Method for preserving biopharmaceuticals
Inventors
Assignees
Universal Stabilization Technologies Inc • Universal Stabilization Technologies Inc
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Publication Number
US-11400051-B2
Publication Date
2022-08-02
Expiration Date
Abstract
The disclosure concerns methods for executing PBV protocols to preserve biopharmaceuticals using a conventional lyophilizer. Also described are steps for maintaining isolation of a biopharmaceuticals for achieving aseptic drying using the conventional lyophilizer. As a collateral benefit, the invention provides good manufacturing practice (GMP) compliant methods for achieving aseptic drying of biopharmaceutical compositions using a conventional lyophilizer disposed outside of a clean-room area. Finally, methods and formulations str disclosed for preserving biopharmaceuticals suitable for mucosal or transdermal delivery to a patient.
Core Innovation
The invention relates to preserving biopharmaceuticals by executing preservation in a vacuum chamber of a lyophilizer using a multi-stage protocol. The method provides an aqueous preservation composition within a container that includes one or more biopharmaceuticals and places the container and preservation composition on a temperature-controlled shelf adapted to provide a shelf-temperature while the vacuum chamber is adapted to provide a vacuum-pressure therein.
The process executes a partial freezing protocol, then a primary drying protocol, and then a secondary drying protocol. In the partial freezing protocol, the shelf-temperature is decreased below 0° C and maintained so that the preservation composition temperature remains above Tg′, thereby transforming the preservation composition into a two-phase slush state comprising ice crystals and aqueous liquid-phase.
In the primary drying protocol, the shelf-temperature is increased above 0° C and the vacuum-pressure is maintained below 1.0 Torr, boiling water from the two-phase slush state to form a mechanically-stable glassy foam. In the secondary drying protocol, the shelf-temperature is increased above 40° C to increase the glass transition temperature of the mechanically-stable glassy foam.
In related embodiments, the preservation composition and containers can be constrained to support processing and isolation, including the use of a porous membrane and sterile medical-grade sterilization pouch for aseptic production and optional transformation of the mechanically-stable glassy foam into a powder.
Claims Coverage
The document includes two independent claims: one for a preservation method for biopharmaceuticals using a multi-stage PBV lyophilization protocol with controlled shelf temperature and vacuum pressure, and another for aseptic production of thermostable biopharmaceuticals that combines container membrane sealing, sterile pouch heat-sealing in a clean room, vacuum-shelf drying into a mechanically-stable glassy foam, and post-drying humidity isolation in the clean room. Across the independent claims, the coverage centers on transforming an aqueous preservation composition through a two-phase slush state and into a mechanically-stable glassy foam with controlled glass transition temperature development, including specific container isolation measures for aseptic production.
Multi-stage preservation into a two-phase slush and mechanically-stable glassy foam
A method for preserving biopharmaceuticals comprising providing an aqueous preservation composition within a container, placing the container and preservation composition on a temperature-controlled shelf within a vacuum chamber of a lyophilizer, executing a partial freezing protocol to transform the preservation composition into a two-phase slush state comprising ice crystals and aqueous liquid-phase, executing a primary drying protocol to form a mechanically-stable glassy foam by boiling water under vacuum, and executing a secondary drying protocol to increase the glass transition temperature of the mechanically-stable glassy foam.
Aseptic production using membrane-sealed container sterilization and vacuum-shelf drying
A method for aseptic production of thermostable biopharmaceuticals comprising placing a preservation composition inside a container within a first area of a clean room, sealing an opening with a porous membrane to form a membrane-sealed container, placing the membrane-sealed container within a sterile medical-grade sterilization pouch and heat-sealing the sterilization pouch, exporting the sterilization pouch and membrane-sealed container to a second area for lyophilizer drying while transforming the preservation composition into a mechanically-stable glassy foam, and subsequent to executing the drying protocol removing the membrane-sealed container from the sterilization pouch prior to returning to the first area of the clean room and replacing the porous membrane with a sterile cup or covering the filter with a water-impermeable sterile sticker to ensure the mechanically-stable glassy foam remains isolated from external humidity during subsequent storage.
Claim coverage is anchored in (1) executing partial freezing to form a two-phase slush state followed by primary and secondary drying to form a mechanically-stable glassy foam with increased glass transition temperature, and (2) incorporating aseptic clean-room workflow with a membrane-sealed container, sterilization in a heat-sealed medical-grade pouch, lyophilizer vacuum drying into the mechanically-stable glassy foam, and post-drying humidity isolation using a sterile cup or a water-impermeable sterile sticker.
Stated Advantages
Enables formation of a mechanically-stable glassy foam during primary drying.
Increases the glass transition temperature of the mechanically-stable glassy foam during secondary drying.
Provides aseptic production of thermostable biopharmaceuticals using membrane-sealed container sterilization and clean-room replacement of the porous membrane to maintain isolation from external humidity during subsequent storage.
Documented Applications
Aseptic production of thermostable biopharmaceuticals in a clean room with drying in a lyophilizer into a mechanically-stable glassy foam, with subsequent humidity isolation for storage; optionally transforming the mechanically-stable glassy foam into a powder.
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