Comparability Studies

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. 

Biosimilarity programs 

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 are experienced in method development, method transfer, method validation for tailored cell-based bioassay or potency assays for you’re your biologic and biosimilars products using cell migration, ligand binding, ELISA, cell signaling, cell proliferation and inhibition of proliferation, binding assays or competitive assays approaches.
We conduct physicochemical characterization programs to include determination of the composition, physical properties, and primary structure or higher order structure of the desired product. These include Molecular weight by mass spectrometry (High Resolution QToF or Orbitrap and MALDI-MS), isoform and impurity studies using electrophoresis and chromatography methods ( SDS-PAGE, cIEF, iCE, CE, UPLC) and Extinction coefficient determination and validation.

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.

 

Intertek conduct selective fragmentation of protein into discrete peptides by enzyme or chemical digestion followed by high-performance liquid chromatography and high resolution electrospray mass spectrometry 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 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  tests for free sulfhydryl groups.

 

Glycosylation studies are designed 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 or labelling prior to HILIC-Fluorescence, LC-MS, MALDI, HPAEC-PAD or GC-MSto provide the level of structural information required.
Our post-translational modification analysis experts apply a strategic approach to PTM analysis 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.

Our biologics characterisation group provides higher-order structure analysis via a suite of orthogonal techniques including Ccircular Ddichroism (CD), Diferential Scanning Calorimetry (DSC), Analytical Ultra-centrifugation (AUC), Size Exclusion Chromatography with Multi-Angle Light Scattering analysis (SEC-MALS), Nuclear Magnetic rResonance spectroscopy (NMR) and Iinfrared (FTIR) or Ffluorescence spectroscopy.

 

 
Need help or have a question? +1-858-558-2599
 

Need help or have a question?

+1-858-558-2599
EMEA UK:
+44 161 721 5247