A novel core fractionation process of human plasma by expanded bed adsorption chromatography

Lihme, Allan; Hansen, Marie Bendix; Andersen, Inga Vaarst; Burnouf, Thierry

doi:10.1016/j.ab.2009.12.002

Cited by 26 publications

(23 citation statements)

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“…Plasma was directly applied to the first column and 5 proteins were sequentially separated, including FVIII. They also obtained 50% of FVIII recovery (Lihme et al 2010). The vitamin K-dependent coagulation factors are FVIII natural activators, therefore traces present in the cryoprecipitate are separated early in the purification processes, either by precipitation or adsorption in aluminum hydroxide (Burnouf 2007).…”

Section: Resultsmentioning

confidence: 95%

“…5c the purification eliminates the centrifugation steps and the process takes place at room temperature (20°C). Processes that include subsequent anion exchange or affinity chromatography using monoclonal antibody (mAb) allow recoveries of 30-50% from cryoprecipitate and 10-20% from plasma (Lihme et al 2010). Recently it was described an elegant purification method using expanded bed adsorption chromatography.…”

Section: Resultsmentioning

confidence: 99%

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Purification of coagulation factor VIII using chromatographic methods. Direct chromatography of plasma in anion exchange resins

et al. 2010

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Coagulation factor VIII (FVIII) concentrates are used in the treatment of patients with Hemophilia A. Human FVIII was purified directly from plasma using anion exchange chromatography followed by gel filtration. Three Q-Sepharose resins were tested, resulting in 40% recovery of FVIII activity using Q-Sepharose XL resin, about 80% using Q-Sepharose Fast Flow and 70% using the Q-Sepharose Big Beads. The vitamin K-dependent coagulation factors co-eluted with FVIII from the anion exchange columns. In the second step of purification, when Sepharose 6FF was used, 70% of FVIII activity was recovered free from vitamin K-dependent factors.

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Section: Resultsmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Purification of coagulation factor VIII using chromatographic methods. Direct chromatography of plasma in anion exchange resins

et al. 2010

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“…In Cohn’s method, five fractions could be obtained which are from fraction I to fraction V. The main component in each fraction has been shown in Table 2. Fraction I to V were prepared by adjusting parameters such as the concentration of ethanol, concentration of protein, temperature, and pH; concentration of ethanol from 8% reaches to 40% in preparation of fraction V. Nowadays, implementation of plasma fractionation is carried out by following chromatographic techniques (29). …”

Section: Human Plasma Fractionationmentioning

confidence: 99%

Implementation of Plasma Fractionation in Biological Medicines Production

Hosseini

Ghasemzadeh

2016

Iran. J. Biotechnol.

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Context The major motivation for the preparation of the plasma derived biological medicine was the treatment of casualties from the Second World War. Due to the high expenses for preparation of plasma derived products, achievement of self-sufficiency in human plasma biotechnological industry is an important goal for developing countries. Evidence Acquisition The complexity of the blood plasma was first revealed by the Nobel Prize laureate, Arne Tiselius and Theodor Svedberg, which resulted in the identification of thousands of plasma proteins. Among all these proteins, four of which are commercially important for production due to significant need of patients. These four products are: albumin, IgG, factor VIII, and Factor IX. The starting material for the production of biological drugs from plasma is natural which is different from synthetic starting material. So, the quality of plasma as starting material plays an important role in the quality of final product. Introducing new techniques for preparation of the biological drugs from human plasma has resulted in the improvements in purity of products, higher safety, and yield noticeably. Still, the backbone of the modern plasma fractionation technique is mainly based on cold ethanol fractionation of the human plasma that is almost the same as fractionation of crude oil, breaking it down into its components. The demand for IgG for treating immune deficiencies and coagulation factor VIII for hemophilia A determines how to design the plasma fractionation industry in terms of capacity. Nowadays, cold ethanol fractionation has followed by chromatographic methods, since they offer higher purity. In this review, we describe different methods of plasma fractionation such as cold ethanol fractionation, gel filtration, fractionation by salt, and fractionation by polyethylene glycol. There is no doubt that the four main products of human plasma are albumin, IgG, coagulation factor VIII, and IX, which their methods of separation from human plasma have been explained in this paper. Conclusions It can be concluded that plasma fractionation with ethanol at low temperature for the preparation of the main human plasma biological components including albumin, IgG, coagulation factors VIII, and IX is still the most widely used method at an industrial scale. Nowadays, this method is being used in combination with different chromatographic techniques in order to achieve a higher quality and the yield.

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“…They can be interesting alternatives to the current core process when/if demonstrated to perform efficiently at industrial scale and licensed by established regulatory authorities. A process based on expanded bed chromatography has been presented at pilot‐scale [27], where sequential chromatography of whole unfiltered plasma may result in significantly enhanced recovery of main protein fractions.…”

Section: Novel Plasma Fractionation Processesmentioning

confidence: 99%

Plasma fractionation

Burnouf

2012

ISBT Science Series

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The first plasma fractionation process was developed in the 1940s by Cohn and co‐workers to prepare albumin and immunoglobulins. It relies on sequential precipitation steps at negative temperatures, different ethanol concentrations and various pH to segregate bulk plasma proteins. The ‘Cohn procedure’ has been modified over the years but largely remains the core fractionation process in use up to now. The introduction of cryoprecipitation (thawing of plasma at 2–4°C), as the first plasma fractionation step, to isolate a crude factor‐VIII fraction, and the integration of chromatographic steps to extract labile plasma or trace plasma proteins, have eventually shaped the modern fractionation technologies into complex procedures. Viral inactivation and removal treatments are performed to prevent the risks of transmission of enveloped and non‐enveloped viruses. Viral inactivation steps are applied most often on pre‐purified fractions, the downstream steps being used to remove protein contaminants and viral inactivation agents. Depending upon products and protein stability, treatments include incubations with combinations of solvent (TnBP) and detergent (e.g. Tween 80 or Triton X‐100) (S/D), pasteurization (heat‐treatment in the liquid state at 60°C for 10 h in the presence of stabilizers), as well as low pH or caprylic acid treatments (these last two treatments are restricted to immunoglobulins). Nanofiltration, to capture viruses on nm‐membranes, is typically performed on the final purified protein fractions prior to sterile filtration and aseptic filling. Terminal dry‐heat treatment at 80–100°C is used for some coagulation factor preparations. Modern plasma protein products have an unprecedented level of quality and safety when there is careful process control and monitoring together with sensitive test methods to detect potentially harmful contaminants, such as procoagulant impurities. Since the implementation of validated robust viral reduction treatments, plasma products have a high viral safety profile including against emerging agents (WNV, Dengue virus, Chikungunya virus). Experimental spiking studies suggest that several fractionation steps are capable of removing prions causing variant Creutzfeldt‐Jakob disease. Alternative fractionation processes based exclusively on chromatography have been developed at pilot scale and need further validations to demonstrate the quality, safety and consistency of resulting plasma products. A mini‐pool viral inactivation and fractionation process relying on single‐use equipment is also being developed to facilitate the access to safer plasma components, including plasma for transfusion, cryoprecipitate, prothrombin complex, immunoglobulins and fibrin sealant, in particular in developing countries.

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A novel core fractionation process of human plasma by expanded bed adsorption chromatography

Cited by 26 publications

References 43 publications

Purification of coagulation factor VIII using chromatographic methods. Direct chromatography of plasma in anion exchange resins

Purification of coagulation factor VIII using chromatographic methods. Direct chromatography of plasma in anion exchange resins

Implementation of Plasma Fractionation in Biological Medicines Production

Plasma fractionation

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