Identification of Particles in Parenteral Drug Raw Materials

Abstract

The presence of particles in drug products is regulated. These particles may be present before the beginning of the manufacturing process—that is, from the raw materials. To prevent the inclusion of these particles, it is important to understand their composition and origin, so that raw material quality, processing, and shipping can be improved. Thus, it is important to correctly identify particles seen in raw materials. Raw materials need to be of a certain quality with respect to physical and chemical composition and need to have no contaminants in the form of particles, which could contaminate the product or indicate that the raw materials are not pure enough to make a high-quality product. Particles are often seen when handling raw materials because of their different color, size, or shape characteristics. Particles may appear to be very different to the eye than they actually are, so microscope, chemical, and elemental analyses are required for accuracy in proper identification. This paper shows how using three different spectroscopy tools correctly and together can help identify particles from extrinsic, intrinsic, and inherent sources. Particles can originate from material sources such as humans and the environment (extrinsic), from within the process (intrinsic), and as part of the formulation (inherent). Microscope versions of Raman spectroscopy, laser-induced breakdown spectroscopy, and infrared spectroscopy are excellent tools for identifying particles, because they are fast and accurate techniques needing minimal sample preparation that can provide chemical composition, as well as images, that can be used for identification. The micro-analysis capabilities allow for easy analysis of different portions of samples, so multiple components can be identified, and sample preparation can be reduced. Using just one of these techniques may be insufficient to give adequate identification results so that the source of contamination can be adequately identified. The complementarity of the techniques provides the advantage of identifying various chemical and molecular components, as well as elemental and image analyses. Correct interpretation of the results from these techniques is also very important.

LAY ABSTRACT: The presence of particles in drug products is regulated. These particles may be present before the beginning of the manufacturing process—that is, from the raw materials. To prevent the inclusion of these particles, it is important to understand their composition and origin, so that raw material quality, processing, and shipping can be improved. Thus, it is important to correctly identify particles seen in raw materials. Raw materials need to be of a certain quality with respect to physical and chemical composition and need to have no contaminants in the form of particles, which could contaminate the product or indicate that the raw materials are not pure enough to make a high-quality product. Particles are often seen when handling raw materials because of their different color, size, or shape characteristics. Particles may appear to be very different to the eye than they actually are, so microscope, chemical, and elemental analyses are required for accuracy in proper identification. This paper shows how using three different spectroscopy tools correctly and together can help identify particles from extrinsic, intrinsic, and inherent sources. Particles can originate from material sources such as humans and the environment (extrinsic), from within the process (intrinsic), and as part of the formulation (inherent). Spectroscopy uses light to identify materials. This paper shows how using three different spectroscopy tools correctly and together can be used to identify particles from extrinsic, intrinsic, and inherent sources. These were Raman, laser-induced breakdown, and infrared spectroscopies. These techniques are excellent tools for identifying particles, because they are fast and accurate techniques needing minimal sample preparation that can provide chemical composition, as well as images, that can be used for identification. Versions of these that use micro-analyses capabilities allow for easy analysis of different portions of samples, so multiple components can be identified, and sample preparation can be reduced. Each technique has different capabilities that complement each other, and using all three provides the advantage of identifying various chemical and molecular components, as well as elemental and image analyses. However, each of these has limitations and different capabilities that make having them all available for analyses important. Also, it is very important to be able to correctly interpret the results from the instruments.