QUALITY CONTROL OF BIOLOGICS AND BIOSIMILARS

Kymos is an EMA and FDA inspected CRO providing quality control of biologics and biosimilars being listed among the Top 10 global vendors of biosimilar testing services. Our GLP- and GMP-compliant CMC assays target very different clients, from global biosimilar manufacturers, bioprocessing facilities, API manufacturers and fill & finish plants to smaller innovator biotech firms. Working with biopharmaceuticals calls for an integrated orthogonal approach using multiple techniques to fully understand the analytical fingerprint of such complex molecules. For this reason, our success relies heavily on our experience with a wide range of biologics such as:

  • Innovative proteins and innovative mAbs
  • Biosimilars (proteins and mAbs)
  • Therapeutic peptides: innovative, generic and hybrid formulations
  • Hormones: GSF, FSH, LH, hCG, GCG, GLP1, GH, TSH
  • Monoclonal antibodies (mAbs)
  • Interferons, insulins and coagulation factors
  • Filgrastim and PEG-Filgrastim
  • Toxins: Natural, recombinant and innovative
  • Antibody drug conjugates (ADC)
  • Vaccines: Non-living and recombinant
  • Heparins and glycosaminoglycans: Unfractionated and Low-molecular-weight (LMWH)

Kymos is among the few CROs to provide complex characterizations of innovative biologics, biosimilarity assessments and routine batch testing and release for biopharmaceuticals. We combine an important pool of instruments, an inclusive list of prequalified methods and the capacity to develop customized projects for our clients. Our CMC services for biopharmaceuticals can be grouped in the following chapters:

• Routine quality control of biologics
• Characterization of new biologics
Comparability studies (aka biosimilarity assessments)
Batch testing and batch release of biologics

Pharmaceutical Laboratory
Capillary Electrophoresis Beckman PA800S

ROUTINE QUALITY CONTROL OF BIOLOGICS

Kymos provides GMP-certified quality control for biologics and biosimilars such as raw materials, APIs, excipients, intermediates, IMPs, finished products, packaging materials, manufacturing equipment and process environment samples according to customer specifications or relevant pharmacopoeia (EP, USP, BP, JP). Non-compendial methods can also be transferred, validated or developed de novo, and for Quality Control purposes we work under approved Quality Agreements and issue GMP Certificates of Analysis (CoAs) signed by our QPs. These assays target manufacturers of biologic substances and products in need of outsourcing specific techniques, non-routine tests as well as routine batch testing and release. Quality control involves multiple disciplines:

  • Identification test (IEF, IEX-HPLC, ELISA, peptide mapping, glycosylation profile ciIEF)
  • Appearance (color, clarity)
  • Assay (ELISA, SEC-HPLC, RP-HPLC) and dosage uniformity
  • Purity (CE-SDS -reduced and non-reduced, SEC-HPLC, RP-HPLC)
  • Protein Content (UV, 280nm, Bradford, BCA, Lowry)
  • Dosage of excipients (HPLC)
  • Physical determinations (pH, osmolality)
  • Moisture (Karl Fisher)
  • Residual solvents (volatile organic compounds, organic volatile impurities)
  • Impurities identification (HPLC/UHPLC, LC-MS, GC-MS)
  • Process related Impurities determination (ELISA, RT-qPCR)
  • Elemental impurities (AAS, ICP/MS)
  • Nitrosamine impurities (LC-MS-MS, HS-GC-MS)
  • Particulate matter (visible and subvisible particles)
  • Extractables & Leachables
  • Enzymatic and chromogenic tests (heparins and others)
  • Determination of enzyme activity (learn more here)
  • Biological potency assays (CBA, ELISA, flow cytometry)
  • Extractable volume
  • Physical properties of injection devices (glide and brake force for syringes)
  • Other CMC tests with specific departments
Laboratory analytist with pipette
Quality Control

CHARACTERIZATION OF NEW BIOLOGICS

Characterization of a biotechnological or biological product according to the ICH Q6B guideline includes determination of its physicochemical properties, biological activity, immunochemical properties, purity, and impurities using appropriate techniques to ensure safety, quality and efficacy. The number and nature of required assays is determined from the list below on a case-by-case basis:

Comparability studies (aka biosimilarity assessments)

We follow a step-by-step comparability model for biosimilar drugs focused on critical quality attributes (CQAs), identified and classified according to their risk ranking. The number and nature of required assays is determined from the list below on a case-by-case basis:

Laboratory analytist
GENERAL ANALYTICAL TECHNIQUESSTRUCTURAL ANALYSIS
A preliminary overview of the quality attributes of the molecule during initial development phases:

  • Electrophoresis (PAGE, SDS-PAGE, Bioanalyzer, IEF)
  • Western Blot
  • Extinction Coefficient, Bradford, Lowry, BCA (total protein quantitation)
  • HPLC AccQ-Tag® (Waters) and OPA® (Agilent) for amino-acid analysis
  • Sulfide quantitation by Ellman method
  • Antibody isotyping
Full molecular identification for strain selection, bioprocess and final product characterization:

  • Intact protein mass (Electrospray MS, MALDI-TOF)
  • Peptide mapping, amino acid sequencing (LC-UV-MS/MS, QTof, QTRAP)
  • N and C terminal sequencing of intact protein (MALDI-TOF and Edman degradation)
  • Glycosylation and phosphorylation sites (LC-UV-MS)
  • Glycosylation Profiles (GC, LC, MS/MS, capillary electrophoresis)
  • Monosaccharide profile (LC and GC)

CONFORMATIONAL ANALYSIS

IDENTITY, CONTENT, PROTEIN IMPURITIES

Protein folding and 3D conformation determine biological activity and immunogenicity:

  • Circular Dichroism (CD)
  • Ultraviolet spectroscopy (UV)
  • Fluorescence spectroscopy (FL)
  • Infrared spectroscopy (FTIR)
Chromatographic patterns are quality indicators of the purification process:

  • Liquid chromatographic patterns (RP-; SEC-; Ion Exchange-; and Affinity-HPLC/UPLC plus LC-UV-MS)
  • Capillary electrophoresis (reduced and non-reduced)
  • Imaged capillary isoelectric focusing (icIEF)
  • ELISA, ECLA, RIA

PROCESS-RELATED IMPURITIES

BIOLOGICAL ACTIVITY

Other quality indicators of the purification process and also linked to safety concerns:

  •  Host Cell Proteins (specific ELISA)
  •  Chemical contaminants (HPLC, GC)
  • Elemental impurities (AAS, ICP-MS)
  • Nitrosamine impurities (LC-MS/MS, HS-GC-MS)
  • DNA (qPCR and colorimetric commercial kits)
  • Mycoplasma (PCR commercial kits)
  • Endotoxins (colorimetric or gel-clot test)
  • Bioburden
Biological tests to confirm molecule activity:

  • Binding studies (ELISA, ECLA, RIA, SPR Biacore®)
  • Potency assays (Cell –based assays)
  • Competitive inhibition ELISA assays for vaccines

Kymos offers GMP-certified importation, batch testing and batch release services. We have several QPs and are certified importers and manufacturers for quality control of human, veterinary and investigational medicinal products (IMPs), with capabilities to test and release sterile, non-sterile products and high potency active ingredients (HAPI). Our integrated solution includes:

  • Analytical method transfer (AMT)
  • Batch testing according to the Certificate of Analysis
  • Batch testing and batch release of clinical and marketing batches
  • Full analysis of all parameters to issue a standalone batch Certificate of Analysis
  • Individual parameter determination to be included in your batch Certificate of Analysis
  • APIs Certificate of Analysis according to relevant pharmacopoeia
  • Requesting Importation Authorization from the Medicines Agency
  • Importation into the EU of drug products (human, veterinary or investigational)
  • Warehousing, sampling, EU depot and shipment
  • Storing retention or reference samples
  • Issuing Qualified Person Declaration (annex 5.22)
  • Auditing manufacturing plant in compliance with EU-GMP
  • Managing quality agreement
  • Reviewing transport conditions
  • Managing out-of-specification, change control and incidents
  • Batch manufacturing record review
  • Batch release in accordance with Marketing Authorization
Laboratory analytist with pipette
Quality Control laboratory

DO YOU NEED MORE INFORMATION OR A QUOTE?

Related Services

Method Development, Validation and Transfer

Development and validation of analytical methods for excipients, APIs, intermediate products and finished products.

Quality Control of Small Molecules

Analytical tests for APIs, excipients, intermediate products, finished products, packaging materials and process environment samples.

Batch Testing and Batch Release

KYMOS and PHARMAPROGRESS are GMP certified and we have a partial manufacturer authorization for Quality Control purposes.

BIOSIMILAR COMPARABILITY STUDIES

Testing lab for biosimilar products – GMP inspected by U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

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