Methodological needs in the quality and safety characterisation of nanotechnology-based health products: priorities for method development and standardisation

Nanotechnology-based applications are providing innovative solutions in health technologies and the pharmaceutical field, responding to unmet clinical needs. However, suitable standardised methods need to be available for the assessment of quality and safety of these innovative products prior to their translation to the clinic and to monitor the quality of the drug when manufacturing processes are changed. The question arises which technological solutions are currently available within the scientific community to support the requested characterisation of nanotechnology-based products, and which methodological developments should be prioritized to support product developers in their regulatory assessment. To this end, the work here presented explored the state-of-the-art methods to identify methodological gaps associated with the preclinical characterisation of nanotechnology-based medicinal products and medical devices. The regulatory information needs expressed by regulatory authorities were extracted from the guidance documents released so far for nanotechnology-based health products and mapped against available methods thus allowing an analysis of methodological gaps and needs. In the first step, only standardised methods were considered, leading to the identification of methodological needs in five areas of characterisation, including: (i) surface properties, (ii) drug loading and release, (iii) kinetic properties in complex biological media, (iv) ADME (absorption, distribution, metabolism and elimination) parameters and (v) interaction with blood and the immune system. In the second step, a detailed gap analysis included analytical approaches in earlier stages of development, and standardised test methods from outside of the nanotechnology field that could address the identified areas of gaps. Based on this analysis, three categories of methodological needs were identified, including (i) method optimisation/adaptation to nanotechnological platforms, ii) method validation/standardisation and iii) method development for those areas where no technological solutions currently exist. The results of the analysis presented in this work aim to raise awareness within the scientific community on existing and emerging methodological needs, setting priorities for the development and standardisation of relevant analytical and toxicological methods allowing development of a robust testing strategy for nanotechnology-based health products.

HALAMODA KENZAOUI Blanka;  VANDEBRIEL Rob;  HOWARTH Alice;  SICCARDI Marco;  DAVID Christopher;  LIPTROTT Neill;  SANTIN Matteo;  BORGOS Sven Even;  BREMER Susanne;  CAPUTO Fanny; 

2021-07-07

ELSEVIER SCIENCE BV

JRC124411

0168-3659 (online),   

https://www.sciencedirect.com/science/article/pii/S0168365921003035,    https://publications.jrc.ec.europa.eu/repository/handle/JRC124411,   

10.1016/j.jconrel.2021.06.016 (online),