The goal of the nTRACK project was to develop cell-tracking methodology based on an innovative, highly sensitive multimodal nano-imaging agent. Cell-based therapy forms a promising approach to treat various diseases for which conventional therapies are ineffective. However, the prediction of the success or failure of cell therapy is challenged by the current lack of methods to track the bio distribution and fate of the transplanted cells. The nTRACK nano-imaging agent was developed to allow the visualisation and longitudinal monitoring of the transplanted stem cells in real time.

Consortium

The project partners in a consortium led by Leitat Technological Center were: Bar Ilan University, Pluristem Therapeutics, University Medical Center of Johannes Gutenberg University Mainz, MJR PharmJet, BET Solutions, National Centre for Scientific Research “Demokritos”, Vall d’Hebron Research Institute, Vivotecnia Research, RIVM, Asphalion, and Cambridge Nanomaterials Technology.

Role of RIVM

Because of the innovative nature of a nanotechnology-based imaging agent and its combined use within an advanced cell therapy, the regulatory classification and appropriate regulatory pathway were not straightforward. RIVM’s role was to ensure that the regulatory aspects were taken into account at an early stage of development. In this project, we followed the regulatory process of the nTRACK nano-imaging agent marketed as a stand-alone product. We translated learned lessons from the project into a general recommendation for both developers and policymakers. In addition, we identified potential gaps and ambiguities in the relevant European regulatory frameworks, which we discussed with developers, national competent authorities and policymakers.  
RIVM's  Centre for Health Protection was involved in the nTRACK project.

Results

As part of this investigation on regulatory context of the nTRACK nano-imaging agent as a stand-alone product, the consortium partners and diverse international experts were consulted. Information was used from the consultation with the EMA-ITF and the two national competent authorities and an online international workshop was organized to obtain input from external parties, including representatives of relevant regulatory bodies, cell therapy developers, and cell imaging experts. 

The major challenge was to identify the appropriate regulatory classification of the nTRACK nano-imaging agent as a stand-alone product. The views among experts and authorities on the classification of this product diverge. This makes it difficult to determine the regulatory pathway to follow as the classification of a product determines what kind of safety information requirements are necessary, which quality management systems are involved and the approval procedures to follow at a specific authority.

From the consultation with the experts and authorities it became apparent that regardless the classification, appropriate quality and preclinical safety information for the nano-imaging agent is required, which include nano-specific information, such as the characteristics of the nanoparticles. However, standard methods for regulatory preclinical quality and safety studies with nanomaterials do not always exist. 

We recommend that there should be regulatory guidance and standards for these types of products. Not only for the classification, but also to identify the quality and safety requirements of such novel products. Also exchanging information between developers and regulatory authorities helps to improve the regulatory process and to reduce the knowledge gap and is therefore highly recommended.  
 

Funding

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 761031.