QP Expertise Facilitates EU Clinical Trials with Non-Investigational Medicinal Products (NIMPs)
Investigational medicinal products are well understood and defined within the European Union under Directive 2001/20/EC. However, clinical trials today often involve other products that, although used in the trial, are not the object of investigation. These medicinal products do not fall within the definition of investigational medicinal products and are called “non-investigational medicinal products” (NIMPs). They are supplied to aid the trial. For example, a rescue medication where a phase III clinical trial is trying to assess the efficacy of a new anti-neoplastic IMP. All patients receive a corticoid /antihistamine treatment in order to minimise the appearance of expected adverse reactions.
The importation and release of these medicinal products is not well defined universally across the EU, when they are imported from outside the EU. EU/UK legislation requires that any importation and supply of products that do not hold a license in the EU must be supplied in the UK under ‘’special’’ /unlicensed arrangements, which has very specific stipulations for number of doses and very specific requests from clinicians.
In most circumstances, it is expected that a NIMP is sourced and supplied by the Sponsor within the EU. However, this is not always the case.
Our client, a leading pharmaceutical company was planning to conduct a Phase III study requiring adjunctive therapies for anti-depressant disorders in the EU. The preferred distribution strategy was to import all supplies into the UK initially, and then supply the various competent authorities throughout the EU. This US-based Sponsor incorrectly assumed that NIMPs already sourced in the US could be released in the EU without further documentation.
Understanding the legislation and liaising with the competent authority early in the planning stage were key factors for success with this trial. Fisher Clinical Services stipulated that:
- Importation of non-EU NIMPs is not covered by any importation licence in the EU
- The legislation surrounding the importation and use of NIMPs is variable across the EU
- A strategy of supply would have to be agreed in advance as there is no QP release of NIMPs
Fisher Clinical Services Horsham convened a team of experts to conduct a technical assessment of the trial requirements with particular focus on the complexities related to the importation and exportation of NIMPs in the EU. This team comprised of Qualified Persons (QPs) and other senior clinical operations team members. Their extensive knowledge and expertise resulted in a quick and efficient technical assessment of what was needed to facilitate the requirements of this clinical trial.
The options for importation and release were assessed by the technical group.
A systematic elimination of importation and release routes were discussed.
- The product was not an IMP. The Manufacturing Import Authorisation (MIA) IMP license could not be used.
- The MIA for commercial products could not be used either, as the Product license was not held by Fisher Clinical Services.
- The specials route could only be used with specific requirements such as limited quantities and only by unsolicited requests from clinicians. Specials legislation is specific to the UK and provides a method for otherwise unlicensed medicines to be supplied to patients under very specific circumstances.
- The only route was to discuss the specific legislative requirements with the UK competent authority. Fisher Clinical Services was best positioned to leverage technical expertise and contacts within the competent authority to agree a solution. A novel route was explored and successful agreement with the competent authority achieved. This demonstrated a ‘thinking outside the box’ mentality, and an agreement to apply a flexible and compliant approach to this issue. It was agreed that the specials license would be used, but outside the usual method. The CT Approval would be used in place of Clinician of US sourced NIMPs.
The Sponsor’s concerns as to how the NIMPs could be released were alleviated. Fisher Clinical Services Horsham showed drive and commitment in resolving this issue. The Horsham team:
- Opened discussion with the UK competent authority.
- Agreed a novel proposed importation/exportation method with the UK competent authority. Resolved the importation issue using a non-standard view on the ‘’specials’’ process.
- Provided timely feedback and communication to the Sponsor on progress with the UK competent authority.
- Provided overall management of the importation and supply of product, leveraging the expertise of the QP group onsite.
- Submitted all relevant documentation and details facilitating importation and release of NIMPs.
- Provided QP overview and release of product OTIF (on-time and in-full) of all NIMPs. All products were supplied to clinical sites with no delay to the trial.
Without the expertise of the QP services at Fisher Clinical Services Horsham, the Sponsor may have had to re-source the NIMPs within the EU. This would have taken a lot of time and effort, not to mention expense. Technical expertise was at its best with all parties working together to ensure adequate supplies were ready for delivery as per protocol guidelines
- Agreement with competent authority on how to handle NIMPs in the EU.
- Clear communication between the Sponsor, Fisher Clinical Services and the competent authority.
- Effective on-going management and control of the entire investigation.
- Supply of all NIMPs compliantly and efficiently, OTIF to investigator sites throughout the EU.
- Savings achieved as the Sponsor did not have to re-source NIMPs within the EU
Fisher Clinical Services offers comprehensive services for the preparation of QP Declarations and performs supporting audits that may be required. All Fisher Clinical Services QPs are trained as ISO Lead Auditors and have extensive experience in auditing facilities across the world.