How are biopharmaceuticals produced in bioreactors? What makes them different from traditional drugs made via chemical synthesis? What is the full technological route for producing a batch of biopharmaceutical products based on allogeneic MSCs?

Biopharmaceuticals are products in which active pharmaceutical ingredients (APIs) are living cells or substances produced by these cells in industrial culture bioreactors. Their manufacture harnesses natural processes of biosynthesis and cellular biochemistry, producing biologically active substances as a result. Such substances include therapeutic antibodies, hormones, growth factors – active pharmaceutical ingredients of biopharmaceuticals. Biopharmaceuticals are far more challenging to develop and manufacture than chemically synthesised pharmaceuticals.

Biotechnological production – due to the natural variability inherent to living organisms and the naturally occurring errors (mutations) – requires much greater in-process control (IPC) than traditional pharmaceutical production. Maintaining microbiological purity is particularly crucial, as it is impossible to perform terminal sterilisation on the product. The microbiological purity is ensured by a number of advanced technological solutions, as well as compliance with the Standard Operating Procedures (SOPs).

Bioceltix pharmaceutical manufacturing process involves isolation of primary stem cells from an eligible, healthy donor, subsequent purification through in vitro culture, and finally, cryopreservation of the mesenchymal stem cells, ready to be administered immediately after thawing without any loss of therapeutic potential.

How do we produce a batch of a medicinal product based on allogeneic stem cells and intended for veterinary use? What does the technological route look like at Bioceltix?

The route consists of nine stages:

1. Assessment of the adipose tissue donating animal through a panel of tests (recommended for allogeneic stem cell production by the EMA).
2. Pharmaceutical-grade isolation and in vitro culture of mesenchymal stem cells.
3. In-process quality control (IPQC) using advanced analytical methods.
4. Controlled cryopreservation of the finished product.
5. Sterility testing in accordance the guidelines on sterile medicinal products.
6. Release of the medicinal product batch by a qualified person.
7. Storage and shipment of the biopharmaceutical in compliance with GDP (Good Distribution Practice).
8. Pharmacovigilance.
9. Continuous product quality improvement – applying new solutions to production and quality control.