Fractionation is the process of separating plasma into proteins, which are then purified into final therapeutic products.
Quarantining of Collected Plasma
When plasma is received by BPL’s manufacturing facility in Elstree, UK, after collection and freezing, it is quarantined while quality checks are completed. The quarantine period also enables the removal of any plasma donation if new negative information becomes known about the donor’s health status. Only donations which have passed the rigorous safety and quality tests are released from quarantine for the manufacture of BPL products.
Plasma is fractionated in pools that contain several thousand individual plasma donations. Each of these pools is further tested for a range of potential viruses using Nucleic Acid Amplification Tests (NAT) to assure the quality of all BPL products.
Isolation of Proteins
The plasma fractionation process sequentially isolates different proteins from the pooled plasma. The most abundant proteins in human plasma are immunoglobulins and albumin, while coagulation factors are present only in trace amounts, which express high levels of biological activity. The multiple protein separation methods used to purify BPL products include precipitation, chromatography and filtration. These are optimised to accommodate the different chemistries of various plasma proteins, so that each can be identified and checked, and that the resulting products meet consistent and reproducible quality standards.
Each manufacturing process includes specific steps which are designed and validated to reduce any residual virus impurity. These steps include:
(a) chemical treatment with pH or solvent-detergent;
(b) thermal treatment by pasteurisation or terminal severe heat-treatment;
(c) physical partitioning by precipitation, chromatography or filtration.
BPL scientists ensure that these steps are compatible with the individual manufacturing process, so that virus reduction steps are effective but do not compromise the final product performance. Validation studies have confirmed that these steps can remove viruses with different generic characteristics (large or small; DNA or RNA; enveloped or non-enveloped). This knowledge also allows scientific assessment of the capability of the process to reduce any emerging new virus, if it were to enter the plasma supply chain.
Each product is subject to a number of steps to purify the active ingredient by manipulating the physicochemical properties of the active ingredients. Steps in purification include:
(a) Freezing and thawing
(c) Partitioning between different solvents
(d) Ion exchange chromatography
The purified proteins are formulated, so that the final sterile product is stable throughout its shelf-life. This important quality attribute assures optimum conditions for shipping and storage of the product by pharmacies, clinics and patients.
Our products are aseptic filled in to their final containers. Every bottle/vial is inspected before packing and serialisation in line with country specific requirements.
Every batch of each BPL product is tested against a rigorous specification which includes tests for composition, purity, function and safety. Samples are also sent to independent national testing laboratories (where mandated) to confirm compliance with specification. Products are only released to market after they have been shown to meet the specification requirements, as approved by national licensing authorities.