested by a Member State concerned, the sponsor shall submit a translation of the report or of its summary in an official language of the Union indicated in the request.
1.Where an unexpected event is likely to seriously affect the benefit-risk balance, the sponsor and the investigator shall take appropriate urgent safety measures to protect the subjects.
2.The sponsor shall notify the Member States concerned, through the EU portal, of the event and the measures taken.
That notification shall be made without undue delay but no later than seven days from the date the measures have been taken.
3.This Article is without prejudice to Chapters III and VII.
1.The sponsor shall provide the investigator with the investigator's brochure.
2.The investigator's brochure shall be updated where new and relevant safety information becomes available, and shall be reviewed by the sponsor at least once per year.
1.All clinical trial information shall be recorded, processed, handled, and stored by the sponsor or investigator, as applicable, in such a way that it can be accurately reported, interpreted and verified while the confidentiality of records and the personal data of the subjects remain protected in accordance with the applicable law on personal data protection.
2.Appropriate technical and organisational measures shall be implemented to protect information and personal data processed against unauthorised or unlawful access, disclosure, dissemination, alteration, or destruction or accidental loss, in particular where the processing involves the transmission over a network.
The sponsor and the investigator shall keep a clinical trial master file. The clinical trial master file shall at all times contain the essential documents relating to that clinical trial which allow verification of the conduct of a clinical trial and the quality of the data generated, taking into account all characteristics of the clinical trial, including in particular whether the clinical trial is a low-intervention clinical trial. It shall be readily available, and directly accessible upon request, to the Member States.
The clinical trial master file kept by the investigator and that kept by the sponsor may have a different content if this is justified by the different nature of the responsibilities of the investigator and the sponsor.
Unless other Union law requires archiving for a longer period, the sponsor and the investigator shall archive the content of the clinical trial master file for at least 25 years after the end of the clinical trial. However, the medical files of subjects shall be archived in accordance with national law.
The content of the clinical trial master file shall be archived in a way that ensures that it is readily available and accessible, upon request, to the competent authorities.
Any transfer of ownership of the content of the clinical trial master file shall be documented. The new owner shall assume the responsibilities set out in this Article.
The sponsor shall appoint individuals within its organisation to be responsible for archives. Access to archives shall be restricted to those individuals.
The media used to archive the content of the clinical trial master file shall be such that the content remains complete and legible throughout the period referred to in the first paragraph.
Any alteration to the content of the clinical trial master file shall be traceable.
1.Only authorised auxiliary medicinal products may be used in a clinical trial.
2.Paragraph 1 shall not apply where no authorised auxiliary medicinal product is available in the Union or where the sponsor cannot reasonably be expected to use an authorised auxiliary medicinal product. A justification to this effect shall be included in the protocol.
3.Member States shall ensure that unauthorised auxiliary medicinal products may enter their territories for the purpose of their use in a clinical trial in accordance with paragraph 2.