Comparability studies according to ICH Q5E covering physiochemical, structure and biologic potency characterization of a range of biological products
Comparability studies are key to ensuring that a manufacturing process change will not have an adverse impact on the quality, safety (eg: immunogenicity) or efficacy of the biotechnological or biopharmaceutical product.
Under the principals of the ICH Q5E Comparability of Biotechnological/Biological Products guideline, comparability studies should provide analytical confirmation that your drug substance or drug product has highly similar quality attributes before and after manufacturing process changes. Changes to manufacturing processes of products can be necessary during development and after approval, perhaps due to driving improvements in scale, product quality or product stability. Changes to processes can also be necessary to respond to changes in regulatory requirements.
We are highly experienced in comparability studies conducted to Good Laboratory Practice (GLP) or Good Manufacturing Practice (cGMP) standards for biosimilars, monoclonal antibodies and recombinant proteins.
Our biologics comparability team design bespoke analytical programes that ensure that the relevant quality attributes for your drug substance or drug product are evaluated to support your manufacturing process changes. We select analytics referenced by the ICH Q6B Guideline to carefully examine the product from all aspects including structural features including primary, secondary and higher order structure and assessment of post-translational modifications (PTM), physicochemical properties, biological activity /potency and immunogenicity in order to demonstrate that modifications did not occur which may adversely impact the safety and efficacy of the drug. We also assess purity / impurity profiles and can conduct comparability to Good Laboratory Practice (GLP) or Good Manufacturing Practice (cGMP) standards.
Based on many years of experience, our strategic approach to comparability programs means that we select from many different analytical techniques to deliver highly relevant comparability studies for proteins, antibodies, biosimilars, antibody-drug conjugates, oligonucleotides and other biologic products.
Our teams provide analytical programs to demonstrating biosimilarity to a reference product which allow highly relevant early stage characterisation and later stage comparative data. These programs evaluate and compare all pertinent features of the biosimilar product and are based on the criteria outlined in ICH Q6B.
As your comparability outsourcing service provider, we apply our knowledge of detailed analytics to evaluate the key quality attributes of your drug substance or drug product to help you ensure that manufacturing process changes do not impact product quality, efficacy or safety. Across your product’s lifecycle, from early stage through to later-phase development, CMC requirements and ongoing production, we apply our Total Quality Assurance expertise to meet your comparability study needs in line with the latest regulatory requirements.
We apply a number of approaches to initially quantitate the distribution of amino acids (Amino Acid Analysis). This is then accompanied by sequencing or peptide mapping using a broad range of enzymatic or chemical digestion followed by LC-MSMS analysis.
Confirmation of the amino- and carboxy-terminal amino acids is performed by LC-MSMS specifically with the aims of product identification and to 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 molecule, 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 Ellman's test
free sulfhydryl groups.
Our biologics characterisation group provides higher-order structure analysis via a suite
of orthogonal techniques including
(CD), Diferential Scanning Calorimetry (DSC), Analytical Ultra-centrifugation
(AUC), Size Exclusion Chromatography with Multi-Angle Light Scattering analysis
(SEC-MALS), uclear agnetic
spectroscopy (NMR) and infrared
(FTIR) or fluorescence
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