PAT Movement Bringing Laboratory Analysis Online
Among the U.S. Food and Drug Administration's latest admonishments to the pharmaceutical manufacturing community is for the increased use of process analytical technology (PAT).
Broadly defined, PAT encompasses a variety of tools, technologies and methodologies designed to shift the industry's quality focus from post-production inspection to building quality into its products and into the manufacturing process. Indeed, FDA's expansive definition of analytical in PAT includes "chemical, physical, microbiological, mathematical, and risk analysis conducted in an integrated manner."
A major component of the initiative's intent, however, has been more narrowly focused on the movement of traditionally laboratory-based determinations of product chemical composition or physical properties such as particle size distribution, to instruments on the production floor.
Commonly referred to as process analyzers or process analytical chemistry tools, these devices help improve production efficiency and quality by eliminating the time delays inherent in taking and transporting a sample to an off-line laboratory. Many operate inline and in real-time "improving response times to process upsets and often eliminating the need for sampling altogether.
Here, then, a sampling of recent PAT tools for the pharmaceutical manufacturing marketplace.
Crystal Size and Shape in Real Time
Crystal Scope is an online PAT tool designed to help optimize processes by providing crystal particle size and shape in real time. The Canty variable length insertion probe with patented camera light combination continuously sends live images to the image processor. The image is then analyzed to provide two dimensional size data from the point of nucleation (1micron or greater) through to full crystalline structure. The system is CFR Part 11 compliant and has the advantage of providing visual verification. Size, shape and particle density data is provided to control systems via Ethernet, Excel or 4-20mA.
Online Laser Diffraction Enables Statistical Particle Size Analysis
Ensemble laser diffraction provides a highly repeatable, accurate and simple analysis long proven in laboratory installations. Because each measurement includes thousands, or even millions, of particles, this approach is much more statistically significant than particle counting systems, according to the manufacturer. Malvern Insitec systems provides on-line particle sizing from 0.5 to 1000 micron with continuous measurements every 0.25 seconds. Correct dispersion of particulates prior to measurement is achieved using the company's Jet-stream (dry) and Gulf-stream (liquid) eductor systems. Insitec T model is designed for GAMP4-compliant processes complete with hygienic fittings for easy cleaning. Insitec X features intrinsic safety as well as GAMP4 compliance and is intended for use where vapors or dust may constitute explosion hazards. Patented dilution systems coupled to the Insitec L model now allows particle sizing even in concentrated slurry streams.
Malvern Process Systems
Fiber Optic Probes for NIR Analysis
Three new models of near infrared Vector probes are designed for diffuse reflectance spectroscopy applications requiring high sensitivity and dynamic range. The new models include the NIR-H, a 10-cm probe with a gun-handle grip for ease of handling. The NIR-HT also provides a built-in trigger, LEDs and a serial port interface to allow convenient connection to computer systems. The NIR-MB is available with probe head lengths up to 30 cm and a versatile "torpedo-shaped" barrel grip. The NIR-MB is also supplied complete with mounting accessories for fixed-position operation. A proprietary optic design allows for exceptionally low internal light reflection and high light collection efficiency ensuring high signal to noise characteristics.
Lambda Solutions, Inc.
Flow Cytometer Automates Particle, Cell Analysis
FlowCAM (Flow Cytometer and Microscope) automates the counting, imaging, and analysis of particles or cells in discrete samples or in a continuous flow. It has the ability to process samples at flow rates up to 10 milliliters per minute "up to 200 times faster than current flow cytometers, according to the manufacturer.
For immediate review of test results, the FlowCAM offers users an interactive software interface, which is presented immediately after termination of a run showing the distribution of each cell or particle's size. The distribution is depicted in a Scattergram (photo) where each dot corresponds to an actual measured cell. The user can select a region of interest on the plot and view images of particles specific to the group of dots chosen. This proprietary tool enables exact identification of particles of a specific size or shape on a real-time basis.
Fluid Imaging Technologies
Software Automates Sensor Validation and Fault Analysis
Falconeer III software package uses a novel methodology for performing automated process sensor validation and predictive fault analysis in combination with predictive statistical process control methods. Based on heuristics of normal process operation, the software engine automatically creates and maintains all of the diagnostic patterns and rules necessary to perform its analysis on-line and in real time, according to the manufacturer. The system identifies when the process is running optimally and under control, reducing costs associated with process inefficiencies, downtime, and product reject. Real-time operator alerts help in the early identification of sub-optimal conditions and their prompt correction.
Integrated Liquid Analyzer Eliminates Need for Transmitter
DirectLine series of dissolved oxygen, pH and conductivity probes combines recent advances in microelectronics technology with the proven performance of the company's analytical sensors. The integrated module eliminates the additional time and cost of installing an analyzer or transmitter, separate preamp and special cable, thus providing savings and ease of use during installation, start-up, operation, and maintenance. With all DirectLine modules, the output of the sensor connects directly to any host monitor or control device that accepts standard 4-20 mA inputs and provides external loop power.
Easy-to-Use Density Meter Logs Multiple Parameters
Densito 30PX density meter is designed to provide users with quick and accurate results more efficiently, while storing more than 1,000 sample results including sample ID, measurement unit, temperature compensation coefficient and the date/time. The unit incorporates an easy-to-read pictogram-labeled key design and a backlit dot-matrix display, showing results with date/time stamp in large digits. The user simply immersing the sampling tube, pulls the trigger and reads the meter's result.