Contaminant clearance

Contaminant-clearance validation studies are of special signibcance in biopharmaceutical manufacture. As discussed in Section 7.6.4, downstream processing must be capable of removing contaminants such as viruses, DNA and endotoxin from the product steam. Contaminant-clearance validation studies normally entail spiking the raw material (from which the product is to be purihed) with a known level of the chosen contaminant and subjecting the contaminated material to the complete downstream processing protocol. This allows determination of the level of clearance of the contaminant achieved after each purihcation step, and the contaminant reduction factor for the overall process. 

Meconium staining of amniotic fluid increases the with a broad and variable peak at 400 to 415 nm. There is no way to compensate quantitatively for meconium contamination. Clearance of meconium from a single episode of passage into the amniotic fluid requires about 3 weeks. 

Contaminant/Impurity Clearance. Classes of contaminant removal include process-related, host-cell related, andproduct-related (e.g., aggregates,deaminations, and oxidations) substances [14]. Contaminant clearance studies can be used to avoid lot-to-lot acceptance criteria because safety margins of several logs of excess clearance are demonstrated [33]. In these studies, a contaminant is added to the input feed stream at the small scale, its recovery is measured at each stage of the... 

Grade C, Type II is typical of Hquid oxygen used as a rocket propellant oxidizer. Particulate content is limited because of the critical clearances found in mechanical parts of the rocket engine. In addition to water, acetylene and methane are limited because, on long standing, oxygen evaporation could cause concentration of these combustible contaminants to reach hazardous levels. 

Clearance samples Samples taken following a lead, asbestos, or other removal action, which must indicate the contaminant concentration to be at or below a specific level before the area can be cleared for normal occupation and work activities. 

Oil foaming Out-of-round shaft Excessive shaft deflection Uneven shimming of Contamination housing with loss of clearance Operating beyond grease life... 

For more comprehensive validation studies, the molecular mass profile of the DNA spike should roughly approximate to the molecular mass range of endogenous contaminant DNA in the crude product. Obviously, the true DNA clearance rate attained by downstream processing procedures (e.g. gel filtration) will depend to some extent on the molecular mass characteristics of the contaminant DNA. 

Fed PCB 133 at 550 mg/kg diet FW or PCB 197 at 530 mg/kg diet FW for 65 days, followed by a clean diet for 89 days, then reexposure to the contaminated diet for another 37 days No PCB clearance during initial exposure significant elimination of both PCBs when fed a clean diet. During reexposure, uptake efficiency for both PCBs was significantly higher than during the initial exposure 8... 

Both hexachloroethane and its lipophilic metabolites can distribute to body fat. Only hexachloroethane can be used to confirm compound exposure by way of a fat biopsy, since some of its metabolites are also produced from other chlorinated hydrocarbons or are present as contaminants in the environment. Based on one worker occupationally exposed to hexachloroethane, Selden et al. (1993) estimated that the plasma half-life in humans was several days, but less than one week. A clearance half-life in rats of 2.5 days was reported for hexachloroethane absorbed from the diet (Gorzinski et al. 1985). Therefore, similar to measurement of hexachloroethane in blood, urine, and feces, hexachloroethane in body fat is representative of current exposures rather than exposures that occurred weeks or months before testing. 

---