Scale-up Challenge

A European Consortium composed of industrial and academic partners aims to optimize and further develop a novel formulation containing an enzyme used for the therapy of Fabry Disease, and establish its production at industrial scale. Fabry disease is caused by a deficiency in enzyme α-galactosidase A (GLA), which provokes the accumulation of glycosphingolipids leading to multiple organ pathology. This new formulation, obtained with the DELOS platform, is based on enzyme-loaded nanoliposomes that enhance the stability and efficacy of the enzyme. This further development requires scaling-up the manufacturing process and implement it for regulatory pre-clinical testing in order to consolidate the preclinical package.

Our Proposal

Our scientists and engineers proposed to apply a Quality by Design (QbD) approach to optimize the nanoformulation and to develop a robust process for the preparation of GLA-loaded nanoliposomes with DELOS platform, adequate for regulatory preclinical testing.

our developed

Under the leadership of Nanomol Technologies, a scale-up work-package has been implemented and the following goals have been achieved:

  1. Critical Quality Attributes (CQAs) of the nano-GLA formulation, were defined and oriented to a quality control strategy.
  2. Risk Analysis and Design of Experiments were performed in order to evaluate the impact of Critical Process Parameters (CPPs) and Critical Materials Atributes (CMAs) on each CQA.
  3. The formulation was optimized, achieving a 10-fold increase in protein concentration.
  4. A design space was stablished in which the product obtained by DELOS fulfils all required quality specifications

Benefits obtained


A nanomedicine prototype suitable for regulatory in vivo testing has been developed and demonstrated following the requirements of the pharmaceutical industry and the european regulatory authorities.


The formulation was successfully scaled up from the lab scale until pilot plant (liter scale).


High degree of process control and understanding were achieved by implementing QbD methodology.


Robust production of GLA nanoformulation has been set in order to produce batches for regulatory preclinical package and enabling future clinical testing.