Calibration and Validation, Slides of Pharmaceutical Analysis

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Calibration and Validation

Calibration

• Instrument calibration is one of the primary processes used to maintain instrument accuracy. Calibration is the process of configuring an instrument to provide a result for a sample within an acceptable range by eliminating or minimizing factors that cause inaccurate measurements.
• Above all, Calibration is the measurement technology to compare between values obtained by a device under test with those of a calibration standard of known accuracy.
• Calibration involves measuring and adjusting the instrument response using known standards. Performance verification verifies the operation and performance characteristics of an instrument against a predetermined set of requirements. Calibration is a part of performance verification.

Calibration Vs. Validation

Validation parameters

Accuracy

• The degree of closeness of the determined value to the known true/standard value under prescribed conditions. This is sometimes termed trueness.
• For example, if in lab somebody obtains a weight measurement of 3. 2 kg for a given substance, but the actual or known weight is 10 kg, then your measurement is not accurate. In this case, measurement is not close to the known value.

Precision

• The precision of an analytical procedure expresses the closeness of agreement (degree of scatter) between a series of measurements obtained from multiple samples of the same homogeneous sample under prescribed conditions.
• For example, using the example above, if you weigh a given substance five times, and get 3. 2 kg each time, then your measurement is very precise.
• Precision is independent of accuracy.
• You can be very precise but inaccurate, as described above.
• You can also be accurate but imprecise.

Precision

Precision is usually investigated at three levels:

• Repeatability
• Intermediate precision and
• Reproducibility
• Repeatability (Precision): Repeatability is a measure of the precision under the same operating conditions over a short interval of time. Above all, Repeatability is the variation in measurements taken by a single person or instrument on the same item, under the same conditions, and in a short period of time. Such variability can be caused by, for example, intra-individual variability and intra-observer variability. A measurement may be said to be repeatable when this variation is smaller than a pre- determined acceptance criterion.

Precision

• Intermediate Precision: Intermediate precision is defined as the variation within the same laboratory. The extent to which intermediate precision needs to be established depends on the circumstances under which the procedure is intended to be used.
• Reproducibility: Reproducibility is the ability of an entire analysis of an experiment or study to be duplicated or getting the same/closed result for multiple operations, either by the same researcher or by someone else working independently, whereas reproducing an experiment is called replicating it.

Specificity

• Specificity is the ability to assess unequivocally an analyte in the presence of components that may be expected to be present.
• In many cases, selectivity and specificity are often used interchangeably.
• The specificity of a test method is determined by comparing test results from an analysis of samples containing impurities with those obtained from an analysis of samples without impurities.

Quantification range

The range of concentration, including ULOQ and LLOQ that can be quantified reliably and reproducibly with accuracy and precision through the use of a concentration–response relationship.

Quantification limit (LOQ)

The quantification limit of an individual analytical procedure is the lowest amount of analyte in a sample that can be determined quantitatively with suitable precision and accuracy.

Inter-relationship between qualification and

validation

Inter-relationship between qualification and validation

Interrelationship between qualification and

validation

• Performance Qualification: Performance qualification (PQ) is a process to demonstrate that an instrument can fulfill the requirements outlined in the user requirements.
• Change Control: A statement of the company's commitment to controlling critical changes to materials, facilities, equipment or processes (including analytical techniques), should be included.

Validation master plan (VMP)

• A Validation Master Plan is a document that summarizes the company's overall philosophy, intentions and approach to be used for establishing performance adequacy.
• Validation master plan = Design qualification (DQ) + Installation qualification (IQ) + Operational qualification (OQ) + Process Validation or Performance qualification (PQ). VMP= DQ+IQ+OQ+PQ Format and Content
• The VMP should be a summary document and should therefore be brief, concise and clear. It should not repeat information documented elsewhere but refer to existing documents such as Policy Documents, SOP's and Validation Protocols. The VMP should be agreed by management.