Methods for evaluating suitability of a biochemical filter
AssigneeRegeneron Pharmaceuticals, Inc.
InventorsNathan Mao, Annamarie Cruz, Bernhard Schilling, Scott Carver
Life of this patent
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Abstract
Embodiments of the present disclosure include methods and systems for detecting the presence of endotoxins in filters. For example, embodiments of the present disclosure are directed to methods and systems for improving in-process controls by detecting undesirable quantities of endotoxins in filters containing naturally-sourced materials prior to using those filters in the production of formulated drug substances.
Claims21
A method for evaluating suitability of a plurality of filters for use in a biologic purification process, the method comprising:
- selecting a filter from the plurality of filters, wherein each of the plurality of filters comprises cellulose;
- passing a volume of a buffer solution through the selected filter, wherein the buffer solution has a conductivity of at least about 40 mS/cm at 25° C. when tested in accordance with ASTM D1125, and the buffer solution is configured to remove endotoxins from the selected filter;
- performing an assay of the buffer solution passed through the selected filter to detect a presence of an endotoxin removed from the selected filter;
- evaluating the suitability of the plurality of filters for use in the biologic purification process based on a result of the assay;
- and
- repeating the selecting, passing, performing, and evaluating steps at periodic time intervals.
A method for detecting presence of an endotoxin, the method comprising:
- contacting a naturally-sourced material with a buffer solution, wherein the naturally-sourced material comprises cellulose, and wherein the buffer solution is configured to remove the endotoxin from the naturally-sourced material;
- and
- performing an assay of the buffer solution passed through the naturally-sourced material to detect a presence of the endotoxin removed from the naturally-sourced material in the buffer solution,
- wherein the buffer solution comprises tris(hydroxymethyl)aminomethane, citrate, histidine, arginine, or mixtures thereof.
A method for determining suitability of a buffer solution for use in an endotoxin detection process, the method comprising:
- passing the buffer solution through a first filter of a filter lot, the filter lot including a plurality of filters comprising naturally-sourced materials, wherein the buffer solution comprises tris(hydroxymethyl)aminomethane, citrate, histidine, arginine, or mixtures thereof, and the buffer solution is configured to remove the endotoxin from the first filter via disrupting one of an electrostatic interaction or a hydrophobic interaction between the endotoxin and the first filter;
- assaying the buffer solution passed through the first filter to detect a quantity of the endotoxin removed from the first filter and present in the buffer solution;
- passing a cell culture fluid through a second filter of the filter lot;
- assaying the cell culture fluid passed through the second filter to detect a quantity of the endotoxin removed from the second filter and present in the cell culture fluid;
- and
- comparing the quantity of the endotoxin detected in the buffer solution to the quantity of the endotoxin detected in the cell culture fluid.
A method, the method comprising:
- passing at least 25 L/m2 of a buffer solution through a filter, wherein the buffer solution is configured to remove endotoxins from the filter, thereby washing endotoxins from the filter before use, and
- assaying the buffer solution passed through the filter, wherein the buffer solution has a conductivity of at least about 40 mS/cm at 25° C. when tested in accordance with ASTM D1125,
- wherein the filter is a harvest depth filter, the harvest depth filter comprises naturally-sourced materials and the naturally-sourced materials comprise cellulose.
Dependencies are inferred from the claim text.