Subvisible particles

Particulate matter is viewed as unacceptable contamination in parenteral solutions. It is recognized that subvisible particulate matter will exist in certain amounts, but the USP now has limits for acceptable levels of particulate matter for SVIs (no more than 6000 particles per container >0.5 pm no more than 600 particles per container >25 pm). The USP is the only compendium in the world that contains limits for subvisible particulates in SVIs. All worldwide compendia have subvisible particle limits (particles per milliliter) for large-volume injections. SVI solutions with visible particulate matter should not used. Particulate matter creates problems in product quality and clinical safety. The primary sources of particulate matter are the container-closure systems and personnel. 

Particulate matter testing. Particulate matter testing will normally include limits for visible particulates and/or clarity of solution, as well as for subvisible particles. 

Contrast chemistry. (I mean classical chemistry, not work conducted in chemistry departments that is really physics.) It is very concrete, having to do with what various familiar substances are made of. As far as I know, it is untouched by politics at least I have not heard of Marxist chemistry or feminist chemistry. The classical chemical equations are the best-confirmed and most robust theoretical generalizations known to science, and they dramatically explain myriads of striking macrophenomena. No working chemist would think of denying that familiar substances are composed of molecules, which, in turn, are very uniform and regular constellations of atoms, or that atoms are tiny subvisible particles. It would be hard to take an instrumentalist attitude toward hydrolysis. 

In addition, other tests specific to the drug substance and formulation may apply, such as sterility, microbial limits, bacterial endotoxin, and pH. These types of tests would also be called for in order to comply with local pharmacopoeial requirements. Tests for subvisible particles beyond what is required in the pharmacopoeia may also be necessary due to immunogenicity concerns [29]. 

Overlooking subvisible particles in therapeutic protein products gaps that may compromise product quality. J pharm sd (early view) 1-5. 

Carpenter JF, Randolph TW, Jiskoot W, Crommelin DJA, Middaugh CR, Winter G, Fan YX, Kirshner S, Verthelyi D, Kozlowski S, Clouse KA, Swann PG, Rosenberg A, Chemey B. Overlooking subvisible particles in therapeutic protein products gaps that may compromise product quality. J Pharm Sci 2009 98 1201-1205. 

Singh SK, Afonina N, Awwad M, Bechtold-Peters K, Blue JT, Chou D, Cromwell M, Krause HJ, Mahler HC, Meyer BK, Narhi L, Nesta DP, Spitznagel T. An industry perspective on the monitoring of subvisible particles as a quality attribute for protein therapeutics. J Pharm Sci 2010 99 3302-3321. 

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