Easily Eliminate High Risk Candidates with AQS3pro
Precisely detect changes in secondary structure, during drug discovery to identify inherently unstable proteins with poor manufacturability
The decision to eliminate or progress potential drug substance candidates relies on gathering relevant and differentiating data from a very small amount of sample. After assessing drug substance activity during drug discovery, testing begins on physical, chemical, biological, and pharmacological properties.
Conformational change in a biotherapeutic protein can be directly associated with poor stability. Structural characterization is therefore a powerful tool for the detection of inherent stability. Indeed, similarity assessments are a valuable way of elucidating binding differences, assessing structural integrity, and identifying a lack of stability, even before aggregates become detectable.
The AQS3pro is a Microfluidic Modulation Spectroscopyanalytical technique for the evaluation of protein secondary structure. In late stage drug discovery and preformulation MMS offers the opportunity to:
- Compare protein secondary structure with high resolution and precision to sensitively detect candidates with poor stability even before aggregates form.
- Efficiently access structural characterization with automated, easy-to-use technology that is well-matched to preformulation workflows.
- Generate data that has value throughout the lifecycle of the drug, with an instrument that can transition through to manufacturing and QC.
The mantra for drug discovery is, of course, fail early, fail cheap. The requirement to fail reliably is less often highlighted, but crucial.
Stability is a critical quality attribute for biological therapeutics and tools for the assessment of protein stability are central to late stage discovery and preformulation. Dynamic Light Scattering, Static Light Scattering, Differential Scanning Fluorimetry and viscometry can all be performed with smaller and smaller sample volumes to assess aggregation in early formulations. However, these tools all detect and quantify aggregates, with varying degrees of sensitivity. They do not characterize the structural changes associated with any lack of stability and aggregation.
Defining features of the AQS3pro for late stage discovery and preformulation
Detect the impact of applied stress earlier. Cut the time taken for stability studies. Improve sensitivity to change. (Concept figurative graphic - stress testing timeline comparison of stability and aggregation. See change in stability way before you’d see aggregation. Don’t have to stress as long, yielding results faster)
The AQS3pro is a Microfluidic Modulation Spectroscopy analytical technique that makes it easier to characterize the secondary structure of proteins. In late stage discovery and preformulation comparative studies of secondary structure can be used to assess inherent stability, in the absence of aggregates. The AQS3pro offers:
- Precision and resolution that surpasses that of alternative techniques such as Circular Dichroism
- Automated, plate-based measurement
- Rapid data processing to generate information that supports effective decision making.
- Transferability, the ability to measure across a wide range of concentrations and in the presence of excipients.
An investment in the AQS3pro can undoubtedly pay dividends in late stage discovery but will still be delivering value as your chosen drug candidate reaches product release since the same measurements performed on the simple solutions associated with preformulation can be duplicated on clinically representative samples. Many analytical techniques suffer from the limitation of being useful at just one stage of the drug lifecycle. Not the AQS3pro. The AQS3pro can travel with a drug candidate through the drug pipeline, directly supporting its transition to commercial success.