Quality Assurance

How AQS3pro Enhances Quality assurance (QA) protocols

Use high sensitivity measurements of secondary structure to elucidate structure-function relationships and detect failure

Effective quality testing provides a foundation for and safeguarding of product quality, controlling critical changes in the structure of drug substances, drug products, raw materials, or excipients. Quality assurance (QA) provides a systematic approach that goes beyond the measure of drug product quality attributes and establishes a set of guidelines for all facets of the manufacturing process that could affect product quality. This includes establishing quality guidelines for raw materials, facility and production line cleanliness, process monitoring, and control all the way to troublshooting product recalls, product returns and non-compliance reporting. 

Biologic drugs are complex molecules that exhibit microheterogeneity, minor chemical variances such as glycan structural differences, deamidation, oxidation and glycation. Casting a wide analytical net helps establish the robust structure-function relationships that define the boundaries of unacceptable risk. The identification of all possible critical quality attributes (CQAs) underpin effective QA.

RSB backgrounds

The AQS3pro facilitates the measurement of secondary structure attributes of biopharmaceuticals in all stages of the manufacturing process. This helps establish quality parameters at stages not possible with traditional techniques. AQS3pro data can be used to establish quality measures relating to protein concentration, purity, stability, aggregate detection, and prevention. Implementation of the technique as a comparability tool also provides measures of lot-to-lot comparison, identifying potential deviations in manufacturing through the establishment of libraries of fingerprint spectra at all stages of production. The instrument offers:

  • Highly repeatable and reproducible measurement of testing protocols.
  • Ability to detect differences in secondary structure that cannot be robustly determined with traditional techniques.
  • A 21 CFR part 11 compliant automated platform that supports the efficient integration of structural measurements in existing QA workflows.
  • Powerful and intuitive software that accelerates data analysis enabling highly informative insights by even a novice analyst.

The result is a valuable analytical tool for assessing the consistency of materials and processes, from early stage development through the final product. Comparability and similarity testing with the AQS3pro is simple, fast and highly differentiating.

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Comparability: Is this protein the same as the one that was manufactured last week?

Demonstrating the consistency of a biologic therapeutic is a substantial challenge. As ICH Q11 makes clear, biotherapeutics may ‘possess such a large number of quality attributes that it might not be possible to fully evaluate the impact on safety and efficacy of each one’. The difficulty of identifying Critical Quality Attributes (CQAs) is widely recognized and calls for a pragmatic approach involving knowledge gained from early development that is iteratively updated with data from non-clinical and clinical studies.

The sensitive detection of any relevant deviation from an established structure or formulation composition can be valuable and informative. Quality attributes are identified through rigorous risk assessment and as understanding increases on the impact of parameter changes have on biological characterization. This is a common strategy for ensuring robust QA and pinpointing the CQAs that will, ultimately, form the specification for product release.

Why use secondary structure as a metric in QA?
Transforming the practicalities of measurement: How is secondary structure measurement by CD or FTIR different?

Benchmarking AQS3pro: Sensitivity with Spiked IgG

The performance of the AQS3pro in quantifying, comparing and contrasting critical attributes of a biologic formulation sets it apart from other technologies. Elion Labs collected data that represents a model experiment to determine a theoretical limit of detection (LoD). In this experiment a 20mg/mL IgG formulation was measured. To determine the LOD of contaminants, BSA was added representing  1-10% of protein content. The plots below show the spectra obtained from FTIR, MMS, and CD respectively. Spectral processing determined the composition of alpha-helix using Microfluidic Modulation Spectroscopy at a theoretical LOD around 0.76%, in contrast to 22.7% and 3.7% found using FTIR and CD respectively.

Take another Look at what the AQS3pro has to offer 

AQS3pro is a versatile analytical instrument that makes secondary structure measurements applicable and accessible for QA. It enables precise comparability studies, detecting structural changes with high sensitivity. The AQS3pro offers:

  • The ability to differentiate samples with greater precision and sensitivity than can be achieved with incumbent technology for secondary structure measurement
  • Automated, plate-based measurement for high throughput testing
  • Data processing software that takes all users directly to informative unambiguous results
  • Broad applicability, sample measurement from discovery through to fill and finish/product release with minimal sample preparation
  • The complementary detection of changes in excipients and composition.

The AQS3pro transforms the feasibility of using secondary structure as a discerning metric in QA, enabling full exploitation of the detailed insight it can provide. From development to product release it provides metrics that can be used to streamline and enhance the QA protocols used to robustly identify sub-standard raw materials and detect process failure. Simple to use, sensitive and unambiguous, AQS3pro data augments your ability to detect difference and safeguard product quality.