Division 4.1 Specific requirements for all advanced therapy medicinal productsF1F2

The requirements of Part I, Module 4 of this Annex on the pharmacological and toxicological testing of medicinal products may not always be appropriate due to unique and diverse structural and biological properties of advanced therapy medicinal products. The technical requirements in sections 4.1, 4.2 and 4.3 below explain how the requirements in Part I of this Annex apply to advanced therapy medicinal products. Where appropriate and taking into account the specificities of advanced therapy medicinal products, additional requirements have been set.

The rationale for the non-clinical development and the criteria used to choose the relevant species and models ( in vitro and in vivo ) shall be discussed and justified in the non-clinical overview. The chosen animal model(s) may include immuno-compromised, knockout, humanised or transgenic animals. The use of homologous models (e.g. mouse cells analysed in mice) or disease mimicking models shall be considered, especially for immunogenicity and immunotoxicity studies.

In addition to the requirements of Part I, the safety, suitability and biocompatibility of all structural components (such as matrices, scaffolds and devices) and any additional substances (such as cellular products, biomolecules, biomaterials, and chemical substances), which are present in the finished product, shall be provided. Their physical, mechanical, chemical and biological properties shall be taken into account.