Biosimilars

Biosimilars

Perform rapid and robust biotherapeutic analysis of biosimilar candidates with Waters advanced analytical technologies. Waters columns, consumables, instrumentation, and informatics deliver a complete platform to confidently establish the comparability of a therapeutic drug candidate to the reference product molecule.

Perform rapid and robust biotherapeutic analysis of biosimilar candidates with Waters advanced analytical technologies. Waters columns, consumables, instrumentation, and informatics deliver a complete platform to confidently establish the comparability of a therapeutic drug candidate to the reference product molecule.
Ensure viral vector quality with Waters LC and MS solutions for characterization and routine analysis.
Ensure viral vector quality with Waters LC and MS solutions for characterization and routine analysis.

Overview

Global regulatory bodies require sufficient analytical and biological evidence of comparability between reference product and biosimilar candidates. Labs must characterize multiple batches of proteins to establish the biosimilarity of a therapeutic drug candidate to the original reference product molecule.

Waters integrated solutions provide a comprehensive platform for streamlined and robust analysis of the product attributes of biosimilars and their reference products, including:

  • Primary structures, such as amino acid sequence 
  • Higher order structures, including secondary, tertiary, and quaternary structure (including aggregation)
  • Post-translational modifications, such as glycosylation, phosphorylation, deamidation, and oxidation
  • Intentional chemical modifications, such as PEGylation sites and characteristics

Partner with Waters to support therapeutic safety and efficacy and improve patient health by confidently establishing comparability of biosimilar products.

Applications

Due to the complex nature of biotherapeutics, biosimilar developers need to demonstrate comprehensive characterization, process robustness, and should have the ability to monitor product and critical quality attributes. Intact mass and subunit analyses are performed to confirm molecular mass and detect sequence errors or PTMs, providing a comparison of relative abundance of major variants, demonstrating a basic level of similarity and identifying major differences for further study.

Due to the complex nature of biotherapeutics, biosimilar developers need to demonstrate comprehensive characterization, process robustness, and should have the ability to monitor product and critical quality attributes. Intact mass and subunit analyses are performed to confirm molecular mass and detect sequence errors or PTMs, providing a comparison of relative abundance of major variants, demonstrating a basic level of similarity and identifying major differences for further study.

Application Notes

Comprehensive tools for intact protein analysis

The levels of self-associated, aggregated, and fragmented size-variant impurities in therapeutic proteins, such as biosimilars, are regarded as critical quality attributes (CQA) throughout pre-clinical and clinical studies, as well as in approved drug products, due to their potentially harmful impact on immunogenic response or activity. Size exclusion chromatography (SEC), often coupled to multiangle light scattering (MALS) and UV detection, is a common method deployed to monitor these impurities.

The levels of self-associated, aggregated, and fragmented size-variant impurities in therapeutic proteins, such as biosimilars, are regarded as critical quality attributes (CQA) throughout pre-clinical and clinical studies, as well as in approved drug products, due to their potentially harmful impact on immunogenic response or activity. Size exclusion chromatography (SEC), often coupled to multiangle light scattering (MALS) and UV detection, is a common method deployed to monitor these impurities.

Application Notes

Superior size-based separations

Peptide mapping is an important technique to show comparable therapeutic profiles between reference product drugs and biosimilars. High peptide mapping coverage demonstrates similarity in the amino acid sequence of a biosimilar, highlighting errors in cloning or expression. Modifications such as oxidation and deamidation impact drug safety and efficacy and can also be quantitatively monitored at the peptide level. Non-reducing digests can be used to analyze disulfide linkages and prove equivalence to innovators. Waters solutions enable measurement of the important attributes of protein-based drugs that enable rapid decision-making for product development, manufacturing, and release.

Peptide mapping is an important technique to show comparable therapeutic profiles between reference product drugs and biosimilars. High peptide mapping coverage demonstrates similarity in the amino acid sequence of a biosimilar, highlighting errors in cloning or expression. Modifications such as oxidation and deamidation impact drug safety and efficacy and can also be quantitatively monitored at the peptide level. Non-reducing digests can be used to analyze disulfide linkages and prove equivalence to innovators. Waters solutions enable measurement of the important attributes of protein-based drugs that enable rapid decision-making for product development, manufacturing, and release.

Application Notes

Workflows to streamline comparability studies at the peptide level

Glycosylation significantly influences the properties of therapeutic proteins, including efficacy and immunogenicity. By understanding and controlling glycosylation patterns, biosimilar developers can demonstrate equivalent product quality and consistency during manufacturing.

Ensuring that biosimilars are equivalent to innovator drugs in terms of glycosylation is crucial for regulatory approval and patient safety. Waters provide market leading tools for analysis of glycopeptides and released N-glycans, providing an accurate picture of differences in major and minor glycoforms to assess acceptable differences for process control and comparability.

Glycosylation significantly influences the properties of therapeutic proteins, including efficacy and immunogenicity. By understanding and controlling glycosylation patterns, biosimilar developers can demonstrate equivalent product quality and consistency during manufacturing.

Ensuring that biosimilars are equivalent to innovator drugs in terms of glycosylation is crucial for regulatory approval and patient safety. Waters provide market leading tools for analysis of glycopeptides and released N-glycans, providing an accurate picture of differences in major and minor glycoforms to assess acceptable differences for process control and comparability.

Application Notes

Develop robust and comparable processes by monitoring profiles of glycopeptides and released N-glycans

Protein higher order structure is a key indicator of equivalence between biosimilars and reference drugs. Techniques such as HDX-MS or Collision Induced Unfolding (CIU) measure a protein’s conformational dynamics and stability, which can be compared to reference products to reveal functional differences or demonstrate acceptable similarity. Waters comprehensive structural biology solutions provide chromatographic accuracy, sample management and powerful mass spectrometry tools to acquire and process these complex data sets.

Protein higher order structure is a key indicator of equivalence between biosimilars and reference drugs. Techniques such as HDX-MS or Collision Induced Unfolding (CIU) measure a protein’s conformational dynamics and stability, which can be compared to reference products to reveal functional differences or demonstrate acceptable similarity. Waters comprehensive structural biology solutions provide chromatographic accuracy, sample management and powerful mass spectrometry tools to acquire and process these complex data sets.

Application Notes

Demonstrate comparability of protein higher order structure with HDX-MS

Webinar: Deploying Waters Solutions to Enhance Biosimilar Development

Hear a customer perspective on deploying Waters solutions to enhance biosimilar development with this webinar on the streamlined mAb subunit LC-MS workflow for multiple attribute monitoring (MAM) of biosimilar mAb candidates during bioprocessing and development with Jared Young from Similis Bio.

Hear a customer perspective on deploying Waters solutions to enhance biosimilar development with this webinar on the streamlined mAb subunit LC-MS workflow for multiple attribute monitoring (MAM) of biosimilar mAb candidates during bioprocessing and development with Jared Young from Similis Bio.
View Webinar
Preparative separations are purposeful and practical, meant for isolating targets from mixtures.

Solutions

With Waters systems, characterize complex biosimilars in less time and with greater confidence.

With Waters systems, characterize complex biosimilars in less time and with greater confidence.

Efficient product attribute monitoring of biosimilars

Efficient product attribute monitoring of biosimilars
BioAccord LC-MS System

Enable biosimilar comparability analyses in every lab with the Waters BioAccord LC-MS System, and waters_connect software for compliance-ready data analysis and reporting.

  • Intact Structure and Variability
  • Sequence and Modifications
  • Quality, Efficacy and Immunogenicity
  • Aggregation and Fragment Impurity Analysis

Complete high-resolution capability for confident characterization and method transfer

Complete high-resolution capability for confident characterization and method transfer
Xevo G3 QTof

Accelerate biosimilar characterization and monitoring with the Xevo G3 QTof high-performance HRMS benchtop system, delivering accurate qualitative and quantitative results.

  • Intact Structure and Variability
  • Sequence and Modifications
  • Quality, Efficacy and Immunogenicity
  • Aggregation and Fragment Impurity Analysis
  • Higher Order Structure

Delivering cutting-edge analytical performance

Delivering cutting-edge analytical performance
SYNAPT XS High Resolution Mass Spectrometer

Obtain ultimate flexibility with the SYNAPT XS mass spectrometer that offers greater freedom of analytical choice to support scientific creativity and technical success for analysis of biosimilars.

  • Intact Structure and Variability
  • Sequence and Modifications
  • Quality, Efficacy and Immunogenicity
  • Aggregation and Fragment Impurity Analysis
  • Higher Order Structure

Ultimate power, ultimate performance. Redefine the boundaries of science

Ultimate power, ultimate performance. Redefine the boundaries of science
SELECT SERIES Cyclic IMS

Combine novel cyclic ion mobility separation with state-of-the-art high-performance, time-of-flight mass spectrometry with the SELECT SERIES Cyclic IMS, enabling researchers to reliably identify and monitor biosimilar attributes

  • Intact Structure and Variability
  • Sequence and Modifications
  • Quality, Efficacy and Immunogenicity
  • Aggregation and Fragment Impurity Analysis
  • Higher Order Structure

Uniquely versatile detector for every developmental stage

Uniquely versatile detector for every developmental stage
DAWN

The DAWNTM MALS detector assists at every development stage. Couple with EclipseTM to measure binding affinity during discovery. Place downstream of any LC and perform advance analysis of biosimilar protein-conjugate ratio, post-translational modifications, and aggregation.

  • Intact Structure and Variability
  • Sequence and Modifications
  • Quality, Efficacy and Immunogenicity

Compliance-ready, networkable applications-based software to streamline LC-MS data acquisition, processing, and reporting.

Compliance-ready, networkable applications-based software to streamline LC-MS data acquisition, processing, and reporting.

Biosimilar analysis workflows

Biosimilar analysis workflows
waters_connect for biopharmaceuticals

Streamline biosimilar analysis workflows and unite LC-MS systems across organizations with waters_connect for biopharmaceuticals, a compliant-ready, networked informatics platform.

  • Intact Structure and Variability
  • Sequence and Modifications
  • Quality, Efficacy and Immunogenicity
  • Aggregation and Fragment Impurity Analysis

Achieve high efficiency separations for  the analysis and purification of biosimilars including size-exclusion chromatography for aggregation, reversed-phase for intact, subunit, peptide mapping, ion exchange for charge variants, and hydrophilic chromatography for glycoprotein analysis.

Achieve high efficiency separations for  the analysis and purification of biosimilars including size-exclusion chromatography for aggregation, reversed-phase for intact, subunit, peptide mapping, ion exchange for charge variants, and hydrophilic chromatography for glycoprotein analysis.

Innovative solutions for biosimilar characterizations for charge variant and intact and subunit analyses

Innovative solutions for biosimilar characterizations for charge variant and intact and subunit analyses
BioResolve Columns and Consumables

BioResolve RP mAb Polyphenyl  Columns provide improved peak capacity and minimal carry-over for intact and subunit analysis of proteins and mAbs specifically QC-tested with a NIST-based, mAb subunit standard. BioResolve SCX mAb Columns and Buffers reliably separate charge variants for a wide range of mAbs using optical or LC-MS compatible mobile phases.

  • Intact Structure and Variability
  • Sequence and Modifications
  • Quality, Efficacy and Immunogenicity

More confident size variant separations for biosimilars

More confident size variant separations for biosimilars
ACQUITY and XBridge Premier Protein SEC 250 Å Columns

Minimize secondary ionic or hydrophobic interactions in size-based separations with ACQUITY and XBridge Premier Protein SEC 250 Å Columns with MaxPeak High Performance Surface (HPS) Technology for reliable protein aggregate, monomer, and fragment analyses using a “platform” type method with 30% increase in resolution.

  • Intact Structure and Variability
  • Sequence and Modifications
  • Quality, Efficacy and Immunogenicity

Maximize sensitivity while minimizing metal adsorption of acidic deamidated peptides

Maximize sensitivity while minimizing metal adsorption of acidic deamidated peptides
MaxPeak Premier Peptide Columns

Gain enhanced recovery and sensitivity for acidic peptides with Waters ACQUITY, XSelect, and XBridge Premier Peptide Columns that are QC batch-tested with Waters Cytochrome c Digest Standard for increased column-to-column performance consistency.

  • Intact Structure and Variability
  • Sequence and Modifications
  • Quality, Efficacy and Immunogenicity

Achieve quick, clean and complete protein digestion

Achieve quick, clean and complete protein digestion
RapiZyme Trypsin, Mass Spectrometry (MS) Grade

Achieve quick, clean, and complete mAb and biosimilar digestions in just 30 minutes with RapiZyme Trypsin, Mass Spectrometry (MS) Grade, a highly activie autolysis-resistant enzyme that reduces the likelihood of artificial modifications occurring during sample preparation prior to LC-MS analysis.

  • Sequence and Modifications
  • Protein Digestion
  • Peptide Mapping
  • Tryptic Digestion
  • Quality, Efficacy and Immunogenicity

Streamline peptide mapping sample preparation

Streamline peptide mapping sample preparation
PeptideWorks Tryptic Protein Digestion Kits

Achieve high efficiency, reproducible peptide maps in under 2.5 hours with PeptideWorks Tryptic Protein Digestion Kits for manual or automated workflows that are 4x faster than average home-brew methods and provide a 78% reduction in missed cleavages.

  • Sequence and Modifications
  • Protein Digestion
  • Peptide Mapping
  • Tryptic Digestion
  • Quality, Efficacy and Immunogenicity

Gain control over your glycan separations

Gain control over your glycan separations
MaxPeak Premier Glycan Columns

Obtain fast, high resolution glycan identification for your biosimilars with Waters complete line of glycan columns to analyze glycoproteins, glycopeptides and released N-glycans with exceptional reproducibility.

  • Intact Structure and Variability
  • Sequence and Modifications
  • Quality, Efficacy and Immunogenicity

Rapid, sensitive, and easy detection of N-glycans

Rapid, sensitive, and easy detection of N-glycans
GlycoWorks RapiFluor-MS Released N-Glycan Kits

Achieve unprecedented fluorescent and mass spectrometric performance for glycan detection with GlycoWorks N-glycan Kits that improve the throughput of N-glycan sample preparation so you don’t have to compromise between speed and sensitivity.

  • Intact Structure and Variability
  • Sequence and Modifications
  • Quality, Efficacy and Immunogenicity

Faster, more efficient online protein digestion in HDX-MS workflows

Faster, more efficient online protein digestion in HDX-MS workflows
Enzymate BEH Pepsin Column

Fast, efficient, and reproducible online pepsin digestion is critical in experiments that require more peptide coverage. With the Waters Enzymate BEH Pepsin Column, you can easily incorporate online protein digestion into existing HDX- MS workflows. The Enzymate BEH Pepsin Column efficiently digests intact proteins into peptides in an online HDX system, typically in about 30 seconds.

  • Sequence and Modifications
  • Quality, Efficacy and Immunogenicity

Gain efficiency and walk away time with verified lab automation solutions.

Gain efficiency and walk away time with verified lab automation solutions.

Enhance sample prep efficiency and throughput

Enhance sample prep efficiency and throughput
Laboratory Automation and Equipment

Streamline sample preparation for LC-MS analyses with Waters Laboratory Automation and Equipment that deliver verified workflows to help minimize variability, improve traceability, and simplify method transfer.

  • Sequence and Modifications
  • Efficacy and Immunogenicity
  • Quality, Efficacy and Immunogenicity

Achieve testing efficiencies and accurate results using streamlined Waters services and support.

Achieve testing efficiencies and accurate results using streamlined Waters services and support.

Your success is just a click away

Your success is just a click away
Waters Global Services

Optimize your laboratory's productivity and success with Waters Global Services to maintain peak system performance, minimize downtime, address application challenges, and support stringent compliance requirements.

  • Sequence and Modifications
  • Intact Structure and Variability
  • Quality, Efficacy and Immunogenicity

Make science more accessible with Waters Capital

Make science more accessible with Waters Capital
Payment Solutions

Maximize resources and minimize risk with payment options from Waters Capital, including upgrading aging equipment, getting customized support, and bundling services into one monthly payment.

  • Sequence and Modifications
  • Intact Structure and Variability
  • Quality, Efficacy and Immunogenicity

The data speaks for itself

The data speaks for itself
Peptide MAM: Mirror plots showing the comparison of Inflectra to Remicade for both (left) unstressed samples and (right) samples subjected to two weeks of elevated temperature stress.
Peptide MAM: Mirror plots showing the comparison of Inflectra to Remicade for both (left) unstressed samples and (right) samples subjected to two weeks of elevated temperature stress.
Peptide MAM: Selected product quality attributes for Remicade (infliximab) and three biosimilars subjected to thermal stress, T0, T1 (1 week), and T2 (2 weeks). Injections 1–3=Remicade (infliximab), 4–6=Inflectra (infliximab), 7–9=Avsola (infliximab), and 10–12=Renflexis (infliximab).
Peptide MAM: Selected product quality attributes for Remicade (infliximab) and three biosimilars subjected to thermal stress, T0, T1 (1 week), and T2 (2 weeks). Injections 1–3=Remicade (infliximab), 4–6=Inflectra (infliximab), 7–9=Avsola (infliximab), and 10–12=Renflexis (infliximab).
Mirror plots comparing an innovator infliximab sample (Remicade) to two biosimilar samples, (left) Inflectra and (right) Renflexis. The difference in peak intensity is shown as an overlay on each plot, and the Venn diagrams indicate the number of identified glycoforms unique to each sample and those present in both samples
Mirror plots comparing an innovator infliximab sample (Remicade) to two biosimilar samples, (left) Inflectra and (right) Renflexis. The difference in peak intensity is shown as an overlay on each plot, and the Venn diagrams indicate the number of identified glycoforms unique to each sample and those present in both samples.
Overlaid TIC chromatograms of an infliximab originator (Remicade) and a biosimilar (Renflexis) released N-glycan analysis. Some of the glycans differing between the two samples, either in presence or relative abundance, are indicated in the chromatogram with their structures
Overlaid TIC chromatograms of an infliximab originator (Remicade) and a biosimilar (Renflexis) released N-glycan analysis. Some of the glycans differing between the two samples, either in presence or relative abundance, are indicated in the chromatogram with their structures.
Stacked plots of SEC separations on selected columns for biosimilar mAb sample using 1X Dulbecco’s phosphate buffer saline as a mobile phase are shown.
Stacked plots of SEC separations on selected columns for biosimilar mAb sample using 1X Dulbecco’s phosphate buffer saline as a mobile phase are shown.

Webinars and Resources

  • Blog

How Analytical Technologies Support the Development of Biosimilar Drugs

How Analytical Technologies Support the Development of Biosimilar Drugs
Download
  • Brochure

BioAccord LC-MS System with ACQUITY Premier

BioAccord LC-MS System with ACQUITY Premier
Download
  • Infographic

Protein and Peptide Attribute Monitoring Workflows

Protein and Peptide Attribute Monitoring Workflows
Download

Related

Intact Protein Analysis
Protein molecular weight must be quickly confirmed, along with glycoform heterogeneity determination. Waters technologies deliver quick, accurate protein molecular weights for confirmation and determination of intact proteins.

Peptide Mapping
Achieve unmatched resolution of complicated protein digests, exceptional glycopeptide resolution, and shorter analysis times with UPLC separations and optimally selective and resolving peptide separation chemistries.

Glycan Solutions
Improve the quality of your glycan structure analysis results with Waters complete and easy-to-use workflows for analyzing glycans and glycoproteins.

Hydrogen Deuterium Exchange - Mass Spectrometry
Answers for all of your structural questions for biotherapeutics, complexes, and protein folding/stabillity studies. Waters offers unrivaled instrumentation, chemistries, informatics, and training programs.

Learn more about Biosimilars Solutions.

Learn more about Biosimilars Solutions.
Ensure viral vector quality with Waters LC and MS solutions for characterization and routine analysis.
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