Leveraging the Power of Advanced Mass Spectrometry to Fulfil IND, IMPD and BLA Filings

Power of Advanced Mass Spectrometry

Mass Spectrometry (MS) is one of the most powerful analytical techniques available for protein characterization. MS can provide data on the quantity, structural integrity and post-translational modifications of proteins. MS techniques have broad applicability for characterizing biopharmaceuticals, such as identifying post-translation modifications and structural characterization of biopharmaceutical proteins, product identification, comparability, biosimilarity, and quantifying host-cell protein impurities.

Because MS can characterize an array of product quality attributes, including molecular weight, primary amino acid sequence, post translation and chemical modifications, the technique is invaluable across the lifecycle of a biopharmaceutical product. For an IND/IMPD filing, routine analysis such as intact mass and a peptide map LC/MS/MS analysis can provide the basis of the elucidation of structure for IND/IMPD filings. At FUJIFILM Diosynth Biotechnologies (FDB), we partner with our clients to help ensure they have the right product characterization data they need for timely regulatory filings.

Technological advances in MS instrumentation have facilitated a dramatic increase in the number of areas where MS data can support a BLA filing such as host cell protein characterization and clearance, higher order structure (HOS), biosimilar comparability, glycosylation profiling and sequence variant analysis. As part of our services, we generate submission reports for our clients’ regulatory filings.

With emerging techniques such as Multi-Attribute Mapping (MAM) for development and QC release, structural characterization using hydrogen-deuterium MS (HDX) and ion mobility MS, mass spectrometry will continue to grow as one of the leading protein identification and characterization techniques within the biopharmaceutical BLA filings. A 2017 FDA study reported that 99% of BLAs filed between 2000 and 2015 contained some MS based data[i]. Furthermore, intact MS, peptide mapping-based LC/MS identity testing and MAM methods are now routinely used in GMP compliant QC labs for commercial release and stability testing of a biotherapeutic. Having completed a recent expansion of our MS instrumentation, FDB offers unparalleled CDMO capabilities for mass spectrometric based structural characterization and cGMP release testing.

Liquid chromatography/mass spectrometry methodologies have broad applicability for the identification and quantification of impurities resulting from the biologics manufacturing process which may include cell substrates (e.g., host cell proteins), fermentation or cell culture expression (e.g., inducers, antibiotics, or media components), chromatographic media used during purification, detergents used for viral inactivation and buffer components. The superior sensitivity and specificity of tandem MS allows for the detection and demonstration of the clearance of process residuals achieving sensitivity into the ppb range.

Our Experience

Our expert team of mass spectrometry scientists has decades of experience having trained in world class university laboratories and the experience gained from characterization of hundreds of molecules that FDB has supported including:

• Monoclonal antibodies (mAbs, domain antibodies, fragments)
• Fusion proteins
• Enzymes
• PEGylated proteins
• Glycoproteins
• Biosimilars
• VLPs
• Bispecific antibodies & engineered proteins
• Protein based vaccines
• Host cell proteins
• Process residuals

Our Capabilities

• Primary sequence verification and post translation modification identification
• Cell line developability
• Structural characterization
• Glycan characterization and identification
• Sequence variant identification
• Host cell protein characterization and quantitation
• Multi-Attribute-Mapping
• Intact, subunit, peptide map cGMP release testing
• Elucidation of structure data packages for IND/IMPD and BLA/MAA filing
• PEGylation/conjugation site and occupancy analysis
• Characterization support for process development, process characterization, formulation development and forced degradation
• Process Residual cGMP testing
• Impurity characterization

Our Instrumentation

• Waters Select Series Cyclic IMS with Electron Capture Dissociation (ECD)detection
• Sciex ZenoTOF 7600 with SWATH and Electron activated dissociation (EAD) detection
• Thermo Scientific Orbitrap Exploris 240
• Waters Xevo^® G2 QTof
• Waters Xevo^® G2-XS QTof
• Waters ACQUITY Premier BioAccord
• Waters Xevo TQ-S micro Triple Quadrupole MS
• Waters Acquity Premier UPLC
• Waters Agilent 1260/1290 UPLC
• Waters Acquity M-Class UPLC
• 908 Devices ZipChip CE-ESI mass spectrometry system

Our Software

• Protein Metrics Biosphere™
• WatersConnect, Waters UNIFI, MassLynx™, BiopharmaLynx™, TargetLynx™, Progenesis QI
• ThermoScientific BioPharma Finder™
• Sciex BioPharmaView™, ProteinPilot™

Our expertise and capabilities provide unparalleled mass spectrometric services covering initial developability and structural characterization to support IND/IMPD filings. We offer orthogonal host cell protein evaluation through comprehensive characterization in support of BLA/MAA licensure. These critical services can support and advance key milestones in your product development and commercialization efforts by providing in-depth product characterization data.

We recently announced the investment and expansion of our development and Quality Control Laboratories in Research Triangle Park, NC and Billingham, UK. We are very proud of what this means to us as an organization and the customers we serve in their advancement of medicines and therapies. Having completed a recent expansion of our MS instrumentation, FDB offers unparalleled CDMO capabilities for mass spectrometric based structural characterization and cGMP release testing.

[i] Rogstad, S. et al, A Retrospective Evaluation of the Use of Mass Spectrometry in FDA Biologics License Applications, Journal of The American Society for Mass Spectrometry, https://link.springer.com/article/10.1007/s13361-016-1531-9, [Access May 15, 2022]