In general, particle size analyzer prices can range from $35,000 to $250,000. The more an analyzer can do, the higher its price. It is also important to determine other factors that will add value to the right particle analyzer, including technology that allows tests using small samples, and that allows for particle testing earlier on in the discovery and development process.
The role of particle size analyzers
Therapeutic proteins have proven to be effective treatments for human diseases. But immunogenicity can compromise the efficacy of these new therapies, and lead to patient suffering and even death.
Much of that immunogenicity comes from protein aggregates and particles, partially unfolded molecules that “come for the ride” as part of the therapeutic protein’s ensemble of molecules. In addition, exposure to air, solids, light, or changing temperatures (often parts of the pharmaceutical development process) can produce protein particles.
It is essential, then, for pharmaceutical manufacturers to correctly identify and quantify these particles and remove as much of them as possible. Halo Labs and other manufacturers have developed particle analysis equipment (including the Aura® family of analyzers) that uses a number of techniques to characterize and measure the number and size of these particles. These instruments also help fulfill USP788 measurement requirements, as well as FDA regulations that demand that such particles be virtually eliminated from the final therapeutic product.
Particles have been observed in three size ranges:
- Stable particles in solution (nanometer-sized)
- Subvisible particles (between 1 and 100 micrometers)
- Visible particles (greater than 100 µm)
Subvisible particles pose the greatest risk to patient safety and can provide early warning signs of product stability problems. Additionally, of the 3 ranges described, subvisible particles are also the most difficult to characterize when considered for patient safety.
Identify, count and size for cells, proteins and plastic contaminants
The cost of particle size analysis
Prices of particle size analyzers can vary a great deal. Much of the cost is based on what technology the analyzer is based on, its range of capabilities, and the sample size required. Halo Labs, for example, offers four Aura particle analyzers, each with differing capabilities and applications. All Aura systems detect, size, count, identify, and analyze particles, and can identify proteins. But Aura systems can vary by application:
- Aura+; interdisciplinary biotherapeutics all-in-one system
- Aura CL; for cell therapy, can identify cell aggregates and conduct cellular assays (e.g., cell viability), and contaminants, particulates, and impurities
- Aura GT; for gene therapy, can identify capsid and viral vector aggregates, detect nucleic acid leakage (e.g., DNA) and proteins
- Aura PTx; for immune/biologics (antibody and proteins) therapy, identifies polysorbate and proteins, and conducts immunoassays
As previously mentioned, the more an analyzer can do, the higher its price will be in general. It is also important to determine other factors that will add value to the right particle analyzer, including technology that allows tests using small samples, and that allows for particle testing earlier on in the discovery and development process.
Particle Size Analyzers, Particle Counters, and General Particle Analyzers—what’s the difference?
ID, count and size multiple particle types
Size analyzers, counters, and general analyzers all provide some degree of insight into particles in your sample. However, each produces different results and varies in its degree of characterization. Choosing the right analyzer will depend on the data you need.
Particle counters—these instruments simply quantify the number of particles in a sample, and provide a concentration in the sample. Types of counters include light microscopes or portable and even hand-held instruments. These counters can detect particles in liquid and air and on surfaces. However, traditional particle counters do not provide images of the actual particles themselves.
General particle analyzers—these instruments can provide basic information on particle number, size, and shape, but generally cannot look at subvisible or smaller particles.
Particle size analyzers—like the Aura family of instruments, these provide several characteristics of particles, including count/concentrations, identification, but also size, shape, and other attributes. These are the most effective at determining the presence and size of subvisible particles, which present the greatest risk of reducing therapeutic stability.
Particle size analyzer variability
Depending on the technology used and the sensitivity required, there is probably a size analyzer to meet your needs. Each analyzer is tailored to specific particle sizes and types:
Dynamic Light Scattering—used to measure particles from 0.3 nm to 10 µm. These instruments work using Brownian motion, in which lighter particles move faster than heavier (and therefore larger) ones. A laser illuminates the particles and the scattered light is analyzed. Fluctuations in intensity determine size distribution in a sample.
Laser Diffraction—leverage diffraction patterns produced by a laser beam when it passes through an object, ranging in size from nanometers to millimeters. The technique quickly measures a particle’s geometric dimensions (from 10 nm to 2,000 µm).
Size and Exclusion Chromatography—Evaluates the size distribution of molecules, from 4 to 12 µm. These analyzers separate molecules according to size, using a column packed with tiny porous beads.
Light Obscuration—quantify particles greater than 10 µm, and measure down to 2 µm. The analyzers pass a sample through a narrow opening in the device, measuring light obstruction caused by individual particles to determine size and concentration.
Flow Imaging—captures particle images in a flow cell to calculate the size, shape, count, and other attributes. These cover a size range from 1 to 400 µm.
Light Microscopy—a traditional technique that counts and characterizes subvisible particles in the size range of 0.8 to 150 µm
None of these techniques, however, can detect invisible particles and provide adequate protection against the contamination of therapeutic samples. Larger sample sizes, inadequate detection capabilities and the need for multiple instruments and testing runs all increase the price of particle detection (and in turn, therapeutic development).
Why Choose Halo Labs Particle Analyzers?
Subvisible protein particles can negatively impact clinical performance to a greater degree than other degradation-related products, such as soluble aggregates and chemically modified species of protein. The Aura family of particle analyzers uses Backgrounded Membrane Imaging (BMI) and Fluorescence Membrane Microscopy (FMM) to uncover this important subvisible particle data. This data analysis step is also possible at the very beginning of your process, speeding up development and letting you make better decisions, increasing the probability of being first to market. Aura can:
- Detect, identify, and characterize particles not measured by dynamic light scattering or size exclusion chromatography
- Preserve samples, using as little as 5 µl per test
- Move quickly with an analysis time of 1 minute per sample
- Get detailed information on size, morphology, count, and distribution (not possible using other methods)
- Fluidics-free completely eliminating apparatus errors and malfunctions
- Fluidics-free completely eliminating apparatus errors and malfunctions
Particle Size Analyzer Price Case Study: Example of Equipment of Investment and ROI
A particle size analyzer made by Company X (a competitor of Aura) was recently tested for its ability to evaluate the stability of adeno-associated virus (AAV) gene therapy products. Based on flow imaging, the instrument evaluated subvisible particles (between 1-100 µm) at 37°C and 75°C.
The instrument tested was able to show an increase in particle count at 37°C, and an overall decrease in particle counts at 75°C, possibly due to denaturation of AAV at that high temperature.
While the tests showed the capability of detecting subvisible particles, the sample sizes used were quite high (0.9 ml and 0.61 ml). This is orders of magnitude higher than samples used by the Aura family of particle size analyzers (5 µl per test). By using less sample, the Aura analyzer can more efficiently provide key subvisible particle data, in less time, increasing the value of investment in potential therapeutic proteins.
Conclusion and Key Takeaways
Detecting subvisible particles is a crucial part of preserving the structural and functional integrity of therapeutic proteins. In addition, their removal is a requirement under USP 788 and US FDA regulations. The Aura family of particle size analyzers stands ahead of other methods, due to:
- More thorough detection capabilities due to Backgrounded Membrane Imaging (BMI) and Fluorescence Membrane Microscopy (FMI)
- Detection made earlier in the discovery and development process, making key decisions easier and more efficient, and bringing products to market faster
- Use of much smaller sample sizes (5 µl per test) compared to other methods, and faster test times (1 minute)
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