A microscope is needed in order to perform the Microscopic Particle Count Test, and it must meet specific requirements. The microscope must have an ocular micrometer that must be calibrated with and objective micrometer. The microscope must have a mechanical stage capable of holding and traversing the whole of the filtration area of the membrane filter. The microscope must have two suitable illuminators, so that episcopic illumination is provided in addition to oblique illumination. The microscope must be adjustable to 100 ± 10 magnifications.

The restrictions for the tests are such that only a relative error within ± 2% is acceptable for the linear scale of the graticule.

The results for the Method 1 test comply with the standards if the sample tested does not exceed 6000 particles, on average, per container that are equal to or greater than 10 micrometers, and must not exceed 600 particles equal to or greater than 25 micrometers per container. The results for the Method 2 test comply with the standards if the sample tested does not exceed 3000 per container equal to or greater than 10 micrometers, and does not exceed 300 particles equal to or greater than 25 micrometers per container.

Since such specific limits are set for the allowable undissolved particles, a precise, powerful tool is needed to comply with these standards. The ASPEX Rx is the ideal tool for these tests, being able to quickly and accurately identify foreign particles as small as 0.1 microns. The Rx also is set to perform one click reporting for fast results.  Since Rx is designed specifically for the pharmaceutical industry, it is the clear choice for analysis of metallic particles and the identification of particulates within both drug powders and suspensions.

The Aspex Personal Scanning Electron Microscope (Personal SEM(R)) with the Rx integrated software is the ultimate automated choice for meeting the USP standards set forth in Test Section 788 with ease and accuracy, built for the pharmaceutical industry with that industry in mind.

Reference:

U.S. Pharmacopoeia, http://www.usp.org/pdf/EN/USPNF/revisionGeneralChapter788.pdf

Aspex, http://www.aspexcorp.com/products/rx.html

Aspex, http://www.aspexcorp.com/industries/health-sciences-reported-info.html

Information about particle type, size distribution, morphology and chemistry is used to identify potential contaminates, as well as minimize the cause of contamination. This information can then be used to develop controls for production in FDA-regulated environments.  More manufacturers are now opting for the Quality by Design (QbD) approach to assess the safety of drug products by understanding the entire process and making changes to the process before the final product is completed.   When following this approach it becomes necessary to find a monitoring technique that fits the needs of the testing facility and allow changes to the process immediately.

There are various techniques available to count and size particles, each with advantages and disadvantages. ASPEX’s Personal SEM® (PSEM) in conjunction with the Automated Feature Analysis (AFA) software is a solution that counts and sizes particles but also gives the chemistry of the particles.  This automated particle analysis tool can then be used to locate the source of the contamination during the process.  With the easy and quick reporting changes to the process can be made quickly to save downtime and maximize profit.  ASPEX’s PSEM complies with 21 CFR part 11 demands and adheres to requirements of cGMP facilities.

Secondary electron imaging is used to obtain surface information to qualitatively describe the sample using surface defects, porosity and tri-dimensional structure evaluation. Backscatter electron imaging displays compositional contrasts used to find features during the automated analysis, and can be digitally stored or captured on film. The energy dispersive spectrometer (EDS) uses silicon drift detectors (SDD) to provide high throughput particle analysis but providing the chemical composition and relative proportions of the sample.

Particle Size Distribution is a valuable tool for pharmaceutical production, leading to identification and possible elimination of harmful foreign particulates. By utilizing the Personal Scanning Electron Microscope (PSEM) with Automated Feature Analysis (AFA) software, pharmaceutical companies have the most powerful tool on the market to quickly and accurately analyze particles.

Reference:
Foreign Particle Size Distribution and Characterization in Pharmaceutical Products Using a High Throughput Electron Beam Analyzer

http://www.pharmpro.com/ShowPR.aspx?PUBCODE=021&ACCT=0015199&ISSUE=0811&RELTYPE=ATO&PRODCODE=6040&PRODLETT=A&CommonCount=0

In order for the developers to produce this desired state of product, they need to have a complete understanding of all the pieces involved in the process, both of the raw materials and the intermediates as well as the interactions between the two. In other words, they must understand how the Critical Process Parameters (CPP) affects the variability in the Critical Quality Attributes (CQA) so that these can be measured and controlled in the manufacturing process. The solution needed to identify and analyze products in real-time is the ASPEX® Rx for the Personal Scanning Electron Microscope (PSEM).

ASPEX® Rx allows manufacturers a way to identify and analyze foreign particles in the production process by using the automated analysis to acquire images, morphology and elemental composition information with a dedicated interface. By allowing for quality control through the product stream, manufacturers can quickly identify foreign particles that would otherwise compromise their product’s quality. And since ASPEX® Rx can identify particles as small as 0.1 microns, it is an ideal tool for microcontamination quality control.

The benefits of the FDA’s QbD to the business are plentiful. Since these products by their very design are superior quality, there is a reduced failure rate in the product batches. Also, since there is less need for final product testing, which can end up costing the manufacturer and the consumer money, the cost of operations and the cost of the product could be lowered. Since there is also increased predictability of product quality in the manufacturing process, there can also be faster approval for new products.

The advantages to QbD in the pharmaceutical field, while changing the way manufacturers think about product production, can greatly outweigh any upfront costs that are needed to see the system put in place. ASPEX® Rx for the PSEM is an affordable micro contamination analysis solution for manufacturers to comply with the FDA’s QbD standards.

References:

Aspex Rx, http://www.aspexcorp.com/products/rx.html

NGP(http://www.ngpharma.com)

Pharmaceutical Processing (http://www.pharmpro.com)

The amount of energy released is based upon the starting and ending shell of the electron. The resulting x-ray can be converted into an EDX spectrum plot. This plot shows the different peaks that correspond to the energy levels of the x-rays received. Each part of the sample can be identified by comparing the x-ray against other known atomic structures, since each element has a unique structure. These plots can be shown as a elemental map to evaluate several elements at once or as a line profile to identify a single element.

There are two major types of detectors used for EDX, Lithium drifted Silicon Detector (SiLi) or the Silicon Drift Detector (SDD). While the SiLi must be operated at liquid nitrogen temperatures, the SDD is capable of being used at relatively high temperatures. The SDD has several other advantages over the SiLi, including faster analytical capabilities and better resolution, as well as higher count rate. The larger count rates also have the added benefit of reducing the damage to the sample because smaller specimen currents can be used.

While there are some free-standing EDX machines, SEMs are the typical equipment of choice. Since SEMs have the added bonus of imaging, they can become an integrated SEM-EDX instrument. Aspex’s Personal Scanning Electron Microscope (PSEM(R)) comes standard with an EDX spectrometer and utilizes a SDD X-Ray. Capable of EDX resolution of 135 eV and a particle detection range of 100nm to 5mm, the PSEM is a reliable, easy to use instrument.

Typical uses for EDX include foreign particle analysis, corrosive evaluation, coating composition analysis, and small component material analysis. Industries such as defense, automotive, pharmaceutical and aerospace (Should we link to these industry pages) are common places EDX analysis is used. The PSEM Express is a benchtop SEM that, when combined with Aspex software such as Automated Feature Analysis (AFA) and Complex Feature Analysis (CFA), becomes a fast, fully automated, affordable desktop SEM analysis system.

Reference:

Aspex, http://www.aspexcorp.com/products/psem-express.html

EDX Analysis and WDX Analysis, http://www.siliconfareast.com/edxwdx.htm

Materials Evaluation and Engineering, Inc., http://mee-inc.com/eds.html

Wikipedia, http://en.wikipedia.org/wiki/Energy-dispersive_X-ray_spectroscopy

From paint to oil, engines to steel content, being able to quickly and accurately analyze particle contamination that could affect the quality of the final product is a necessary step. Since contaminates in steel can alter the grain size, and debris in oils and fluids can effect product life, it is advantageous to take precautionary measures to ensure not only that the end product is up to code, but in order to prevent wasted materials that do not meet the company standards. One tool used to help identify and categorize these particles is a scanning electron microscope (SEM) with energy-dispersive X-ray (EDX) capabilities.

The Aspex Personal Scanning Electron Microscope (PSEM) comes standard with an EDX spectrometer and utilizes a silicon drift detector (SDD). EDX technology is used in various industries, such as the automotive and pharmaceutical industries, for foreign particle analysis, corrosive evaluation, and compositional analysis. With EDX resolution of 135 eV and a particle detection range of 100nm to 5mm, small particles are easily identified and sized.

Aspex also has several different software platforms to fit all your analytical needs. The Advanced Quality Control (AQC) software, part of the Perception Suite, provides manufacturers with the capability of evaluating the size, shape, and composition of all particles present in a sample. By inserting the PSEM with AQC into the product line, problem spots can be isolated and controlled, pinpointing where particles are entering the line well before the end product testing is started, thus saving the manufacturer from wasting time creating faulty products.

Whether in the lab or in the shop, the PSEM with EDX capabilities and the AQC software provides the manufacturer with reliable particle analysis techniques to help ensure that the quality of the design is maintained in each step of the manufacturing process.

Reference:
Aspex, http://www.aspexcorp.com/industries/industrial-automation.html

The level of cleanliness a system needs depends on the system itself; contaminates to the system reduce the life of the parts by accelerating wear, causing reduced efficiency, increased down time, and increased cost due to replacing parts. Both particle wear, caused by metal pieces rubbing against each other, and water wear can effect the system, breaking down essential pieces needed to function and ultimately leading to mechanical failure. Therefore, it is crucial that manufacturers and machinists monitor the cleanliness of these systems.

In order to efficiently monitor the hydraulic or lubrication systems for particle contamination, manufacturers have turned to SEM microscopes, such as the Aspex Personal Scanning Electron Microscope (PSEM). The PSEM uses its Advanced Quality Control (AQC) software to identify and size particles within the system, and can be used directly on the shop floor. Once the particles are identified, the AQC can also show the elemental composition of the particles so that manufacturers and machinists can find the root of the problem upstream and take corrective action.

The AQC can easily identify and categorize particles far smaller than current optical and gravimetric inspection techniques. Also, it has been found that eliminating the particles from a system is much less cost-effective than eliminating the source of the contamination. By implementing the PSEM with AQC, manufacturers and machinists have a tool capable of reducing their manufacturing and warranty failures by upwards of 30% – vastly outweighing the cost of implementation.

The PSEM with AQC by Aspex is revolutionizing the way manufacturers create, implement, and maintain critical cleanliness, in the lab or in the shop. Aspex’s Industrialized-By-Design™ product line offers robust particle analysis solutions for manufacturers in need of easy-to-use equipment for contamination monitoring down to the single particle level, allowing them to control the cleanliness of their hydraulic and lubrication systems from the shop floor.

Reference:

Aspex, http://www.aspexcorp.com/industries/industrial-automation.html
MachineryLubrication, http://www.machinerylubrication.com/article_detail.asp?articleid=800

In order to help clarify the different types of particle information available, the American Society for Testing and Materials (ASTM) has implemented standards for particle characterization, ASTM E1617. ASTM breaks down this information into three levels. The first level gives very basic information about the material. The second level provides more of the methodology applied to produce the first level of information. The third level provides enough details that the procedure can be reproduced. Even though this information may seem to leave little room for error, the way in which the particles are measured, such as differences in handling, acquisition, preparation, and particles size measurement ranges, can have a vast impact on the resulting ASTM level.

Particle characterization requires the analyzer to be very specific, being able to size and shape particles in the sub-micron range. It is more practical to use an automated electron-beam instrument than optical, laser diffraction, or gravimetric instruments, due to electron-beam analyzers having superior magnification ranges, greater depth of field, and more powerful contrast mechanisms. When coupled with x-ray analysis technology, particle composition can also be determined and classified. Since particle analysis influences many of the choices manufacturers make about how products are combined, having a top-of-the-line particle characterization tool becomes necessary.

Responding to trends put forth by these manufacturers, Aspex has created the industry’s only totally integrated solution for the automated detection, identification, and characterization of micron-level debris, specifically designed with the automotives manufacturing and cleansing operations in mind. The Aspex Personal Scanning Electron Microscope (PSEM) with Advanced Quality Control (AQC) software is revolutionizing the way particles are being detected, using its industrial electron beam analyzers to quickly scan and identify particles, insuring product cleanliness protocols are being upheld.

The Aspex PSEM with AQC software can help manufacturers identify, size, and characterize particles that could otherwise lead to product failure, and can reduce automakers manufacturing and warranty failures by upwards of 30%. With an easy to use interface and plenty of analysis options, the PSEM by Aspex is changing the way manufacturers look at particles characterization.

Reference:
Aspex, http://www.aspexcorp.com/industries/industrial-automation.html
ASTM, http://www.astm.org/Standards/E1617.htm

There are many ways to identify particles; however, none have the range and quality of a scanning electron microscope (SEM). SEMs are capable of superior magnification range, depth of field, and powerful contrast mechanisms when compared with other particle analyzers such as optical microscopy or laser diffraction. When coupled with X-ray technology, SEMs offers rapid and unambiguous classification of particles by elemental composition. To meet the demands of the automobile industry in its quest for better quality control, Aspex has created the industry’s only totally integrated solution for particle identification and characterization: the Advanced Quality Control (AQC).

The AQC for the Aspex Personal Scanning Electron Microscope (PSEM) allows manufacturers to detect and characterize particles directly on the shop floor. Utilizing its electron beam to search for inclusions, the AQC is capable of identifying particles from the millimeter to the sub-micron range. Once identified, the energy dispersive x-ray (EDX) analyzes the particles to provide elemental composition data. Manufacturers can take this information and assess where the source of the contamination is and take steps to eliminate or reduce the contamination. By allowing manufacturers easy access to microscopic information, they can adjust the quality control plans to produce higher-quality products.

Whether due to mechanical wear pieces flaking off, unwanted additives entering the line, or imperfections in materials, contamination is difficult to eliminate completely. The automobile industry is taking quality control steps to ensure product quality standards are being met. Aspex is helping manufacturers meet these goals with its PSEM and AQC software by allowing them to analyze materials on the shop floor with the ease of a fully-automated system for particle analysis. The PSEM with AQC can help reduce manufacturing and warranty failures by upwards of 30% in systems such as transmissions, power steering, and fuel injectors, creating a better product with better components.

Reference:
Aspex, http://www.aspexcorp.com/industries/industrial-automation.html