A Formulation Development Approach to Identify and Select Stable Ultra–High-Concentration Monoclonal Antibody Formulations With Reduced Viscosities

2017 ◽  
Vol 106 (11) ◽  
pp. 3230-3241 ◽  
Author(s):  
Neal Whitaker ◽  
Jian Xiong ◽  
Samantha E. Pace ◽  
Vineet Kumar ◽  
C. Russell Middaugh ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Formulation Development ◽  
High Concentration ◽  
Development Approach

scholarly journals Improved Fluorescence Methods for High-Throughput Protein Formulation Screening

2018 ◽  
Vol 23 (6) ◽  
pp. 516-528 ◽  
Author(s):  
Yangjie Wei ◽  
Nicholas R. Larson ◽  
Siva K. Angalakurthi ◽  
C. Russell Middaugh
Keyword(s):  
Steady State ◽  
High Throughput ◽  
Protein Formulation ◽  
Formulation Development ◽  
High Concentration ◽  
Direct Optimization ◽  
Biophysical Characterization ◽  
Formulation Optimization ◽  
Long Term Storage ◽  
High Protein Concentration

The goal of protein formulation development is to identify optimal conditions for long-term storage. Certain commercial conditions (e.g., high protein concentration or turbid adjuvanted samples) impart additional challenges to biophysical characterization. Formulation screening studies for such conditions are usually performed using a simplified format in which the target protein is studied at a low concentration in a clear solution. The failure of study conditions to model the actual formulation environment may cause a loss of ability to identify the optimal condition for target proteins in their final commercial formulations. In this study, we utilized a steady-state/lifetime fluorescence-based, high-throughput platform to develop a general workflow for direct formulation optimization under analytically challenging but commercially relevant conditions. A high-concentration monoclonal antibody (mAb) and an Alhydrogel-adjuvanted antigen were investigated. A large discrepancy in screening results was observed for both proteins under these two different conditions (simplified and commercially relevant). This study demonstrates the feasibility of using a steady-state/lifetime fluorescence plate reader for direct optimization of challenging formulation conditions and highlights the importance of performing formulation optimization under commercially relevant conditions.

scholarly journals High concentration tangential flow ultrafiltration of stable monoclonal antibody solutions with low viscosities

2016 ◽  
Vol 508 ◽  
pp. 113-126 ◽  
Author(s):  
Jessica J. Hung ◽  
Ameya U. Borwankar ◽  
Barton J. Dear ◽  
Thomas M. Truskett ◽  
Keith P. Johnston
Keyword(s):  
Monoclonal Antibody ◽  
High Concentration ◽  
Tangential Flow

Lyophilization Cycle Development for a High-Concentration Monoclonal Antibody Formulation Lacking a Crystalline Bulking Agent

2007 ◽  
Vol 96 (6) ◽  
pp. 1598-1608 ◽  
Author(s):  
James D. Colandene ◽  
Linda M. Maldonado ◽  
Alma T. Creagh ◽  
John S. Vrettos ◽  
Kenneth G. Goad ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bulking Agent ◽  
High Concentration

scholarly journals The measurement and control of high-risk host cell proteins for polysorbate degradation in biologics formulation

2022 ◽  
Author(s):  
Xuanwen Li ◽  
Fengqiang Wang ◽  
Hong Li ◽  
Douglas D Richardson ◽  
David J Roush
Keyword(s):  
High Risk ◽  
Host Cell ◽  
Method Development ◽  
Control Strategies ◽  
Ionic Surfactant ◽  
Formulation Development ◽  
High Concentration ◽  
Host Cell Proteins ◽  
And Control ◽  
Measurement And Control

Abstract Non-ionic surfactant polysorbates (PS), including PS-80 and PS-20, are commonly used in the formulation of biotherapeutic products for both preventing surface adsorption and acting as stabilizer against protein aggregation. Trace levels of residual host cell proteins (HCPs) with lipase or esterase enzymatic activity have been shown to degrade polysorbates in biologics formulation. The measurement and control of these low-abundance, high-risk HCPs for polysorbate degradation is an industry-wide challenge to achieve desired shelf-life of biopharmaceuticals in liquid formulation, especially for high-concentration formulation product development. Here, we reviewed the challenges, recent advances and future opportunities of analytical method development, risk assessment and control strategies for polysorbate degradation during formulation development with a focus on enzymatic degradation. Continued efforts to advance our understanding of polysorbate degradation in biologics formulation will help develop high-quality medicines for patients.

‘Mutual Prodrug’ and approach to increase the effectiveness of Non-Steroidal Anti-inflammatory Drugs

2021 ◽  
Vol 1 (1) ◽  
pp. 035-045
Author(s):  
Manish S. Junagade ◽  
Anju Goyal
Keyword(s):  
Pharmacokinetic Parameters ◽  
Formulation Development ◽  
Duration Of Action ◽  
Drug Molecules ◽  
Carrier Molecule ◽  
Inflammatory Drugs ◽  
Development Approach ◽  
Pharmacologically Active ◽  
Mutual Prodrug ◽  
Poor Absorption

A clinically useful drug may have limitations in practice because of undesirable side effects, poor solubility, and poor bioavailability, short duration of action, first-pass effect, poor absorption & adverse effects. There are increased efforts in research to increase the therapeutic efficacy of drugs by eliminating or minimizing the undesirable properties of drug molecules. Some of the problems can be solved using a formulation development approach but in some cases, chemical modification in the molecule is necessary to correct the pharmacokinetic parameters. One of the approaches to convert the existing molecule to a more efficient molecule is prodrug design. Mutual Prodrug is the molecule in which an active drug molecule is attached to a carrier molecule having pharmacological activity. So a mutual prodrug consists of two pharmacologically active molecules connected by a bio labile linkage. Both molecules in this act as a pro moiety of each other. The design of mutual prodrug is very fruitful in the area of research & has given successful results in increasing the clinical & therapeutic effectiveness of the drugs. The present article takes a review of various applications of mutual prodrugs & development in this field in the last few decades.

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