University of Connecticut

Baxalta Gmbh

Baxter International Inc.

Other

Purdue Research Foundation

Michael Pikal

Marc Besman

Serguei Tchessalov

Erik Bjornson

Feroz Jameel

John Frank Carpenter

Ramesh Kashi

Xiaolin Tang

Steven L Nail

Serguei University Of Connecticut Tchessalov

A Factor VIII (FVIII) composition formulated such that NaCl is not present in the final formulation or is present in trace amounts, which allows for a concomitant reduction in the lyophilization cycle time and increased stability of the lyophilized FVIII.

Factor VIII formulations

A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent.

Albumin-free factor VIII formulations

An albumin-free Factor VIII formulation comprising: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent.

A method by which a freeze-drying process may be developed from a single freeze-drying experiment. The method uses in-process manometric temperature measurement (MTM) data to optimize the primary drying conditions. Manometric temperature measurement is a procedure by which the product temperature at the sublimation interface and the resistance of the previously dried product to vapor flow may be determined. The inventive method can be used in an inventive freeze-drying system. The system comprises a freeze-dryer, a measurement system including hardware and software necessary for generation of MTM data and a control system including hardware and software for interpretation of the generated MTM data and control of the freeze-dryer. The measurement system and control system may be combined into a single device. The inventive freeze-drying system utilizes a microprocessor and software to define conditions for the freezing and secondary drying stages and to define chamber pressure and 'target product temperature' for the primary drying stage based on MTM data and operator input data, thereby providing a near optimized freeze-drying process.

Automated process control using manometric temperature measurement

Albumin-free Factor VIII formulations

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Mansfield Center, CT, United States of America

Michael Pikal