The production of the biotechnological active ingredient is divided into two phases:
Production of intermediate, Master Cell Banks, Working Cell Banks
The upstream phase begins with the production and storage of recombinant bacterial cells. These cells (master and working cell banks) must be stored at very low temperatures to preserve the recombinant strain for the entire product lifecycle.
These initial steps are followed by complex activities to grow, within bioreactors and under controlled conditions, the cell biomass until the recombinant human Nerve Growth Factor (rhNGF) production is achieved.
Purification of biotechnology derived active ingredients
In the downstream phase, the molecule is purified to enable it to be used as an active ingredient.
This entire production process takes several weeks to complete with the involvement of highly skilled technicians and biotechnologists.
Following the final formulation, sterilization and Fill & Finish in aseptic conditions performed by specialist subcontractors, the bulk sterile drug product returns to Dompé for final labeling and packaging, before marketing across the world including EU, US, China, Russia, Canada and Switzerland.
Importance of the cold chain
L’Aquila is a site of excellence also due to the design and creation of “cold rooms”. A key challenge in the production process is ensuring the active ingredients are maintained at very low temperatures to prevent damage.
● Certified by the Italian Medicines Agency (AIFA), cold rooms host our products at -20°C.
The development of a cold chain ensures that the product is distributed to the patient in controlled conditions. The cold chain features containers and pallets that we keep at -20°C. All systems within the cold chain are alarmed and provide an alert if a change in temperature is detected.
Innovative biotech production
In our Biotech production, we are adopting Single-Use disposable technologies. It features a single-use fermenter and centrifuge made of high-quality sterile plastic. The single use separator guarantee process contamination control and mitigate the cross-contamination risks.These technologies enable us to produce other molecules using the same process spaces and facilitate the management of the plant's multi-purpose approach.
The system doesn’t need sterilization and cleaning, reducing process cycle time, water, power and steam consumes.
How a protein is extracted
A genetic carrier (plasmid) containing the gene expressing the proNGF, precursor of the active ingredient rhNGF, is generated.
The plasmid is inserted in an E. coli bacterium.
The clone used to create the cell bank is generated from this bacterium.
The cell bank
Composed of vials containing bacteria that are genetically identical, the cell bank is stored in a repository that accommodates two liquid nitrogen (-173°C) cryogenic storage units and a freezer (-70°C). Each cryogenic unit may store up to 30,000 vials.
A portion of the cell bank is also stored off-site to guarantee business continuity in case of natural disasters.