Label-Free Assays for Quality Assurance (QA) and Quality Control (QC)
Label-free detection has become an integral part of the quality assurance (QA) and quality control (QC) departments in the pharmaceutical and biotechnology industries. It empowers QA and QC teams to uphold the highest standards by offering a more efficient, accurate, and cost-effective solution for ensuring product quality.
The Octet® BLI platform enables the analysis of a wide range of samples, from purified proteins to complex mixtures. This flexibility supports the comprehensive evaluation of raw materials, intermediates, and final products, providing a holistic view of the production process. Moreover, it allows for the continuous monitoring of critical quality attributes (CQAs) throughout the production process, ensuring that each batch meets stringent regulatory standards. The precision and reliability of label-free detection are invaluable, enabling the rapid assessment of product consistency and potency.
By eliminating the need for labels, it reduces the complexity and cost of assays while also minimizing potential interference with the biological activity of the studied molecules.
QA/QC release testing are critical components in the production of biological drug products, ensuring that each product meets rigorous safety and efficacy standards. These products must undergo QC testing using robust, qualified, and validated methods under Good Manufacturing Practice (GMP) conditions. The Octet® BLI platform is designed to streamline this process, facilitating method development for in-process and lot release testing that can be seamlessly transferred to QC environments.
With its user-friendly interface and high throughput capacity, the Octet® system significantly enhances productivity, offering up to 40 times the efficiency of traditional enzyme-linked immunosorbent assays (ELISA). The platform is equipped for GMP implementation, featuring Octet® CFR software and server applications for secure and traceable electronic record keeping. Additionally, optional IQ/OQ/PQ packages are available to ensure that instruments are installed, operating, and performing as intended. Comprehensive support services and biosensor validation further complement the comprehensive GxP package for QA and QC release testing in the biopharmaceutical industry.
QA/QC Release Testing: Benefits and Challenges
Advantages
Ensures Product Safety: QA/QC release testing ensures that drug products meet safety standards, protecting patients from potential harm due to contaminants or impurities.
Regulatory Compliance: It ensures that products comply with regulatory requirements, facilitating approval processes and market entry.
Consistency and Reliability: QA/QC testing ensures consistency and reliability in drug products, maintaining the integrity of the brand and trust with healthcare providers and patients.
Early Detection of Issues: By identifying potential issues early in the production process, QA/QC testing helps prevent costly recalls and production delays.
Challenges
Inflexibility: Due to their established nature, QA/QC departments may be inflexible in adopting new assays or modifying existing ones, potentially hindering innovation and adaptation to new technologies.
Time-Intensive Validation: The validation process for new assays is time-intensive, requiring extensive testing and documentation to ensure they meet the necessary standards for accuracy and reliability.
Resource Constraints: Implementing and maintaining these assays can be resource-intensive, requiring specialized equipment, trained personnel, and ongoing quality control measures.
Adaptation to New Regulations: As regulatory standards evolve, existing assays may need to be re-evaluated and adapted, which can be challenging for QA/QC departments that rely on established methods.
Featured Applications
Impurity Testing
Quickly detect and monitor potential process induced impurities such as host cell proteins (HCPs) and protein A residues with better precision and robustness than traditional ELISAs.
Sartorius provides ready to use Octet® kits for the detection of residual protein A and CHO based HCPs.
The Residual Protein A kit is designed to detect recombinant protein A constructs and MabSelect SuRe™ (Cytiva) down to 100 pg/ml.
The Anti-CHO HCP detection kit using Anti-CHO antibodies (Cygnus Technologies) can detect as low as 0.5 ng/ml of HCPs with precision of 5 - 10% CVs.
Enhanced Productivity and Labor Efficiency in Lot Release and In-Process Testing of Biologics
Octet® BLI instruments can be equipped with 21 CFR Part 11 Software for compliance with regulatory requirements. Compliance is further enhanced with the availability of instrument qualification kits including IQ|OQ and PQ kits that ensure the platform performs as stipulated. This white paper includes a few examples to demonstrate the suitability of BLI technology under GxP compliance for different applications and shows the relative benefits over alternate technologies.
Modernize Biopharmaceutical QC Testing to Increase Efficiency
Up to 2x faster and with the ability to process 40x more samples per day, Octet® BLI systems are an ideal replacement for ELISA, HPLC or other label-free techniques for the quantification of antibodies and recombinant proteins and is especially suitable for product potency lot release assays. Boehringer Ingelheim were able to develop an active Fab quantitation assay for in-process testing as well as stability and lot release testing in less than one week using the Octet® BLI platform.
Examples of Approved Drugs Utilizing Octet® BLI Data in Their Applications
This table includes examples of drugs where the Octet® BLI system has been used to generate data submitted as part of the supporting information for the drug’s approval with regulatory bodies.
Drug Name | Target | Drug Modality | Sponsor | Regulatory Agency | Indications | Application | Year of |
|---|---|---|---|---|---|---|---|
Keytruda | Pembrolizumab | PD-1 | mAb | Merck | EMA | Non-small cell lung cancer | Affinity Characterization | 2015 |
Tecentriq | Atezolizumab | PD-L1 | mAb | Roche | EMA | Non-small cell lung cancer | Specificity | 2017 |
Comirnaty | BNT162b2 | COVID-19 | mRNA Vaccine | Pfizer | EMA | COVID-19 | Affinity Characterization | 2020 |
Ultomiris | Ravulizumab | Human C5 | mAb | Alexion | EMA | Paroxysmal nocturnal hemoglobinuria (PNH) | Affinity Characterization | 2019 |
Livogiva | Teriparatide | PTH | Peptide Biosimilar | Teva | EMA | Osteoporosis | Affinity Characterization | 2020 |
Atoltivimab, maftivimab, and odesivimab-ebgn | EBOV glycoprotein | mAb Cocktail | Regeneron | FDA | Ebola virus | Competition studies | 2020 |
Oyavas | Bevacizumab | VEGF-A | mAb Biosimilar | Mabxience | EMA | Non-small cell lung cancer | Specificity | Affinity Characterization | 2021 |
Jemperli | Dostarlimab | PD-1 | mAb | GSK | EMA | Endometrial cancer | Affinity Characterization | 2021 |
Regdanvimab | S protein | mAb | Celltrion | EMA | COVID-19 | Affinity Characterization| Blocking Assay | 2021 |
Xevudy | Sotrovimab | S protein | mAb | GSK | Vir Biotechnology | EMA | COVID-19 | Affinity Characterization | 2021 |
Nuvaxovid | COVID-19 | Vaccine | Novavax | EMA | COVID-19 | Affinity Characterization | 2022 |
Kimmtrak | Tebentafusp | CD3 | gp100 | TCR | Immunocore | EMA | Uveal melanoma (UM) | Specificity | 2022 |
Tixagevimab | Cilgavimab | COVID-19 | mAb Combination | AstraZeneca | FDA | COVID-19 | Affinity Characterization| Blocking Assay | 2022 |
Opdualag (nivolumab | relatlimab) | LAG-3 | PD1 | mAb Combination | BMS | EMA | Melanoma | Blocking Assay | 2022 |
Briumvi | ublituximab | CD20 | mAb | Propharma Group | EMA | Relapsed Multiple sclerosis | Specificity | Bridging | 2023 |
Elrexfio | elranatamab | BCMA | CD3 | bsAb | Pfizer | FDA | Relapsed Multiple myeloma | Specificity | Bridging | 2023 |
Leqembi | lecanemab | Aβ aggregates | mAb | Eisai | FDA EMA | Alzheimer's Disease | Specificity | 2023 2024 |
Ahzantive | aflibercept | VEGF-A | PlGF | Recombinant fusion protein biosimilar | Klinge Biopharma | EMA | Retinal disorders | Specificity | Blocking Assay | 2024 |
Baiama | | VEGF-A | PlGF | Recombinant fusion protein biosimilar | Formycon AG | EMA | Retinal disorders | Specificity | Blocking Assay | 2024 |
Epruvy | ranibizumab | VEGF-A | mAb fragment biosimilar | MIDAS Pharma | EMA | Retinal disorders | Specificity | Blocking Assay | 2024 |
Tuznue | trastuzumab | HER2 | mAb biosimilar | Prestige Biopharma | EMA | Breast and gastric cancer | Specificity | Blocking Assay | Bridging | 2024 |
Featured Resources
Instant Access
Assuring Accuracy, Preventing Fraud - The Critical Role of Validation in Bioanalytical Methods
PDF | 897.8 KB
Instrument Comparability Assessment: Kinetics Precision Assessment in Ligand Binding Assays on the GxP-Compliant Octet® RED96e and Octet® R8 Instruments
PDF | 1.3 MB
Enhanced Productivity and Labor Efficiency in Lot Release and In-Process Testing of Biologics in GxP Laboratories
PDF | 924.3 KB
