On October 30th, David Exline, Senior V.P. and Antonio Scatena, Laboratory Manager at Gateway Analytical hosted a webinar designed for laboratory and manufacturing personnel that encounter contaminants and foreign particulate matter in the manufacturing, process/product development and customer returns. This webinar discussed the process by which contaminants and foreign particles are isolated, identified, tracked to find the source of the issue, and then addressed to ensure that the issue does not arise again.
For more details on the webinar, you can use the links below.
We received a number of questions from attendees during the Q&A segment, and you can find those questions and answers below. If you have any questions about this or any other topic, please contact us.
- What sources might cause a contaminant of white particles where the chemical analysis shows high levels of silicate? Could a water station be the source of the issue? What stage would you recommend we start our investigation?
White particle contaminants can be from a variety of sources. White particles with high levels of silicates may be from dirt or possibly fillers. However, if the chemical composition is only silicon, it could be from a silicone source such as tubing. The confirmation of silicate vs. elemental silicon would be needed for clarification to determine where to start the source determination.
- Are you able to use terminal filters at points where a water station is used? If so, can it help to eliminate the probability of the water station being the source of the impurities?
Terminal filtration points are definitely beneficial in deterring downstream particulate contamination. However, one must be careful of the point at which the water is incorporated in order to ensure further containment has been addressed with the same amount of scrutiny.
- Could compressed air be a source of contamination and what is the accepted class of compressed air required for the production of pharmaceutical products?
Compressed air can certainly be a source of contamination, especially in cases where possible wear is occurring in the compression system.
- What are the typical sources for iron oxide contaminants?
Typical contaminants are rust, rouging and things containing pigment. Mold dope material for glass manufacturing also contains iron.
- Does our group that analyzes foreign particulate have to be GMP Compliant?
Yes. This is only way to ensure the proper training, equipment qualification and document control is in place.
- How do you determine particles that are less than 10 microns in size?
Sub-visible particulate are analyzed by methods that are designed to detect and characterize particles in that size range. The two most common are SEM/EDS and Raman spectroscopy.
- Is there a limit for particulates less than 10 microns in size?
Limits are determined by your own acceptance criteria that are established through a Quality by Design (QbD) process.
- How do you measure foreign particulate matter in nasal spray suspension products?
Foreign particulate are often counted by light or laser diffraction methods; however, chemical identification in conjunction with sizing is typically determined using automated SEM/EDS and automated Raman methods.
- What is the best testing method for identifying an unknown contaminant?
There is no turn-key analytical test for unknown contaminants. A multi-analytical approach combining optical microscopy with inorganic analytical testing methods (i.e. SEM/EDS) and organic analytical testing methods (i.e. FTIR and Raman) is most valuable for a complete characterization of particulate.
- How long does it take to fully identify something?
Depending on the methods needed for full characterization, the process may take minutes up to several hours to complete.
- What is the most common source material you find?
The most common sources of material we find are those common to the manufacturing process and environment. Examples of the most common are: hairs, fibers, stainless steel, silicone, rust, Teflon, raw materials and precipitated drug product.