Despite substantial efforts utilizing a diverse set of biologic evaluation and highthroughput
techniques to select candidates with the best chance of success in preclinical development, the vast majority of biologic drug molecules fail in clinical trials. With most biologic drugs, including gene therapies, failures are realized in late-stage development, after substantial investment has been made in a candidate. Here, we discuss the potential for improving identification of potentially successful biologic drugs and de-risking CMC and clinical designs earlier through strategic…

Host cell proteins (HCPs) are common impurities in biologic drug products and are an
obligatory critical quality attribute (CQA). The individual protein contaminants that make
up the HCP profile, however, may vary significantly among individual biologic products
and expression systems. As such, the HCP profile must be analyzed to identify even low
levels of potentially concerning species in a biologic drug to ensure safety and efficacy.
This whitepaper reviews fundamental aspects of HCPs pertaining to biologic drug
development and current and emerging…

The characterization of biopharmaceuticals such as new biological entities (NBEs) and their biosimilars is a challenging field due to their structural complexity. When implementing a manufacturing process, variations in the protein structure or post-translational modifications occur. Therefore, a characterization program is required according to the guidelines of national authorities. When characterizing proteins from scratch, glycosylation is a central modification that has to be taken into account, as it can affect the half-life and the stability of the protein.

• Development of an MS-based multi-attribute method (MAM) for monitoring
the product quality attributes (PQA) on a biotherapeutic protein IgG1
market product
• Characterization and quantification of PQAs: amino acid sequence,
terminal processing, truncation, deamidation, oxidation and glycosylation
• Introduction of a concept for full method qualification of a MAM approach
using reversed-phase chromatography in combination with high resolution
mass spectrometry
• Evaluation of the qualification parameters: analyte autosampler…

Developing and producing recombinant biopharmaceuticals in mammalian cells requires unambiguous monitoring of HCPs impurities. Immunoassays are still the method of choice for release testing, for which it is recommended to demonstrate the suitability of antisera in a QM-regulated environment to meet regulatory demands. However, peptide analysis by MS has been proven to be a powerful tool by providing complementary data for HCP characterization.

In the context of the production and development of biosimilar or new biological agents, it is necessary to analyze multiple samples of different process stages. Thereby differences to corresponding originator products as well as variances between the different samples must be viewed critically.
We present an optimization of MAM in IgG1 biosimilar development using Thermo Scientific Q Exactive HF-X instrumentation and the software solution (Protein Metrics Inc.) for fast processing of product quality attributes (PQAs) like post-translational modification levels, terminal variants and…

As a key element of biologic development today, precise characterizations of a drug candidate’s structures, post translational modifications (PTM’s) and determinations of its Critical Quality Attributes (CQA’s) are essential in defining, optimizing and controlling development programs from early candidate design through bioproduction scale-up, CMC package development, clinical trials, BLA submission and post-launch commercialization.

Developing and producing recombinant biopharmaceuticals in mammalian cells requires unambiguous monitoring of HCPs impurities. Immunoassays are still the method of choice for release testing, for which it is recommended to demonstrate the suitability of antisera in a QM-regulated environment to meet regulatory demands. However, peptide analysis by MS has been proven to be a powerful tool by providing complementary data for HCP characterization.

The development and production of recombinant biopharmaceuticals and their biosimilars
is a challenging field due to their structural complexity. While demonstrating batch to batch
comparability is a demanding analytical task, demonstrating biosimilarity is even more
challenging as it is already performed during early development with limited knowledge of
the structural features of the biosimilar candidate and limited molecule specific method
experience. Additionally analytical methods in biosimilar development need to be applied
for different aspects…

Developing and producing recombinant biopharmaceuticals in mammalian cells requires unambiguous monitoring of HCPs impurities. Immunoassays are still the method of choice
for release testing, for which it is recommended to demonstrate the suitability of antisera in a
QM-regulated environment to meet regulatory demands. However, peptide analysis by MS has been proven to be a powerful tool by providing complementary data for HCP characterization.