Verification calibration

Part of the confusion surrounding the model testing and validation process is largely because different meanings have been attached to the terms calibration, verification, validation, and post-audit in the technical literature. As a result of the Pellston conference, I have adopted the following relationship among these terms ... 

The process of field validation and testing of models was presented at the Pellston conference as a systematic analysis of errors (6. In any model calibration, verification or validation effort, the model user is continually faced with the need to analyze and explain differences (i.e., errors, in this discussion) between observed data and model predictions. This requires assessments of the accuracy and validity of observed model input data, parameter values, system representation, and observed output data. Figure 2 schematically compares the model and the natural system with regard to inputs, outputs, and sources of error. Clearly there are possible errors associated with each of the categories noted above, i.e., input, parameters, system representation, output. Differences in each of these categories can have dramatic impacts on the conclusions of the model validation process. 

Quality controls are single procednres that are performed in conjnnction with an analysis to help assess the snccess of the analysis in a qnantitative manner. Examples of qnality controls are blanks, calibration, calibration verification. 

Unfortunately, and probably unavoidably, from the earliest research until the present, investigators have not used the same standardization process. Furthermore, standardization practices within different research groups have only rarely followed the meticulous series of in-house calibrations, verifications, and interlaboratory comparisons long prescribed by the conununity of measurement specialists. Several quantitatively crucial studies, however, have followed sound measurement procedures (see, e.g.. Chapter 9). 

Record the first thermal cycle (used for calibration verification) by heating the sample at a rate of 10°C/min under nitrogen atmosphere from ambient to 30°C above the expected melting point or glass transi-... 

An initial calibration verification standard should be measured after calibration and before measuring any sample. A calibration verification standard is a standard solution or set of solutions used to check calibration standard levels. The concentration of the analyte should be near either the regulatory level of concern or approximately at the midpoint of the calibration range. These standards must be independent of the calibration solutions and be prepared from a stock solution with a different manufacturer or manufacturer lot identification than the calibration standards. An acceptance criterion is set, usually as a maximum allowable percentage variation (e.g., 5%, 10%). The calibration can be continually verified using either a calibration standard or the initial calibration verification standard. Acceptance criteria must be set and action taken when results fall outside the limits (i.e., stop the analysis, investigate, correct the problem and rerun samples run between the verification standards that were not limits). 

Once a full instrument calibration is in place, it is not always necessary to repeat the full calibration procedure when the instrument is next used. Instead of a full calibration, a calibration verification can be performed by infusing the calibration solution and setting all peak matching parameters to the values that were used... 

Resolution is also affected by the actual time that ions spend in the quadrupole. Ions that have higher kinetic energy have shorter residence time and lower resolution. Reducing the kinetic energy typically leads to an improvement in resolution. A dramatic change in resolution may cause a shift in the instrument calibration. After adjusting the resolution, it is necessary to check the calibration (calibration verification), and if it is noted that the difference between the predicted and actual mass values have shifted, the instrument should be recalibrated. 

Fit the purpose calibration. It is common sense to check instrument performance each day, and GLP requirements simply formalize the performance and documentation of these checks. On the other hand, it is also important to use the right test (full calibration, verification, system suitability test, or instrument and method validation) to verify the performance and to avoid needlessly lengthy procedures. As already discussed (see Sections 13.2.3 and 13.3.1), it is not always necessary to perform a MS full calibration every day. For example, if a particular MS is used only to record complete full-scan mass spectra, a daily calibration or verification of the calibration of the m/z ratio scale is required. However, in the case where a MS is coupled with an LC and utilized primarily for the analysis of one or more analytes in the selected ion monitoring (SIM) mode, it does not always require a daily verification of the calibration. In this specific case it is quite common in LC-MS and LC-MS/MS applications to test only the following performance parameters (a) sensitivity, (b) system precision,... 

Verification of test equipment calibration Verification of controls and indicators Computer control system testing Verification of sequence of operations Verification of major components operation Verification of alarms Power failure/recovery testing... 

After initial calibration has been completed, it must be verified with a second source standard, which has been prepared from material coming from a different source (different manufacturer or lot number). This QC measure, called the second source confirmation, allows detecting errors in the initial calibration standard solution preparation and prevents a systematic error in compound quantitation. Only after this initial calibration verification (ICV) standard has also met its own acceptance criteria may the analyst start analyzing samples. 

After a sample sequence has been analyzed, the analyst evaluates a computer printout with the raw analytical data and the computer-calculated analytical results. The analyst verifies that the QC acceptance criteria for daily calibration verifications, the surrogate and internal standards, and laboratory QC samples have been met. This review enables the analyst to determine whether reanalysis of samples will be required. Sample dilutions may be also needed if analyte concentrations in samples exceed the instrument calibration range. 

Laboratories must perform initial calibration prior to the start of sample analysis and confirm its validity throughout sample analysis with calibration verification checks. 

Linear calibration verification is always performed with a single ICV standard. Non-linear calibrations may require two ICV standards analyzed at different inflections of the curve. 

Rule 3. Continuing calibration verification must take place at regular intervals during... 

A continuing calibration verification standard at a concentration that is close to the midrange of the calibration curve may be prepared either from the same stock solution as the initial calibration standard or from a standard of a different source. This CCV standard is analyzed at a certain frequency throughout sample analysis. 

Initial calibration verification with a second Continuing calibration... 

External standard calibration is used if the changes in the analytical system that may occur from the time the instrument has been calibrated to the time the sample analysis is completed are negligible. These changes are assumed to produce an insignificant error that is built into the daily calibration verification acceptance criteria. The response (calibration) factor of the external standard calibration is calculated according to Equation 1, Appendix 22, and it is measured in concentration or mass units (or their inverse). 

Initial and continuing calibration verifications and acceptance limits Raw data for each sample (including reanalysis and second column confirmation), blanks, LCS/LCSD, MS/MSD, and calibration standards Sample preparation bench sheets Gel permeation chromatography clean-up logs / (Summary only) ... 

Initial and continuing calibration verifications and acceptance limits S S (Summary only) ... 

Chemical Abstract Service calibration check compounds continuing calibration verification California Code of Regulations... 

IATA ICAP ICP ICP-AES ICP-MS ICV ID IDL IDW ISO International Air Transportation Association inductively coupled argon plasma inductively coupled plasma inductively coupled plasma-atomic emission spectrometry inductively coupled plasma-mass spectrometry initial calibration verification identification instrument detection limit investigation-derived waste International Standardization Organization... 

Platinum resistance thermometers are currently used by the NIST for calibration verification of other thermometer types for the temperature range 13.8 to 904 K. In addition, they are one of the easiest types of thermometers to interface with a computer for data input. On the other hand, platinum resistance thermometers are very expensive, extremely sensitive to physical changes and shock, have a slow response time, and therefore can take a long time to equilibrate to a given temperature. Thus, resistance thermometers are often used only for calibration purposes in many labs. 

Requalification should be done in accordance with a defined schedule. The frequency of requalification may be determined on the basis of factors such as the analysis of results relating to calibration, verification and maintenance. 

---