(51) The information generated in a clinical trial should be recorded, handled and stored adequately for the purpose
of ensuring subject rights and safety, the robustness and reliability of the data generated in the clinical trial, accu
rate reporting and interpretation, effective monitoring by the sponsor and effective inspection by Member States.
(52) In order to be able to demonstrate compliance with the protocol and with this Regulation, a clinical trial master
file, containing relevant documentation to allow effective supervision (monitoring by the sponsor and inspection
by Member States), should be kept by the sponsor and by the investigator. The clinical trial master file should be
archived appropriately to allow for supervision after the clinical trial has ended.
(53) Where there are problems with respect to the availability of authorised auxiliary medicinal products, unauthorised
auxiliary medicinal products may be used in a clinical trial in justified cases. The price of the authorised auxiliary
medicinal product should not be considered as having an effect on the availability of such medicinal products.
(54) Medicinal products intended for research and development trials fall outside the scope of Directive 2001/83/EC
of the European Parliament and of the Council (
1
). Such medicinal products include medicinal products used in
the context of a clinical trial. They should be covered by specific rules taking account of their peculiarities. In
establishing these rules, a distinction should be made between investigational medicinal products (the tested
product and its reference products, including placebos) and auxiliary medicinal products (medicinal products used
in the context of a clinical trial but not as investigational medicinal products), such as medicinal products used
for background treatment, challenge agents, rescue medication, or used to assess end-points in a clinical trial.
Auxiliary medicinal products should not include concomitant medications, that is medications unrelated to the
clinical trial and not relevant for the design of the clinical trial.
(55) In order to ensure subject safety and the reliability and robustness of data generated in a clinical trial, and in
order to allow for the distribution of investigational and auxiliary medicinal products to clinical trial sites
throughout the Union, rules on the manufacturing and import of both investigational and auxiliary medicinal
products should be established. As is already the case for Directive 2001/20/EC, those rules should reflect the
existing rules of good manufacturing practices for products covered by Directive 2001/83/EC. In some specific
cases, it should be possible to allow deviations from those rules in order to facilitate the conduct of a clinical
trial. Therefore, the applicable rules should allow for some flexibility, provided that subject safety, as well as relia
bility and robustness of the data generated in the clinical trial are not compromised.
(56) The requirement to hold an authorisation for manufacture or import of investigational medicinal products should
not apply to the preparation of investigational radiopharmaceuticals from radionuclide generators, kits or radio
nuclide precursors in accordance with the manufacturer's instructions for use in hospitals, health centres or
clinics taking part in the same clinical trial in the same Member State.
(57) Investigational and auxiliary medicinal products should be appropriately labelled in order to ensure subject safety
and the reliability and robustness of data generated in clinical trials, and in order to allow for the distribution of
those products to clinical trial sites throughout the Union. The rules for labelling should be adapted to the risks
to subject safety and the reliability and robustness of data generated in clinical trials. Where the investigational or
auxiliary medicinal product have already been placed on the market as an authorised medicinal product in
accordance with Directive 2001/83/EC and Regulation (EC) No 726/2004 of the European Parliament and of the
Council (
2
), as a general rule no additional labelling should be required for clinical trials that do not involve the
blinding of the label. Moreover, there are specific products, such as radiopharmaceuticals used as diagnostic inves
tigational medicinal product, where the general rules on labelling are inappropriate in view of the very controlled
setting of the use of radiopharmaceuticals in clinical trials.
(58) In order to ensure clear responsibilities, the concept of a ‘sponsor’ of a clinical trial, in line with international
guidelines, was introduced by Directive 2001/20/EC. This concept should be upheld.
(59) In practice, there may be loose, informal networks of researchers or research institutions which jointly conduct a
clinical trial. Those networks should be able to be co-sponsors of a clinical trial. In order not to weaken the
27.5.2014 L 158/7 Official Journal of the European Union
EN
1
) Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal
products for human use (OJ L 311, 28.11.2001, p. 67).
(
2
) Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for
the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency
(OJ L 136, 30.4.2004, p. 1.)