Lyophilization of High-Concentration Protein Formulations

2018 ◽  
pp. 291-325 ◽  
Author(s):  
Patrick Garidel ◽  
Ingo Presser
Keyword(s):  
High Concentration ◽  
Protein Formulations

Prediction of colloidal stability of high concentration protein formulations

2014 ◽  
Vol 20 (3) ◽  
pp. 367-374 ◽  
Author(s):  
Patrick Garidel ◽  
Alfred Blume ◽  
Michael Wagner
Keyword(s):  
Colloidal Stability ◽  
High Concentration ◽  
Protein Formulations

A Direct Method to Monitor Glutathione Stability in High Concentration Protein Formulations

2021 ◽  
Vol 20 ◽  
Author(s):  
Seth Keever ◽  
Bassam Nakhle ◽  
Bernice Yeung
Keyword(s):  
Protein Stability ◽  
Direct Method ◽  
Antioxidant Properties ◽  
Direct Analysis ◽  
Reversed Phase ◽  
High Concentration ◽  
Analytical Methodology ◽  
Pharmaceutical Protein ◽  
Protein Formulations ◽  
Charged Aerosol

Due to its antioxidant properties and favorable safety profile, glutathione (GSH) finds use in protein formulations by improving overall protein stability. Once degraded, primarily by oxidation into glutathione disulfide (GSSG), the protecting effect of GSH is lost. A simple, direct method using reversed-phase separation and charged-aerosol detection (RP-CAD) to quantitate GSH is described in this paper. The analytical methodology is also capable of monitoring several by-product degradants of GSH, both oxidative and non-oxidative. For high-concentration protein formulations, the method provides direct analysis of GSH and its degradants in the presence of protein at up to 225 mg/mL simply through a dilution of the sample. Quantitation of many amino acids typically included in pharmaceutical protein formulations is also possible. Use of an online diverting valve in the method prevents interference in the detector from the high protein concentration in formulation. Accuracy and effectiveness of this method is demonstrated through monitoring the stability of GSH in high-concentration protein formulations through confirmation of GSH concentration and mass-balance of its loss over time. Monitoring GSH stability in protein formulations is necessary, as GSH concentration is indicative of protein stability.

Use of ferric thiocyanate derivatization for quantification of polysorbate 80 in high concentration protein formulations

Talanta ◽  
2014 ◽  
Vol 130 ◽  
pp. 542-546 ◽  
Author(s):  
Nimesh Savjani ◽  
Eugene Babcock ◽  
Hui Koon Khor ◽  
Anil Raghani
Keyword(s):  
Polysorbate 80 ◽  
High Concentration ◽  
Ferric Thiocyanate ◽  
Protein Formulations

Rational design of lyophilized high concentration protein formulations-mitigating the challenge of slow reconstitution with multidisciplinary strategies

2013 ◽  
Vol 85 (2) ◽  
pp. 287-293 ◽  
Author(s):  
Wenjin Cao ◽  
Sampathkumar Krishnan ◽  
Margaret Speed Ricci ◽  
Liang-Yu Shih ◽  
Dingjiang Liu ◽  
...  
Keyword(s):  
Rational Design ◽  
High Concentration ◽  
Protein Formulations

High-concentration protein formulations: How high is high?

2017 ◽  
Vol 119 ◽  
pp. 353-360 ◽  
Author(s):  
Patrick Garidel ◽  
Alexander B. Kuhn ◽  
Lars V. Schäfer ◽  
Anne R. Karow-Zwick ◽  
Michaela Blech
Keyword(s):  
High Concentration ◽  
Protein Formulations

scholarly journals US FDA approved therapeutic antibodies with high concentration formulation: Summaries and perspectives

2021 ◽  
Author(s):  
Shawn Shouye Wang ◽  
Yifei Susie Yan ◽  
Kin Ho
Keyword(s):  
Protein Concentration ◽  
Future Trend ◽  
Therapeutic Antibody ◽  
Formulation Development ◽  
High Concentration ◽  
Protein Formulations ◽  
Fda Approval ◽  
High Protein Concentration ◽  
The Us ◽  
Us Fda

Abstract Since 1986 when we first witnessed the approval of monoclonal antibody (mAb) Orthoclone OKT3 by the US FDA, FDA has approved 103 therapeutic antibody drugs in the past 35 years for marketing. Thirty four (34) of these 103 therapeutic antibody drugs (accounting for one third of the total FDA approved antibody therapeutics) are formulated with high protein concentration (100 mg/mL or above). These 34 high concentration antibodies are the focus of this article. The dosage forms of these 34 antibodies are analyzed and discussed in this article. The highest protein concentration of these approved mAbs is 200 mg/mL. The dominant administration route is subcutaneous (76%). Our analysis indicates that it may be rational to implement a platform formulation containing polysorbate, histidine and sucrose to accelerate high concentration formulation development for antibody drugs. The top players/sponsors of high concentration formulation are identified as Roche including its subsidiaries Genentech and Chugai, Novartis, Sanofi, Amgen, GSK, Johnson & Johnson including its subsidiary Janssen, and Regeneron. The FDA approval numbers are significantly increased since 2015 which account for 76% of the total approval number, i.e., 26 out of 34 highly concentrated antibodies. Thus, we believe that the high concentration formulations of antibody drugs will be the future trend of therapeutic antibody formulation development, regardless of the challenges of highly concentrated protein formulations.

Key Factors Governing the Reconstitution Time of High Concentration Lyophilized Protein Formulations

2021 ◽  
Author(s):  
Shreya S. Kulkarni ◽  
Sajal M. Patel ◽  
Raj Suryanarayanan ◽  
Joseph V. Rinella ◽  
Robin H. Bogner
Keyword(s):  
Key Factors ◽  
High Concentration ◽  
Protein Formulations

FTIR and nDSC as Analytical Tools for High-Concentration Protein Formulations

2006 ◽  
Vol 23 (6) ◽  
pp. 1350-1363 ◽  
Author(s):  
Susanne Matheus ◽  
Wolfgang Friess ◽  
Hanns-Christian Mahler
Keyword(s):  
High Concentration ◽  
Protein Formulations ◽  
Analytical Tools

Mechanisms by which crystalline mannitol improves the reconstitution time of high concentration lyophilized protein formulations

2018 ◽  
Vol 131 ◽  
pp. 70-81 ◽  
Author(s):  
Shreya S. Kulkarni ◽  
Raj Suryanarayanan ◽  
Joseph V. Rinella ◽  
Robin H. Bogner
Keyword(s):  
High Concentration ◽  
Protein Formulations
Sign in / Sign up

Export Citation Format

Share Document