Guidance
Clinical trials: Non-investigational medicinal products
Guidance on using non-investigational medicinal products in a clinical trial.
Change of https://www.gov.uk/guidance/clinical-trials-non-investigational-medicinal-products
Change description : 2025-10-01 13:51:00: Major update to guidance and diagram attachments [Guidance and regulation]
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Guidance on using non-investigational medicinal products in a clinical trial.
This guidance accompanies the Medicines for Human Use (Clinical Trials) Regulations 2004 (“the Clinical Trials Regulations”), as amended by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025.
These amendments come into force on 28 April 2026.
Until this date, this guidance is in draft and should only be used to support sponsors in preparing for the implementation of the new regulations. Please see Clinical trials for medicines: apply for authorisation in the UK and Clinical trials for medicines: manage your authorisation, report safety issues for the guidance that should be followed prior to 28 April 2026.
The following guidance accompanies the Medicines for Human Use (Clinical Trials) Regulations 2004 (“the Clinical Trials Regulations”), as amended by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2025. These amendments come into force on 28 April 2026. For assistance in determining whether a clinical trial is within the scope of these Regulations, see the Is it a clinical trial of a medicinal product? algorithm (please note that this document will be updated in due course).algorithm.
Part 2 of Schedule 1 to the Clinical Trials Regulations requires that the investigator and sponsor (and any individual or organisation that the sponsor delegates trial-related activities to) have regard to all relevant guidance with respect to commencing and conducting a clinical trial. Investigators and sponsors must, therefore, ensure that they are fully aware of the information within this guidance and act accordingly to achieve and maintain regulatory compliance.
Per regulation 2 of the Clinical Trials Regulations, a non-investigational medicinal product (NIMP) is a medicinal product used or to be used in a clinical trial, as described in the protocol, but not as an investigational medicinal product (IMP). For the purpose of the above definition:
Non-medicinal products are products that are used or to be used in a clinical trial in the same way as an NIMP but that do not meet the definition of a medicinal product.product (e.g. use of pollen or house dust in a skin prick test).
This guidance also applies to these non-medicinal products, unless otherwise specified.
In most cases, NIMPs used in a clinical trial should hold a marketing authorisation. Where an authorised NIMP does not exist or where the sponsor cannot be reasonably expected to use it, the sponsor may use an unauthorised NIMP, ensuring that clear justification for this is given in the trial protocol.
Acceptable justifications for using an unauthorised NIMP include where there are issues with the availability of the authorised product (not including issues relating to the price) and where the NIMP does not have a marketing authorisation but is prepared in accordance with a magistral or official formula.
Rescue medications (or escape medications) are NIMPs identified in the protocol as medicinal products that may be administered to patients:
Examples of this type of NIMP include:
Challenge agents are NIMPs (or sometimes non-medicinal products) given to trial participants to produce a physiological response that is necessary before the pharmacological action of the IMP can be assessed. This would include, for example, the product used in a skin prick test used to identify allergic responses to specific allergens (as the NIMP is being administered to modify a physiological function by exerting an immunological action).
Examples of this type of NIMP include:
NIMPs can be given to a trial participant as a tool to assess a relevant clinical trial endpoint. In these cases, the product is not being tested or used as a reference in the clinical trial.
Examples of this type of NIMP include:
This type of NIMP is administered to each of the clinical trial participants, regardless of randomisation group, either to treat the indication which is the object of the study or as part of the standard of care treatment for a condition which is not the indication under investigation but is relevant for the clinical trial design.
The IMP for the clinical trial is given in addition to the background treatment. The protocol may require that the IMP plus the background treatment is compared to an active comparator, or to placebo plus background treatment.
Where the current standard of care treatment is given as a background treatment, either:
The nature of the background medicine(s) will be specified in the protocol e.g. as the standard treatment given according to local clinical practice, by the name of active substances or medicinal products prescribed depending on patient needs and according to the doctor’s judgement.
The standard care medicine(s) for a specific indication (recognised standard of care), or a component of the standard care for a particular medical indication, is based on national and international consensus.
Please note that:
Examples of this type of NIMP include:
In contrast, an example of when the current standard of care treatment is not considered to be background therapy is:
Per Schedule 3 of the Clinical Trials Regulations, an application for clinical trial approval must include a dossier that contains details of the quality of any NIMP. For further guidance, please refer to the guidance on Documents required for an application for clinical trial approval. Please note that although this guidance refers to IMPs, it also applies to NIMPs. A list of NIMPs proposed for use in the trial should also be included in the cover letter.
For NIMPs that are both authorised and unmodified (i.e. packaged and labelled according to their authorisation), a simplified dossier is accepted, per the guidance on Cross-referencing and simplified investigational medicinal product dossiers.
Non-medicinal products do not necessarily require their own dossier but must, as a minimum, be listed in the cover letter and included in an IMP dossier with information about their properties, labelling, manufacture, stability and safety controls, as appropriate to the product.
Per regulation 45A of the Clinical Trials Regulations, all NIMPs (regardless of authorisation status) must be manufactured or assembled in accordance with the principles and guidelines for Good Manufacturing Practice that apply under the Medicines for Clinical Trials Regulations or the Human Medicines Regulations 2012. Evidence of this (e.g. a manufacturer’s authorisation for the site of manufacture) should be included in the application for clinical trial approval.
The manufacture of non-medicinal products must be shown to comply with the safety standards applicable to that product. It may also be necessary to demonstrate compliance with relevant safety standards applicable to medicines suitable for use in humans.
Per regulation 46A of the Clinical Trials Regulations, NIMPs used in a clinical trial are subject to the same labelling requirements as IMPs (which are described in regulation 46 of the Clinical Trials Regulations.
The exception to this is that there are different labelling requirements where an authorised IMP is to be exclusively administered in a hospital or health centre taking part in the clinical trial, but this is not the case for authorised NIMPs.
As the majority of NIMPs are expected to be authorised medicinal products, used unmodified, they should in most cases be labelled in accordance with the existing UK requirements for prescribed medicines dispensed by pharmacies set out in Part 13 of the Human Medicines Regulations 2012.
Detailed guidance on labelling requirements for non-investigational medicinal products used in a clinical trial can be found in Labelling for products used in clinical trials.
See the Guidance on the collection, verification and reporting of safety events in clinical trials of an investigational medicinal product for:
Major update to guidance and diagram attachments
Link to feedback questionnaire removed following closure of questionnaire.
First published.
2026-03-09 09:00
Clarified that non-medicinal products should be labelled in the same way as unlicensed NIMPs. Added guidance on determining whether a product is an NIMP or a non-medicinal product. Clarified requirements for including information about non-medicinal products in the clinical trial application. Included additional guidance on providing evidence that NIMPs were manufactured according to GMP principles. Included guidance on providing evidence that non-medicinal products were manufactured according applicable safety standards. Clarified labelling expectations for non-medicinal products
2025-10-01 13:51
Major update to guidance and diagram attachments
2025-08-21 14:54
Link to feedback questionnaire removed following closure of questionnaire.
2025-06-25 10:07
First published.