Application of improved standardization methods and instrumentation in the USP particulate test for SVI.

The USP (788) requirement for particulate matter in small volume injections (SVI) became effective January 1, 1986. The standardization component of the requirement is time-consuming and open to subjective interpretation. Current generation light obscuration (LO) counters offer many advantages over those available when (788) was implemented. Significant improvements may be made to the requirement by optimizing the counter standardization procedure and making provisions for use of newer instrumentation. Key improvements to (788) suggested by our experience with the SVI test method include: (1) revision of the requirement to include a time-effective stand-alone standardization procedure; (2) provision for use of currently marketed LO counter systems; (3) development of new standard materials including a count standard; and, (4) deletion of the present requirement for validation of LO counts by microscopy. Significant user advantages accruing to an improved methodology and the use of new instrumentation will include decreased time spent in standardization, lower variability of data between different laboratories, and less instrument down time.

Method evaluation: automated microscopy as a compendial test for particulates in parenteral solutions.

Accurate enumeration and sizing of contaminant particles in parenteral solutions are critical to the assessment of product quality and suitability for patient use. Current manual microscopic and instrumental (light obscuration) methodologies specified by the USP both result in data of high variability. The microscopic assay for large volume parenterals is time consuming and incorporates an undesirable level of subjectivity; light obscuration counters tend to undersize larger particles and fibers and have low detection efficiency for some particle types commonly present in small volume injections. Light microscopic image analysis is proposed as a method which combines the best features of the two present methods and allows an accurate, precise, and cost effective analysis of parenteral contaminant particles. This paper briefly summarizes the principles of microscopic image analysis and discusses its application in concert with optimized sampling and counting techniques as an improved compendial methodology. Instrument performance requirements are discussed with reference to a number of currently available image analysis systems.