Viable particles

Fig. 2-3. Grand average number (N), surface area (S), and volume (V) distribution of Los Angeles smog. The linear ordinate normalized by total number (NT), area (ST), or volume (VT) is used so that the apparent area under the curves is proportional to the quantity in that size range. Source Corn, M., Properties of non-viable particles in the air. In "Air Pollution," 3rd ed., Vol. I ( A. C. Stern, ed.). Academic Press, New York, 1976, p. 123.

Environmental controls/monitoring programs includes viable and nonviable particles, surface-viable particles and personnel (filling areas) schedules and action/product disposition media fills cover all shifts and operators, all package sizes and worst-case assessments. 

A cleanliness classification in accordance with the latest revision of ISO 14644 is generally inadequate by itself to describe a facility used for pharmaceutical processes. The presence of viable particles (living organisms) within the particle count achieved by applying methods described in the standard may affect the product within the facility. A measure of both viable and nonviable particles is required to provide sufficient information upon which to base a decision regarding the suitability of the clean room for its intended purpose. 

Ljungqvist, B. Reinmiiller, B. Active sampling of airborne viable particles in controlled environments a comparative study of common instruments. Eur. J. Parenter. Sci. 1998, 3 (3), 59-62. 

The efficacy of the filters through which the air is passed should be monitored at predetermined intervals. Air quality may be monitored by volumetric air sampler or settle plate. Table 21.2 describes the maximum concentrations of non-viable particles and viable airborne microorganisms permitted in the four grades of air. 

Jacobson, A.R. and Morris, S.C., 1976. The primary air pollutants viable particles, their occurrence, sources and effects, in Air Pollution. 3rd ed.. Stern, A.C., Ed., Academic Press. New York. 

Nanoparticles Nanoparticles can be formed from surfactants, polymers, or polyamino acids. The concept is mainly that viable particles are formed, they can maintain their shape and use during preparation, they are stable, and the particles formed are in the nanometer range. An example of nanoparticles is the Medusa concept by Flamel Technologies. 

To determine dose (or assay) the quantity of the compound is assessed in the most specific way by HPLC or specific capillary electrophoresis methods using authenticated reference/working standards for quantitative evaluation are suitable for many products. In the case of viral or cell therapy, total protein determination or number of viable particles or (specific) cells might be appropriate dose definitions. In addition, DNA hybridization assays or the determination of total DNA can be applied. Alternatively, for some products a dose definition may be based on the potency of the applied amount. 

Some or all of the principles of aseptic manufacture are used in the manufacture of terminally sterilized products. There are two main reasons for this. The first is micTobiological. The numbers and types of microorganisms present in or on a product item prior to sterilization make up a major determinant of sterility and merit serious consideration. The second reason is the avoidance of large non viable particles in parenteral products. 

The definitions of air quality categories l-V are given in table 3. The categories have been defined according to their permitted levels of viable and non viable particles. For comparative purposes, the requirements of the different environmental classifications from commonly quoted standards documents are also included in the table. 

Viable particle monitoring for micro-organisms and non-visible particle monitors should be performed at regular intervals. 

VIABLE PARTICLE A discrete physical particle that contains one or more viable microorganisms. A viable particle may be an inert particle (dust, lint) which has one or more adherent viable microorganisms it may consist of an aggregate of two or more viable cells or it may be simply a single viable cell. Because of collection and testing limitations, most air samplings indicate a contamination level somewhere between the number of viable particles in the air and the actual number of viable microorganisms in the air. 

The most common collection methods rely on impaction, the same process as described in Section 5.5 for nonbioaerosols. Slit impactors impact particles directly onto a culture medium. For bacteria and fungal spores, the culture medium, called agar, is a semisolid material containing water and nutrients that foster the growth of the viable particles that are collected. For viruses, cell or tissue culture media are used. Typically, the agar fills a 100-mm or 150-mm disposable petri dish, called a culture plate, that is slowly rotated under the slit to provide a history of bioaerosol concentration. Rotating slit impactors have flow rates of 28-50 L/min and cutoff diameters of about 0.5 pm. 

Total number of viable particles collected equals the number of filled sites times the conection factor. 

A 400-jet impactor samples a bioaerosol at 28 L/min for 20 minutes. If 344 colonies are counted, what is the average airborne number concentration of viable particles. Assume no loss of viability during sampling. 

This chapter does not attempt to review the entire range of clearance mechanisms provided by the respiratory tract for all kinds of deposited particles. It does not address the clearance of particles that are readily soluble in the epithelial lining fluid, nor specific immune reactions triggered by viable particles. It reviews clearance mechanisms of particles deposited in the lung, with emphasis on slow-clearance mechanisms. 

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