Eliminate High Risk Drug Candidates Easily with AQS3pro

Precisely detect changes in secondary structure 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, 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.

Discovery image

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.

Find out how the AQS3pro boosts your team's efficiency

Pharmaceutical Preformulation: How early can you reliably fail?

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.

Why wait till aggregates form when secondary structure predicts stability earlier?
Narrowing the pipeline, earlier

Defining features of the AQS3pro for late stage discovery and preformulation

Automated, non-expert operation

Microtiter, plate based (96 well plate compatible), automated measurement and data processing that rapidly take even inexperienced users from analysis to usable information.

Clarity and precision

The ability to detect differences in secondary structure with a precision and resolution that is inaccessible with current techniques, and that enables the unambiguous determination of aggregation mechanisms. 

Concentration Range

While the AQS3pro can be used with samples as dilute as 0.1 mg/mL it can also measure high concentration, clinically representative formulations without sample preparation. Using the AQS3pro in discovery therefore helps to establish a stability profile that can transfer with a drug candidate through to commercialization.

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)

Secondary structure versus aggregation

AQS³pro Benefits

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.