Assays cleaning verification

Although swab selection is not included as a requirement in Table 15.3, it is a parameter that should be considered at some point in the development of a swab assay. From a practical view point, it could be evaluated once for a facility and then replicated on all other compounds. Cleaning verification methods for swabs... 

Although swab assays are different conceptually than both the impurity and the potency assay, the same scientific rationale governs the development of these assays. Many of the references listed in Table 15.4 outline different validation approaches. Seno outlined validation practices in the Japanese pharmaceutical industry for cleaning verification,23 and Kirsch outlined an approach for swab method validation that is consistent with ICH guidelines for method development.24 An important aspect of any cleaning-verification assay begins with swabbing the... 

Again the point is that, for any given molecule, the choice of analytical technique may vary. The techniques outlined below may, in general, provide the highest probably of technical success for very stringent acceptance limits. In addition, the techniques are listed in the order of preference for cleaning verification assays that would have an acceptance limit of 50ng/swab (most potent compounds in Table 15.2) or lower, and this will be the focus of the remainder of this chapter. 

In a work by Liu et al.,26 a cleaning-verification assay was validated for a highly potent family of compounds utilizing a swab-sampling procedure and LC-MS for separation and detection of the analytes. Due to the high potency of the compound, the LC-MS method was validated at a level of 50ng/25cm2 and 50 ng/100 cm2... 

In summary, LC-MS offers excellent sensitivity for many classes of pharmaceutical compounds. Due to the fact that MS is becoming more routine (i.e., it is essentially another detector), LC-MS should be the first consideration for all cleaning verification assays that are less than 0.1 pg/swab. In the citations outlined above, LC-MS has been shown to offer excellent sensitivity and specificity for the analytes of interest. The mass spectrometric conditions can be optimized in a flow injection mode to allow for rapid method development. All LC-MS analytical methods were validated in a way consistent with the requirements outlined in Table 15.3. The applications cited utilized LC-MS because of the sensitivity requirements of the safety acceptance limits however, if the molecule of interest poses unique detection challenges such as a poor chromophote, LC-MS should be considered for assays at the level of 1.0 ig/unit area, or less. Above 1.0 xg/unit area there may be more attractive options for these swab determinations. 

This chapter presented the challenges associated with cleaning verification assays for very potent compounds. Three different approaches to calculating acceptance limits... 

There are two types of analysis needed for cleaning verification (1) active (2) soap. Since residual amounts of active and soap are to be determined, the methods need to be very sensitive. For measuring the active, the assay or the content uniformity method can be employed (if the sensitivity of the existing method is acceptable). If the sensitivity of the current assay or content uniformity method is not acceptable, then modifications can be made to an existing method or a more sensitive test method is developed. 

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