Analytical comparability study of recombinant monoclonal antibody therapeutics

Abstract

Process changes are inevitable in the life cycle of recombinant monoclonal antibody therapeutics. Products made using pre- and post-change processes are required to be comparable as demonstrated by comparability studies to qualify for continuous development and commercial supply. Establishment of comparability is a systematic process of gathering and evaluating data based on scientific understanding and clinical experience of the relationship between product quality attributes and their impact on safety and efficacy. This review summarizes the current understanding of various modifications of recombinant monoclonal antibodies. It further outlines the critical steps in designing and executing successful comparability studies to support process changes at different stages of a product's lifecycle.

High-throughput antibody screening from complex matrices using intact protein electrospray mass spectrometry

“…antibody screening | high throughput | intact protein mass spectrometry | electrospray U nambiguous characterization of analytes from complex matrices with high content information in a label-free format continues to expand the application of mass spectrometry (MS) in drug discovery (1)(2)(3). With the need for high accuracy, sensitivity, and selectivity, the rapidly improving MS instrumentations are emerging at the forefront of analyzing analytes with limited alternative assays for biologics developability (4)(5)(6), biotransformation, and high-throughput screening (HTS). For ultra-high-throughput screening, matrix-assisted laser desorption/ionization (MALDI) is amenable to speeds >100,000 samples per day (7)(8)(9)(10)(11).…”

Preparing Proteoforms of Therapeutic Proteins for Top-Down Mass Spectrometry

“…More details about sources and effects of microheterogeneity are described in the excellent reviews of Beyer [36] and Ambrogelly [37].…”

“…Liquid chromatography (LC) is the most common for purification and fractionation of therapeutic proteins [37]. The proteoforms are either separated by sizeexclusion (SEC), making use of different path lengths through chromatographic particles related to the size of the proteins, or by adsorption chromatography.…”

Synthetic sRNA‐Based Engineering of Escherichia coli for Enhanced Production of Full‐Length Immunoglobulin G

“…[ 15 ] Although aglycosylated IgG cannot induce complement‐dependent cytotoxicity and antibody‐dependent cell‐mediated cytotoxicity owing to the lack of a glycan, [ 16,17 ] they were not found to induce any adverse health effects such as immunogenicity, and as stable as glycosylated mAbs. [ 18,19 ] Tolerx (MA, USA) produced a series of humanized aglycosylated antibodies, including TRX1, [ 20 ] TRX4, [ 21 ] and TRX518, [ 22 ] through the N297A mutation, which have completed the phase I clinical trials. Genetech has developed a monovalent aglycosylated antibody (onartuzumab) in E. coli for the treatment of lung cancer and has entered the phase II clinical setting in USA.…”