Intertek is the industry leader with over 42,000 people in 1,000 locations in over 100 countries. Whether your business is local or global, we can ensure your products meet quality, health, environmental, safety, and social accountability standards for virtually any market around the world.
Monoclonal Antibody (mAb) Characterization and Analysis
Monoclonal antibody (mAb) development support including characterization, comparability, purity, structure, physicochemical properties, PTM, glycosylation and aggregation
The structure of mAbs are extremely complicated and dynamic and so it can be challenging to establish well-characterised antibody therapeutics to meet current regulatory expectations including the determination of the physicochemical and structural properties, purity, impurities and biologic activity, binding activity and quantity.
Our experts offer bespoke antibody analytics services, applying our experience, industry and regulatory knowledge (in particular EMA and ICH guidelines, Ph. Eur. Monographs) to design strategic packages pertinent to your actual need and phase of development from preclinical-phase characterisation studies through to Good Manufacturing Practice (cGMP) manufacture and beyond.
These analytics can be tailored to address your specific needs throughout the product lifecycle with a focus on monitoring relevant critical quality attributes (CQAs), demonstration that process changes do not impact physicochemical properties and structure, the presence of product-related impurities or process-related impurities.
We also offer support analytics to help you to demonstrate consistency or comparability of manufactured batches or as release tests for clinical trial materials or on-going GMP batch release tests. Our antibody product ICH Stability studies include forced degradation studies for identification of degradation products and development of stability indicating methods.
We continually invest in advanced analytical instrumentation which allows us to deliver data with the highest sensitivity, accuracy and resolution. Our experience spans recombinant monoclonal antibodies and related products such as biosimilars, fusion proteins, Fab-fragments and Fc fragments and antibody drug conjugates (ADCs). Our experts are ready to support your mAb product development and manufacture, helping you to meet all of your monoclonal antibody characterisation needs and according to the EMA and ICH guidelines.
The distribution of amino acids in the antibody product can be determined via a number of approaches. Our experts then perform sequencing studies using a broad range of enzymatic or chemical digestion with LC-MSMS mass spectrometry analysis.
Our comprehensive antibody characterization includes purification, isolation of intact antibodies or fragments. We perform selective fragmentation of protein into discrete peptides by enzyme or chemical digestion followed by electrospray mass spectrometry (ESI-MS) analysis and /or MALDI-TOF MS. Once the methodology is established we take the methods through validation and application in batch release or stability assessments.
Confirmation of the amino- and carboxy-terminal amino acids includes assessment of modifications of intact, heavy and light chains. This is performed by LC-MSMS to support product identification and establish homogeneity, where understanding the type and extent of modifications at either termini is a fundamental aspect of product quality control.
Where cysteine residues are present in the monoclonal antibody our scientists perform a qualitative/semi-quantitative assessment of the position and extent of expected and mismatched disulphide bridges by extended LC-MSMS peptide mapping studies, MALDI-TOF or Electrospray MS and colorimetric tests for free sulfhydryl groups.
Our post-translational modification analysis experts apply a strategic approach to PTM analysis (glycosylation, glycation, phosphorylation, deamidation, oxidation, carbamylation) during early development phases to help you to establish product acceptance criteria and as part of structural characterization studies and comparability programs, stability studies or quality control testing.
Antibodies contain carbohydrates; the percentage and location of the carbohydrate molecules differ according to the class of antibody. Glycosylation studies are designed to be product specific, however, these typically include determination of the levels of neutral and amino monosaccharides as well as sialic acids, assessment of glycoform distribution and glycan structure elucidation. Multiple technologies are applied in these determination including selective enzymatic cleavage and MALDI-TOF Mass spectrometry HPLC, HILIC, IEX or CE-LIF, to provide the level of structural information required.
Our biologics characterisation group provides higher-order structure of the monoclonal antibody via a suite of orthogonal techniques including circular dichroism (CD), nuclear magnetic resonance spectroscopy (NMR) and infrared (FTIR) or fluorescence spectroscopy.
Monoclonal antibodies commonly display several sources of heterogeneity due to molecular entities or variants or charged variants which lead to a complex purity/impurity profile. Our experts use a suite of orthogonal methods including molecular weight or size, isoform pattern, extinction coefficient, electrophoretic profiles, chromatographic data and spectroscopic profiles.
Aggregation can cause the formation of subvisible particles and may expose normally unexposed epitopes, leading to increased immunogenicity. Intertek’s laboratories determine the presence of aggregate species with characterisation using size exclusion chromatography (SEC), dynamic light scattering (DLS) amongst others.
Appearance (includes colour, clarity / opalescence), pH, particulates, turbidity, extractable volume, moisture, osmolality, sterility and bacterial endotoxins are assessed where appropriate. We monitor sub-visible and visible particulates in the drug product in the drug product, particularly for use in batch release and during stability studies.