The European Commission’s Enterprise and Industry Directorate-General has published new guidance clarifying what is meant by an “investigational medicinal product” in the context of a clinical trial. It also – and in substantially more detail – gives advice on the use in clinical studies of other medicines that do not fall under this definition.
To facilitate the conduct of clinical trials in the European Union, especially when they are carried out in more than one member state, there needs to be a common understanding of what constitutes an IMP, the guidance says.
Directive 2001/20/EC defines this in Article 2(d) as “a pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial, including products already with a marketing authorisation but used or assembled (formulated or packaged) in a way different from the authorised form, or when used for an unauthorised indication, or when used to gain further information about the authorised form”.
On this basis, and as long as the above requirements are met, reference products used as comparators in clinical trials should be regarded as IMPs, the guidance notes.
Products that do not meet the definition of IMPs in Directive 2001/20/EC may be supplied to participants in clinical trials and used in accordance with the protocol. For example, the guidance points out, some protocols call for the use of concomitant or rescue/escape medication for preventive, diagnostic or therapeutic purposes and/or to ensure that adequate medical care is provided to trial subjects.
These “non-investigational medicinal products” (NIMPs) may be supplied by a trial sponsor or investigator site that provides details of the NIMPs and their proposed use in the protocol while ensuring they are of the necessary quality for human use. The definition also extends to medicinal products without a marketing authorisation but prepared in accordance with a magistral formula (e.g., in a pharmacy from a medical prescription for an individual patient).
Quality, safety, efficacy
NIMPs with a marketing authorisation valid throughout the EU, or in one or more member state(s), are subject to the applicable requirements of Directive 2001/83/EC relating to the quality, safety and efficacy of medicines, the guidance observes. In terms of protecting trial subjects, the same level of quality and safety should be ensured as for IMPs used in a trial.
If the NIMP does not have a MA for the European Economic Area, the guidance adds, appropriate Good Manufacturing Practice (GMP) requirements should still apply and the sponsor should make sure the NIMPs are of suitable quality for the trial’s objective, “taking into account, among other things, the source of the raw materials and any repackaging”.