Manufacturing A Gene Therapy With Patient Safety In Mind

Regulators worldwide have developed completely new and tailored directives to legislate for the safe manufacturing and use of these nascent and complex medicines. In Europe, they are classified as Advanced Therapy Medicinal Products (ATMP). In the USA, this is the remit of the Center for Biologics Evaluation and Research (FDA).

It is helpful to imagine the development of an advanced medicinal product more as an engineering endeavor. It then becomes apparent how each and every component entering the manufacturing would need to be defined, qualified and controlled at origin, in-process and at release. 

What exactly are those components? If we look at gene therapy, the medicinal product consists of or contains recombinant nucleic acid sequences or genetically modified organisms, viruses or cells. In all those cases the components are the starting materials and reagents (also called raw materials) used in the entire generation of the vectors, viruses, plasmids or genetically modified organisms/cells.

It is generally at this point, when the extent and complexity of starting materials is fully taken on board in the translational pipeline, that developers stumble in one crucial aspect: current Good Manufacturing Practices, or cGMP. In fact, to monitor and guarantee their safety, advanced medicines need to follow strict and specific cGMP regulations (which in Europe are detailed especially for ATMP), similarly to what applies to standard pharmaceuticals. And this is a major challenge. What for pharmaceuticals is a tried and tested industry reliant often on biochemical synthesis, for advanced medicines it is the engineering of living systems into a final active product.