Insitec Wet for pharmaceutical processes
PAT solution for real-time particle size analysis of pharmaceuticals.
Engineered to withstand the rigors of the process environment, Insitec Wet for pharmaceutical industry applications provides a robust, proven PAT solution for measuring particles in the size range 0.1 to 2500 µm. Insitec Wet laser diffraction analyzers can be configured to suit practically every wet particulate process, delivering real-time monitoring and control 24/7, with options for:
- Gas or dust zoned hazardous environments
- Fully automated concentration control
An integrated solution that combines a robust laser diffraction particle sizing sensor with fully automated concentration control to deliver continuous on-line (or manual at- or off-line) wet measurement of particulates in continuous or batch processes. This option is used for more concentrated solid-liquid and liquid-liquid streams, with sample dilution closely and automatically controlled via both a pre-diluter and a cascade diluter:
- Uniform, highly polished surfaces to avoid particle build-up; designed for ease of cleaning.
- Base model hardware manufactured to GAMP5 standards and compatible with CIP/SIP requirements to meet specific manufacturing specifications. Options for validation and 21 CFR part 11.
- Easy-to-use software and fully automated operation to minimize training requirements and release operator time.
- Integration with existing control platforms to simplify development of automated control protocols.
- High reliability of > 95% with little downtime, minimal maintenance and maximum ROI.
- Intrinsically safe version available for hazardous zoned environments.
All Insitec installations are tailored to the unique requirements of the application. They range from simple at-line, manually-fed systems to fully automated, validated on-line solutions for continuous monitoring and multivariate control. Malvern works in partnership with its customers, providing expertise, hardware and software, where and when it’s needed. This solutions developed provide information that drives intelligent process development and secures reliable consistent commercial manufacture.
Factors for success
The success of process analysis depends on detailed consideration of three critical components:
- The process interface.
- Sample measurement.
- Data presentation and use.
The process interface
Insitec systems are items of process equipment and operate within the plant environment. Getting the interface between the instrument and the plant right is essential for long-term, trouble-free operation.
Malvern has proven technology for almost every conceivable wet process application. From integrated sample dilution hardware incorporating multistage cascade diluters, for highly concentrated slurries, to simple static samplers for more dilute suspensions and emulsions. Proven strategies ensure that representative samples are automatically and consistently delivered to the measurement zone, in an appropriately dispersed state and at a suitable concentration for analysis.
Insitec at-line systems run alongside the process and have a manual interface. For automated continuous operation the Insitec is installed in the process line or on an associated sampling loop.
Specified with polished connections, and an easy to clean build, all pharmaceutical systems offer excellent performance when applying PAT within the pilot plant environment for design space scoping and DoE or for process monitoring and control at a commercial scale.
Measurement in an appropriately dispersed state ensures access to relevant data whether it is agglomerates or primary particle size that is of interest.
A dedicated Insitec may be necessary for each measurement point or it may be possible to monitor multiple lines or process steps with a single sensor. This depends on the measurement frequency required.
Well-designed on-line process interfaces:
- Deliver sample that is representative of the bulk diluted to an appropriate concentration for measurement.
- Run reliably with minimal maintenance without disrupting the process.
- Recycle analyzed material to minimize waste wherever feasible.
Insitec systems use the technique of laser diffraction to rapidly measure particle size. Complete particle size distributions are measured in less than one second, so even processes with fast dynamics can be tracked effectively.
Insitec systems directly measure the process stream. Many wet processes have high solids loadings making dilution an essential precursor to laser diffraction measurement. However, the patented multiple scattering algorithms associated with all Insitec systems extend the working concentration range of the technique. These algorithms mathematically correct for the concentration-dependent effect of the source light interacting with not one, but several, particles before reaching the detectors. More samples can be measured without dilution; concentrated solutions require less pre-treatment. And all measurements are robustly independent of sample concentration.
Insitec produces reliable, timely and complete data, reporting full particle size distributions. These data provide a secure foundation for better process control whether that control is manual or automated.
Data presentation and use
Insitec systems can be integrated within the process plant. They can be operated as stand alone units or from a centralized control room. Measurement results drive routine decision making during development and in manufacture. Powerful software packages make integration and data interpretation straightforward.
Malvern Link II software provides the functionality required to integrate an Insitec within an existing control system and to automate process control. It allows operation of the analyzer from either a dedicated PC or from existing control mimics. Importantly Malvern Link II is not confined only to Insitec integration. This software also eases integration with other instrument types, simplifying multivariate control.
RTSizer software presents the measurement data in a clear and accessible way. Results reporting can be tailored to industry and customer norms to improve information flow. Insitec data are used to:
- Improve process understanding.
- Accelerate and improve process development.
- Deliver instant upset detection.
- Support comprehensive process optimization.
- Automate process control.
- Improve product consistency.
- Keep records for batch traceability and quality assurance purposes.
Because complete particle size distributions are reported, monitoring and control can be based on whichever size fraction is of interest: the fines, the 3 to 30 micron fraction, the amount of material over 200 microns, for example.
- Measurement type:
- Particle size
- Measurement range:
- 0.1 to 2500µm
- Measurement principle:
- Laser diffraction
- Optical models:
- Mie theory
- ±2% on Dv(50) reported using the verification reticle
- Enclosure rating:
- Operating platforms:
- 10 bar (g)
- RTSizer (for instrument control) Malvern Link II (for system automation and data link)
- Maximum distance from instrument to PC:
- 500m (up to 2 km using fiber optics)
- 10°C – 70°C
- 35% - 80% (non-condensing)