ultraDAWN

Built in the NEON platform, ultraDAWN provides an intelligent user interface indicating real-time and time sequences of molar mass, size and/or particle concentration as well as system health diagnostics and event history. With photodetectors at eighteen scattering angles plus one more to measure light transmitted through the flow cell, the ultraDAWN provides a solution for:

• Macromolecules: M_w from 10³ to 10⁹ g/mol and R_g from 10 to 250 nm
• Nanoparticles: Z-average radius from 10 to 250 nm and corresponding particle concentration (concentration range depends on particle size)

UltraDAWN offers versatile options for PAT, including:

• In-line or on-line configuration
• Process or slipstream flow rates from 0.1 mL/min to 5 mL/min
• Integration with production control software via OPC

In-line - For continuous processes that take place at flows below 5 mL/min, such as microfluidic drug encapsulation or chromatographic purification steps, in-line RT-MALS provides the shortest feedback loop while the ultraDAWN samples the entire process stream.

On-line - When processing takes place within a fixed volume such as a homogenizer, or when the process flow is greater than 5 mL/min, a bypass stream is diverted from the manufacturing process to the ultraDAWN. RT-MALS data are produced in near-real-time.

RT-MALS in Lab R&D

RT-MALS can be implemented early in process development – at pilot plant scales and even smaller, such as regular production of small batches of material for R&D use. Experience with lab-scale RT-MALS paves the way for effective implementation on the production floor.

RT-MALS in Scale-up from Lab to Manufacturing

Scaling up often means re-developing the process, requiring off-line analysis of numerous samples collected from intermediate and final steps. RT-MALS greatly accelerates scale-up: it provides real-time feedback, indicating the effect of method tweaks on CQAs, while simultaneously reducing effort and the number of samples analyzed off-line.

Unlike complex at-line PAT devices, ultraDAWN can simply be left in the process flow upon completion of scale up, for continuous or periodic monitoring of the final process.

RT-MALS on the Manufacturing Floor

ultraDAWN and OBSERVER software are simple, robust technologies that may be employed in different ways during serial production. During initial stages, technicians can visually monitor molar mass and size, intervening in the process as needed. With increasing confidence in the capabilities and reliability of RT-MALS, engineers may implement fully-automated process control using OBSERVER’s configurable triggers. In both cases, all data can be reviewed post-production to determine if any deviations were encountered.

Virus purification

RT-MALS monitors particle radius and triggers when within the specified range, to differentiate from smaller proteins or DNA and larger cell fragments and collect virus-enriched fractions.

TFF concentration

RT-MALS monitors particle concentration in the course of tangential flow filtration. and triggers when above the specified end point, to terminate the process step.

Polysaccharide depolymerization

RT-MALS monitors molecular weight and triggers when below the specified end point, to terminate the homogenization process. See AN8005: RT-MALS end-point determination of a polysaccharide depolymerization process.

Liposome homogenization

RT-MALS monitors radius and triggers if outside the specified range, to divert out-of-spec product from contaminating the collection vessel. See AN8006: In-line monitoring of liposome size by RT-MALS.

OBSERVER

OBSERVER RT-MALS software acquires real-time multi-angle light scattering data from ultraDAWN, then calculates and reports molar mass, radius, and/or particle concentration, thirty times each minute. When the RT-MALS results deviate from specifications or reach the process endpoint, OBSERVER can send a trigger to control the process, via analog voltage or digitally via OPC.

GMP requirements are fulfilled by operating OBSERVER as an OPC client for SIPAT or DeltaV.