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WO2025040552A1 - Procédé de filtration stérile de solutions aqueuses contenant de l'albumine - Google Patents

Procédé de filtration stérile de solutions aqueuses contenant de l'albumine Download PDF

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Publication number
WO2025040552A1
WO2025040552A1 PCT/EP2024/072965 EP2024072965W WO2025040552A1 WO 2025040552 A1 WO2025040552 A1 WO 2025040552A1 EP 2024072965 W EP2024072965 W EP 2024072965W WO 2025040552 A1 WO2025040552 A1 WO 2025040552A1
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Prior art keywords
filter
filtrate
albumin
opalescence
aqueous solution
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Pending
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PCT/EP2024/072965
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English (en)
Inventor
Michael BIERI
Michele ANDLER HIMMELSPACH
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CSL Behring AG
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CSL Behring AG
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Publication of WO2025040552A1 publication Critical patent/WO2025040552A1/fr
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/38—Albumins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0011—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
    • A61L2/0017—Filtration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/147—Microfiltration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D65/00—Accessories or auxiliary operations, in general, for separation processes or apparatus using semi-permeable membranes
    • B01D65/02—Membrane cleaning or sterilisation ; Membrane regeneration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/10—Supported membranes; Membrane supports
    • B01D69/105—Support pretreatment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/76—Albumins
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2311/00—Details relating to membrane separation process operations and control
    • B01D2311/26—Further operations combined with membrane separation processes
    • B01D2311/2688—Biological processes

Definitions

  • the present invention relates to a method for sterile filtration of an albumin-containing aqueous solution, as well as to an al- bumin solution obtained by a method disclosed herein. Further disclosed herein is the use of conditioned filters to reduce the opalescence of filtered aqueous solutions containing albumin.
  • Albumins of various types are of great importance as biochemi- cals, e.g. as components of culture media, cell culture media and as stabilisers for diagnostic agents in biology, medicine and pharmacy.
  • an obligatory step is the final pasteurisation of the product at 60 °C for 10 hours.
  • This heating step was introduced to inactivate infectious agents and to eliminate or reduce the risk of transmission of viruses, such as the hepatitis B virus, that may occur despite the various purification steps, owing to possible contamination of the biological raw material.
  • the albumin must be protected in order to prevent gelling during pasteurisation, with the aid of suitable stabilisers.
  • sodium caprylate and sodium acetyltryptophanate are generally used as stabilisers, either alone or in combination.
  • Sodium mandelate may also be used on its own or in combination with sodium caprylate.
  • the stabilisers are added in large excess relative to the albumin and, owing to their own affinity for al- bumin, are able to effectively protect it against direct dena- turation by heat.
  • Opalescence refers to the characteristic optical effect caused by light scattering in a milky-cloudy material, which is characterised by a coloured shimmer.
  • opalescence is classified from 0 to IV with 0, 3, 6, 18 or 30 nephelometric turbidity units (NTU) (European Pharmacopoeia 2016, EP9, section 2.2.1: "Clarity and degree of opalescence in liquids”).
  • NTU nephelometric turbidity units
  • US 5,118,794 discloses a process for stabilising human albumin solutions for therapeutic purposes for the purpose of their heat treatment in a container, wherein the method comprises the addi- tion of a surfactant in addition to the usual stabilising for- mula.
  • a surfactant in addition to the usual stabilising for- mula.
  • challenges associated with surfactants have been encountered, for instance, impurities, degradation and possible triggering of adverse immune reactions.
  • WO 2008/045563 relates to methods for reducing the opalescence of protein solutions and to compositions of con- centrated protein solutions with reduced opalescence.
  • the meth- ods include altering the ionic strength of the solutions such that the opalescent appearance and/or the amount of higher mo- lecular weight particles in the protein solution is reduced and/or eliminated, for example by decreasing the concentration of a salt present in the solution.
  • this document does not contain information on the reduction of opalescence in albumin-containing solutions.
  • the object of the present invention is to remedy these and other disadvantages of the prior art and, in particular, to provide a method for sterile filtration of an albumin-containing aqueous solution, in particular an aqueous solution containing the albu- min component of human blood.
  • a further object of the present invention is to provide safe and stable albumin solutions, in particular containing the albumin component of human blood, in which the opalescence associated with particle formation is eliminated or at least reduced.
  • the present invention features a method of sterile filtration of an albumin-containing aqueous solution, in particular an aqueous solution containing the albu- min portion of human blood.
  • the method comprises filtering the solution with at least one filter to obtain a filtrate.
  • the method is characterised in that it further comprises a step of conditioning the filter prior to filling the filtrate into at least one container by purging the at least one filter with a quantity of the albumin-containing aqueous solution, at a dif- ferential pressure across the respective filter of at most 1 bar and/or by pressure filtration, wherein the filtrate is main- tained at a back pressure of at least 0.5 bar (0.05 MPa) at the outlet of the respective filter.
  • sterile filtration is a process used to remove microorganisms such as bacteria and vi- ruses from liquids or gases, ensuring that the filtered medium is essentially free from microorganism contaminants, for example at a level which meets the requirements for sterility using standard testing methods as specified in the current edition of a default standard, such as the European Pharmacopeia or the United States Pharmacopeia, and which is suitable for sterile applications .
  • purging means wetting the filter, for example by rinsing.
  • the filtered albu- min solutions thus obtained are clear and have an opalescence which is reduced by at least one class compared to a filtrate obtained without the conditioned filter described herein.
  • the filtered albumin solutions thus obtained are clear and have an opalescence of at most class I, classified with 3 nephelometric turbidity units (NTU).
  • albumin-con- taining aqueous solution refers to any composition comprising water and at least albumin as the major protein component. More particularly, the term “albumin-containing aqueous solution” re- fers to any aqueous composition in which albumin comprises more than 80% of all proteins in the composition and which is in- tended for clinical treatment. Albumin-containing aqueous solu- tions as used in the context of the present invention are de- fined in particular in the European Pharmacopoeia under the ti- tle "human albumin solution”.
  • the human albumin which is the subject of the present invention is obtained in particular by extraction and purification by any suitable method from a human albumin source or also by culturing animal or plant cell cultures, bacteria or yeasts which have been transformed to produce human albumin by genetic engineering methods as known to the skilled person.
  • the filling process is started only after the conditioning of the at least one filter described herein, so that the filtrate in all containers has the advanta- geous properties with respect to long-term stability and, in particular, reduced opalescence.
  • NTU stands for "Nephelometric Turbidity Unit” and is the unit used to measure the turbidity of a liquid or the presence of suspended solids in a liquid. The higher the concentration of suspended solids in the liquid, the higher the turbidity. Stabi- lised formazine turbidity standards for opalescence are availa- ble, for example, under the trade name StablCal® from Hach Lange GmbH (Switzerland). The relationship between NTU and suspended solids is as follows: 1 mg/1 (ppm) corresponds to 3 NTU. The turbidity is measured by 90° light scattering.
  • the formation of the white de- posit which can be observed after some time at the liquid-air interface, can also be avoided by the method disclosed herein, which means that the packaging - and thus also the production - of filtered albumin solutions can be carried out more effi- ciently by the method disclosed herein, as fewer vials have to be sorted out in quality control.
  • the at least one filter is conditioned by purg- ing the at least one filter with a quantity of the albumin-con- taining aqueous solution by means of pressure filtration and maintaining the filtrate in the outlet of the respective filter at a back pressure of about 1 bar.
  • a rel- atively rapid and complete saturation of the filter with albumin can be achieved without subjecting the filter and/or the fil- trate to excessive stress which could damage the filter or ren- der the filtered albumin solution, i.e. the product (filtrate), unusable.
  • the at least one filter is conditioned by purging the at least one filter with a quantity of the albumin- containing aqueous solution by pressure filtration with an inlet pressure at the inlet of the respective filter of about 2 bar and maintaining the filtrate at the outlet of the respective filter with a back pressure of about 1 bar.
  • the quantity of the albumin-containing aqueous solution used for purging the at least one filter is between about 2.5 litres and about 11 litres per square metre of filter area of the at least one filter. In certain embodiments, the quantity of albumin-containing aqueous solution used to purge the at least one filter is about 10 litres for a filter area of the at least one filter of 1 square metre. Such a volume ensures good purging and saturation of the respective filter with albu- min.
  • the filtrate is recirculated after passing through the at least one filter. In this way, the consumption of albumin-containing aqueous solution can be reduced and the effi- ciency of the method can be further increased.
  • the at least one filter is conditioned by flushing the at least one filter with an quantity of the al- bumin-containing aqueous solution at a differential pressure across the respective filter of at most 1 bar, no back pressure is applied at the outlet of the respective filter.
  • the albumin solution of the filtrate has a particularly low opalescence, e.g. an opalescence class I classified as 3 NTU, if any.
  • the purging of the at least one filter with the quantity of the albumin-con- taining aqueous solution is carried out at a flow rate through the respective filter of about 2 to about 4 litres per minute per square metre of filter area of the at least one filter.
  • the at least one filter is purged with the quantity of albumin-containing aqueous solution at a flow rate through the respective filter of approximately 3 litres per minute per square metre of filter surface area of the at least one filter.
  • the at least one filter is rinsed with ultrapure water (water for infusion) before the respective filter is purged with the quantity of albumin-containing aqueous solution.
  • the volume of ultrapure water used to rinse the at least one filter is about 1 litre to about 11 litres per square metre of filter area of the at least one filter.
  • the volume of ultrapure water used to rinse the at least one filter is about 1 to 10 litres per square metre of filter area of the at least one filter.
  • the method further comprises a step of pasteur- ising the filtrate.
  • the pasteurisation of the filtrate is carried out at 60 °C for 10 h after filtration. Un- der these conditions, germs and viruses that have entered or are present in the filtered albumin solution despite upstream safety precautions are reliably inactivated and rendered harmless.
  • the filtrate is pasteurised in the at least one con- tainer. This eliminates the risk of recontamination of the fil- tered albumin solution by transferring it again.
  • the filtrate is successively filled into sterile vials, which are then sealed with a stopper.
  • the method further comprises a step of pasteur- ising the filtrate as described herein and a step of incubating the pasteurised filtrate to obtain an incubated filtrate.
  • the step of incubating the pasteurised filtrate is carried out over a period of about 10 to 20 days, preferably for about 15 to 20 days.
  • the step of incubating the pas- teurised filtrate is carried out for 15 or 16 days.
  • the incu- bated filtrate can be stored. The storage may, for example, be for a predetermined period of time.
  • the step of incubating the pasteurised fil- trate is carried out at a temperature between about 25 and about
  • the at least one filter is conditioned by purging the at least one filter with a quantity of the albu- min-containing aqueous solution by means of pressure filtration and the filtrate in the outlet of the respective filter is main- tained at a back pressure of at least 0.5 bar, the back pressure is monitored at least during the conditioning of the respective filter.
  • the at least one filter is conditioned by purging the at least one filter with a quantity of the albu- min-containing aqueous solution by means of pressure filtration and the filtrate in the outlet of the respective filter is main- tained at a back pressure of at least 0.5 bar
  • the purging of the respective filter with the quantity of the albumin-contain- ing aqueous solution is carried out at a flow rate through the respective filter of about 1 litre to about 3 litres per minute per square metre of filter area of the at least one filter.
  • the respective filter is purged with the quantity of albumin-containing aqueous solution at a flow rate through the respective filter of approximately 2 litres per minute per square metre of filter surface area of the at least one filter.
  • the albumin is selected from human serum albu- min, bovine serum albumin, egg albumin and recombinant human se- rum albumin.
  • the albumin concentration in the albumin-con- taining aqueous solution and/or filtrate is between 19 % and 30 %, based on the total weight of the albumin-containing aqueous solution and/or filtrate, respectively. This is done prior to and/or after filtration.
  • the albumin concentra- tion in the albumin-containing aqueous solution and/or in the filtrate before and/or after filtration is between 3 % and 6 %, based on the total weight of the albumin-containing aqueous so- lution and/or filtrate, respectively. Again, this is done prior to and/or after filtration.
  • the method further comprises a step of pasteur- ising the filtrate to obtain a pasteurised filtrate and a step of evaluating the opalescence of the pasteurised filtrate.
  • the opalescence of the filtrate is evaluated by measur- ing turbidity or evaluating a change in the formation of higher molecular weight particles.
  • higher molecular weight particles refers to an asso- ciation of at least two molecules.
  • the molecules are lipids and/or proteins, e.g. albumins, wherein the protein association results in the formation of higher order ag- gregates of monomeric protein.
  • the association can result from non-covalent (e.g. electrostatic, van der Waals) protein-protein interactions.
  • the proteins can be identical or different.
  • the higher molecular weight particles typically have a molecular weight of about 10 4 Da or higher, typically about 10 6 Da or higher.
  • the weight average molecular weight of the aggregated molecules in the solution can be detected, for example, by one or more of the following methods: Light scattering techniques such as static and/or dynamic light scattering, or asymmetric flow field flux fractionation. Details of the above measurement methods are described in more detail below.
  • Light scattering techniques such as static and/or dynamic light scattering, or asymmetric flow field flux fractionation. Details of the above measurement methods are described in more detail below.
  • the opalescence of the samples after pas- teurisation and incubation can be determined.
  • the method further comprises a step of pasteurising the filtrate, in particular as described herein, to obtain a pasteurised filtrate, a step of incubating the pasteurised fil- trate to obtain an incubated filtrate, and a step of evaluating the opalescence of the incubated filtrate.
  • the opalescence may be evaluated immediately af- ter pasteurisation and/or incubation.
  • the step of eval- uating the opalescence of the pasteurised and optionally incu- bated filtrate can also be carried out after the corresponding filtrate has been stored for about one day to several years, in particular for about five years.
  • the step of evalu- ating the opalescence of the pasteurised and optionally incu- bated filtrate is carried out after the corresponding filtrate has been stored for about 1 to 6 months, preferably after the corresponding filtrate has been stored for about 1 to 3 months.
  • the opalescence of the incubated filtrate can be assessed at the temperature at which the incubation is carried out, in particu- lar at a temperature of about 29 °C to about 31 °C. Alterna- tively or additionally, the opalescence can also be evaluated at the temperature at which the incubated filtrate is stored. This temperature may depend on the product in question and may, for example, be between about 2°C and about 8°C or ambient tempera- ture. It is also conceivable that the opalescence of the incu- bated filtrate is evaluated neither at the incubation tempera- ture nor at the storage temperature, but at room temperature in a laboratory. The term "room temperature” is understood by the skilled person and can in particular mean a temperature of about 20 °C.
  • the opalescence of the incubated filtrate is evaluated at a temperature of 3 ⁇ 5 °C.
  • the opalescence of the incubated filtrate is evaluated at a temperature of 3 ⁇ 0 °C, more preferably at a temperature of 2 ⁇ 5 °C.
  • the opalescence of the incubated filtrate is evaluated at a temperature of approximately 20 °C.
  • the opalescence of the incubated filtrate is evaluated at a temperature between about 2 °C and about 8 °C.
  • the opalescence of the filtrate and/or the incu- bated filtrate is assessed by one or more of the following meth- ods: visual inspection, dynamic light scattering and tunable re- sistive pulse sensing (TRPS).
  • meth- ods visual inspection, dynamic light scattering and tunable re- sistive pulse sensing (TRPS).
  • the filtrate and/or the incubated filtrate has/have an opalescence that is reduced by at least one class when compared to a filtrate of the same albumin-containing aqueous solution that has not been filtered through the conditioned filter.
  • the pasteurised filtrate and/or the incubated filtrate has/have at most a class I opalescence, classified as 3 NTU.
  • the filtrate and/or the incubated fil- trate when assessed 2 months after filtration, exhibits at most Class I opalescence, classified as 3 NTU.
  • the albumin-containing aqueous solution is ap- plied to the at least one filter at a pressure of approximately 1 bar. At this pressure, a good throughput can be achieved with- out overloading the filter or the albumin-containing aqueous so- lution.
  • the at least one filter has a filter area of about 0.01 to about 0.8 m 2 .
  • the at least one filter has a filter area of about 0.4 m 2 . With this filter surface area, a relatively large volume, as occurs in the production of fil- tered albumin solutions in the pharmaceutical industry, can be filtered in an acceptable time.
  • the pore size of the at least one filter is approxi- mately 0.22 pm or less.
  • the at least one filter is a double- layer filter equipped with two membranes
  • the pore size of the membrane arranged first in the flow direction of the filter can have a larger pore size than the membrane arranged downstream in the flow direction, i.e. the membrane of the sterile filter.
  • the first of the two membranes arranged in the flow direction of the double-layer filter may have a pore size of about 0.45 pm or smaller, and the pore size of the other mem- brane arranged downstream in the flow direction of the double- layer filter, i.e. the membrane of the sterile filter, may be about 0.22 pm or smaller.
  • the pore size of the filter can be 0.22 pm or 0.20 pm.
  • Mem- branes with such a pore size enable the desired sterilisation effect without excessively restricting the flow through the fil- ter.
  • the at least one filter is a polyethersulfone (PES) membrane filter or a nylon filter.
  • PES polyethersulfone
  • Such filters are suita- ble for use in the pharmaceutical industry and are generally readily available.
  • the method prior to filtering the albumin-containing aque- ous solution with the at least one filter, the method further comprises a step of filtering the albumin-containing aqueous so- lution with a pre-filter, wherein the pore size of the pre-fil- ter is about 0.45 pm or smaller.
  • the amount of stabiliser added to the albumin-containing aqueous solution is proportional to the albumin concentration of the so- lution in question.
  • the albumin-containing aque- ous solution is stabilised with about 0.08 mM of at least one stabiliser selected from sodium N-acetyltryptophanate and sodium caprylate per gram of albumin. This amount can effectively pro- tect the albumin molecules from heat denaturation during pas- teurisation and reduce the formation of aggregates to achieve stability over a desired period of time, in particular over the shelf life of the final albumin product, e.g. for at least 1 month, preferably for at least 3 months, more preferably for at least 6 months, most preferably for one year or longer.
  • the present invention relates to a filtered albumin solution obtained by the method of sterile filtration disclosed herein, in particular a pharmaceutical composition comprising the filtered albumin solution.
  • a filtered albumin solution obtained by the method of sterile filtration disclosed herein, in particular a pharmaceutical composition comprising the filtered albumin solution.
  • Such an albumin solu- tion is characterised by lower opalescence compared to a compa- rable albumin solution which has been filtered through one or more filters, but which has not been conditioned as described herein.
  • the present invention relates to the use of a filter which has been conditioned by purging with an quantity of an albumin-containing aqueous solution either at a differen- tial pressure across the filter of at most 1 bar or by pressure filtration and holding the filtrate in the outlet of the filter at a back pressure of at least 0.5 bar, for reducing the opales- cence of the filtered albumin-containing aqueous solution.
  • Figure 1 Schematic illustration of a visual inspection box used to test for opalescence
  • Figure 2 Schematic illustration of the sterile filtration set-up
  • Figure 3 Summary of the results of the visual inspection for examples 1-3;
  • Figure 4 Image showing the opalescence of the vials from examples 1-3;
  • Figure 5 Image showing white deposit rings of the vials from examples 1-3;
  • Figure 6 Summary of the optical density results for exam- pies 1-3;
  • Figure 7 Summary of the turbidity results for examples 1-3;
  • Figure 8 Schematic illustration of filtration with applied back pressure;
  • Figure 9 Schematic illustration of filtration with reduced pressure
  • a visual control box 20 with black inner walls 21 and a white light source 22 mounted in the upper part of the box was used to examine samples for opalescence and to determine the degree of opalescence.
  • the sample containers 10, 10' were placed in front of a slit 23 in the box so that the containers 10, 10' were ex- posed to indirect light, as shown schematically in Figure 1.
  • the opalescence was classified according to the European Pharmaco- poeia 11.2, 2023, "2.2.1 Clarity and degree of opalescence of liquids" in class 0 - IV (corresponding to 0, 3, 6, 18 and 30 NTU, respectively).
  • Dynamic light scattering was measured with a Malvern Zetasizer nano zs to determine the particle size distribution (non-quantitative) in the size range of 0.4 - 7000 nm, the mean Z-average (Z-Ave) and the optical density (mean derived count rate (DCR), in kcps).
  • Z-Ave is the harmonic mean of the in- tensity-weighted hydrodynamic diameter, which was previously used as a reference value for the evaluation of albumin opales- cence.
  • the mean derived count rate (DCR) gives an indication of the number of particles.
  • NTUs nephelometric turbidity units
  • the 20 % albumin diafiltrate prepared from the Kistler/Nitschmann precipitate C was concentrated and formulated with the stabilisers tryptophan and caprylic acid (20 mM each) to albumin 25 %.
  • This bulk albumin solution was aerated by blow- ing compressed air directly into the solution with a nozzle, causing small air bubbles to form. The flow rate was adjusted so that bubbles formed continuously.
  • a 0.22 pm filter was connected to the inlet of the con- tainer with the bulk albumin solution. Aeration was carried out over a period of 6 hours.
  • the starting material obtained in this way was used as an albumin-containing aqueous solution in the comparative experiments.
  • the reference samples were prepared by filtering the starting material as described above without conditioning the filter.
  • a schematic representation of the sterile filtration set-up is shown in Figure 2.
  • the albumin-containing aqueous solution 2 was filtered using a pump (not shown), which provided a pressure of
  • the filter 3 used was a disposable cartridge with a pore size of 0.2 pm and a sterile filter area of 0.015 m 2 , which contained the same material and the same pleated filter membrane as the 10-inch filters normally used on a production scale.
  • the filter 3 was first rinsed with 260 mL ultrapure water (not shown) and then purged with 150 mL albumin-containing aqueous solution 2.
  • the filtrate 1 of the albumin solution was successive- sively collected in 2050 mL vials 10, which were immediately sealed with a stopper (not shown).
  • the vials 10 were then pas- teurised at 60 °C for 10 hours and incubated at 30 °C for 15 days.
  • the resulting 20 samples served as a reference to which the samples obtained by the improved method according to the present invention were compared.
  • the vials containing the reference samples were visu- ally assessed for white rings on the inside of the vials at the liquid-air interface two months after their incubation, and in- deed white rings were observed in the reference sample vials, as indicated by the white arrow in Figure 5 (centre image; Ex. 1).

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Abstract

La présente invention concerne un procédé de filtration stérile d'une solution aqueuse contenant de l'albumine (2), le procédé comprenant le filtrage de la solution (2) avec au moins un filtre (3) pour obtenir un filtrat (1), le ou les filtres (3) étant conditionnés avant le remplissage du filtrat (1) dans au moins un récipient (10, 10') par purge du ou des filtres (3) avec une quantité (5) de la solution aqueuse contenant de l'albumine (2) i) à une pression différentielle à travers le filtre respectif (3) ne dépassant pas 1 bar et/ou ii) au moyen d'une filtration sous pression, le filtrat (1) étant maintenu dans la sortie (4) du filtre respectif (3) à une contre-pression d'au moins 0,5 bar.
PCT/EP2024/072965 2023-08-18 2024-08-15 Procédé de filtration stérile de solutions aqueuses contenant de l'albumine Pending WO2025040552A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CHCH000876/2023 2023-08-18
CH000876/2023A CH720224B1 (de) 2023-08-18 2023-08-18 Verfahren zur Sterilfiltration albuminhaltiger wässriger Lösungen

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WO2025040552A1 true WO2025040552A1 (fr) 2025-02-27

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Citations (6)

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US5118794A (en) 1988-04-14 1992-06-02 Institut Merieux Process for stabilizing human albumin solutions and the solution obtained
ES2294976A1 (es) * 2007-11-12 2008-04-01 Grifols, S.A. "procedimiento de obtencion de albumina human de alta eficacia para su uso en terapia de toxificacion".
WO2008045563A2 (fr) 2006-10-12 2008-04-17 Wyeth Procédés et compositions ayant une opalescence réduite
WO2009073569A2 (fr) * 2007-11-30 2009-06-11 Abbott Laboratories Formulations de protéine et leurs procédés de fabrication
WO2014015388A1 (fr) * 2012-07-27 2014-01-30 Csl Limited Procédé de polissage d'albumine
US20230007847A1 (en) * 2007-11-30 2023-01-12 Abbvie Biotechnology Ltd Protein formulations and methods of making same

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5118794A (en) 1988-04-14 1992-06-02 Institut Merieux Process for stabilizing human albumin solutions and the solution obtained
WO2008045563A2 (fr) 2006-10-12 2008-04-17 Wyeth Procédés et compositions ayant une opalescence réduite
ES2294976A1 (es) * 2007-11-12 2008-04-01 Grifols, S.A. "procedimiento de obtencion de albumina human de alta eficacia para su uso en terapia de toxificacion".
WO2009073569A2 (fr) * 2007-11-30 2009-06-11 Abbott Laboratories Formulations de protéine et leurs procédés de fabrication
US20230007847A1 (en) * 2007-11-30 2023-01-12 Abbvie Biotechnology Ltd Protein formulations and methods of making same
WO2014015388A1 (fr) * 2012-07-27 2014-01-30 Csl Limited Procédé de polissage d'albumine

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"European Pharmacopoeia", vol. 11, 2023, article "2.2.1 Clarity and degree of opalescence of liquids"
ZALOGA JAN ET AL: "Pharmaceutical formulation of HSA hybrid coated iron oxide nanoparticles for magnetic drug targeting", EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, ELSEVIER SCIENCE PUBLISHERS B.V., AMSTERDAM, NL, vol. 101, 8 February 2016 (2016-02-08), pages 152 - 162, XP029459762, ISSN: 0939-6411, DOI: 10.1016/J.EJPB.2016.01.017 *

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