Clearance capacity

More recently, Harner et al. (2003) coated ethylene vinyl acetate (EVA) onto glass (polymer coated glass [POG]) for use as fugacity sensors or equilibrium samplers of SVOCs in indoor and outdoor air. The EVA film fhickness was 1.1 and 2.4 qm depending on the application and as expected, SVOC sorption capacity and times to equilibrium were shown to be directly proportional to film thickness. The clearance capacity Ey volume of sample medium cleared of chemical) of a sorbent for an analyte is given by... 

Targeting to SECs should be directed at specific receptors present on this ceU type. A wide range of proteins and other molecules can be taken up by SECs through receptor-mediated endocytosis. For example, SECs play an important role in the uptake of degradation prodncts of the extracellular matrix. For this purpose they have hyaluronan [6], (pro)coUagen, and fi-bronectin receptors [7]. The first two receptors are nniqnely located on SECs. Elevated levels of serum hyaluronan and fibronectin, that are often fonnd in Uver disease [8], are nsnally the result of dysfunction of the clearance capacity of SECs combined with an increased production by HSCs [9]. 

Hayes(Ref 2,p 605) and TM 9-1980(Ref 9,p 55) classify the inert bombs as practice, drill and gage. The use of practice bombs is for the same purpose as the practice bomb described in TM 9-1900(Ref 15,p 171), while the use of the drill bomb is the same as that of the dummy bomb of Ref 15,p 172. The gage bomb serves for gaging and testing new types of airplanes for clearance, capacity and functioning of bomb racks. Such bombs are not issued to the field services... 

The virus reduction factor of an individual purification or removal—inactivation step is defined as the log10 of the ratio of the virus load in the pre-purification material divided by the virus load in the post-purification material. A clearance factor for each stage can be calculated and the overall clearance capacity of the production process assessed. Total virus reduction is calculated as the sum of individual log reduction factors. Individual manufacturing steps must possess fundamentally different mechanisms of virus removal or inactivation in order for values to be considered cumulative. Additionally, because viruses vary greatly with regard to inactivation or removal profiles, only data for the same model virus can be cumulative. 

As emphasized in Chapter 23, neonates are especially vulnerable to ADRs because they are sometimes exposed to drugs before birth and have immature renal and hepatic drug clearance capacities. Additionally, there is insufficient information on the clinical pharmacology of various drugs in this age group to guide rational pharmacotherapy (38, 39). 

Virus validation studies assess the virus clearance capacity of a process and the evaluation and interpretation of virus clearance data from terminal inactivation and upstream process steps are similar. Limitations in the design and execution of virus validation studies may lead to an incorrect estimate of the ability of a process to inactivate/remove virus infectivity. The three terminal inactivation treatments discussed here illustrate the importance of rigorously controlling virus validation studies. 

Troth, D., Aoki, M., Pasinelli, P., Berger, U.V., Danbolt, N.C., Brown, R.H., and Hediger, M.A. (2001) Amyotrophic lateral sclerosis-linked glutamate transporter mutant has impaired glutamate clearance capacity. Journal of Biological Chemistry. 276, 576-582. 

Each lot of unprocessed bulk drug derived from mammalian cell culture (e.g., the harvesf) should be assessed for bioburden, and shown to be free of adventitious vimses and mycoplasma as described in ICH Q5A. Titers of endogenous retrovims (e.g., type C particles) in chnical lots and at least the first three consistency lots should be quantified for comparison to the validated clearance capacity of the purification process [5.] Generally, the quantification of retrovirus in the unprocessed hulk drug is carried out using transmission electron microscopy (TEM), though quantification by validated real time PCR methods is also acceptable [5, 37]. 

The capacity of a pnrification process to clear viruses is demonstrated at a representative small scale nsing model viruses. The most common model viruses used in this validation study are xenotropic murine leukemia virus (x-MuLV), mouse minute virus (MMV), and reovirus (Reo). The viral clearance capacity of the chromatographic steps, inactivation steps, and the viral filnation step is demonstrated by spiking a known amount of a model virus into the load of each of these unit operations and calculating the efhciency of removal by measuring the remaining viral titer in the product containing fractions. 

Minimum clearance/ capacities Pump High reach (TLHP)... 

---