Passive sampling data validation

The advantages of the in situ techniques include an intact blood supply multiple samples may be taken, thus enabling kinetic studies to be performed. A fundamental point regarding the in situ intestinal perfusion method is that the rat model has been demonstrated to correlate with in vivo human data [46 19], Amidon et al. [36] have demonstrated that it can be used to predict absorption for both passive and carrier-mediated substrates. However, the intestinal luminal concentrations used in rat experiments should reflect adequately scaled and clinically relevant concentrations to ensure appropriate permeability determinations [50], There are limitations of the in situ rat perfusion models. The assumption involved in derivation of these models that all drug passes into portal vein, that is drug disappearance reflects drug absorption, may not be valid in some circumstances as discussed below. 

However, cause-and-effect relationships in these situations are obscured by rampant variability and multiple mysterious causes. The approach is passive. Classical observational tools for industry usually include sampling plans, control charts, and process capability studies. In addition, Branning has found two of the most useful observational tools for validation and PAT are process flow charts and fishbone diagrams, which help define the process and identify the potential sources of variability. These observational tools need to be used on a routine basis to collect background data for validation and PAT. 

B. Passive Monitors—Ethylene oxide diffuses into the monitor and is collected in the sampling media. The DuPont Pro-Tek badge collects EtO in an absorbing solution, which is analyzed colorimetrically to determine the amount of EtO present. The 3M 350 badge collects the EtO on chemically treated charcoal. Other passive monitors are currently being developed and tested. Both 3M and DuPont have submitted data indicating their dosimeters meet the precision and accuracy requirements of the proposed ethylene oxide standard. Both presented laboratory validation data to 0.2 ppm (Exs. 11-65, 4-20, 108, 109, 130). 

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