1) Section 5.9.1 of the Guidelines discusses use of CRMs and RMs as quality control samples. What level of traceability is required for an organism used as a QC sample/positive control to
determine method accuracy for microbiological tests, and how can the microbial count be determined?
The microbiological QCS organism is traceable from date of possession, preferably to a Type culture collection such as ATCC, NCTC, etc. The working culture is inoculated into an enrichment broth, and after a defined incubation period (ex. overnight), is diluted and the density is determined (e.g. by enumerating using non-selective media or by using a densitometer, spectrophotometer, McFarland standard or equivalent) to estimate the CFU/mL of inoculum. Once the density of the inoculum has been verified by one of these means, it may be used for either media QC or sample batch QC as a measure of relative recovery (note: inoculum density may be determined concurrently with testing).
2) Appendix A, Table 1 contains a requirement for weekly conductivity verification of DI systems. Does the requirement for weekly verification apply to the conductivity meter that is used to monitor the DI system?
The requirement for DI systems is for verification of the water. Requirements for verification of conductivity meters are contained in the Table 1 section on “pH meters, ion selective, and related conductivity equipment.” The laboratory sets an appropriate frequency for conductivity meter verifications with consideration of the criticality of the measurement (i.e., is it a reported result?) and accreditation body requirements.
3) Appendix A, Table 1 contains a requirement for weekly conductivity verification of DI systems. Does a continuous conductivity monitor meet the requirements of weekly monitoring?
Section 5.5.2 states that Appendix A, Table 1 provides minimum requirements. Greater frequencies or continuous will fulfill this requirement.
4) Appendix A, Table 1 contains a requirement to verify detector response of chromatographic systems with an analytical standard at mid‐range concentration with each batch. Does this allow for use of an analytical standard at the lower end of the calibration curve to match sample concentrations rather than at mid‐range of the calibration curve?
Table 1 sets a minimum requirement. Use of an analytical standard at a level below the mid‐range of the calibration curve is more difficult due to increased method variability as you approach the LOQ and would meet the minimum requirement of Table 1.
5) Appendix A, Table 1 contains a requirement for weekly conductivity testing of DI systems. Some laboratories may go more than a week without operation. Was the intent of the requirement to be “week of use”?
Yes, the intent is that the water be tested each week of use.
6) Does ALACC:2015 Section 5.9.1 require the use of a QCS (full method, in matrix and known value) for qualitative microbiological methods?
No. The first paragraph of Section 5.9.1 of the ALACC Guidelines provides a number of examples of quality control samples, but does not require the use of specific types in specific situations. The use of qualitative quality control samples (e.g., positive/negative controls) is suitable for qualitative methods.
7) Appendix A, Table 1 has a requirement that safety cabinets and laminar airflow cabinets “(if used for culture or sterility work)” must have an open media control during each use. What is considered “culture or sterility work”?
It is sterility work (i.e., sterility testing as defined by the USP) or culture work in support of sterility work. In these cases it is critical to minimize and detect cross contamination.
8) Appendix A, Table 1 contains a requirement for verifying autoclave pressure with each load. Does this mean pressure gauges and thermometers associated with autoclaves need to be calibrated?
Pressure gauges and thermometers associated with autoclaves do not require calibration, because the uniformity and stability requirements for autoclaves are sufficient to confirm proper performance.