Pharmaceutical quality standards are regulated and / or guided by multiple bodies. In the United States, regulatory principles are laid out in the Code of Federal Regulations (CFR) describing certain requirements (e.g., 21 CFR 11, 58, 210, 211 sections), with regulatory guidances and directives published by the Food and Drug Administration (FDA) that also reference and utilize methods and practices published by the United States Pharmacopeia and National Formulary (USP / NF) along with incorporating sections of the International Conference of Harmonisation [Harmonization] (ICH).
The current FDA guidance for pharmaceutical drug products is “Analytical Procedures and Methods Validation for Drugs and Biologics” (July 2015); and “Bioanalytical Method Validation Guidance for Industry” (May 2018). The previously referenced guidance had been the USP chapter on validation (1225), however, that has been renamed to “validation of compendial procedures” and is no longer directory applicable for non-compendial products.
SLAP is an acronym for SELECTIVITY, LINEARITY, ACCURACY and PRECISION – the principle building blocks of validation.
Specificity
This is the verification of WHAT is being measured – the ability to establish the uniqueness of a component of interest. Its purpose to verify that the test method can measure the correct chemical component. This is often accomplished by utilizing multi-point detection (e.g., multiple wavelengths, LC-MS). This differs from selectivity, which represents the ability to isolate a component but does not necessarily establish that it is correct. Simple selectivity requires corroborating detection or an orthogonal methodology to achieve specificity.
Linearity
This is the measure of responsiveness for the test method. Parameters associated with this include Range, Sensitivity (i.e., Limit of Detection, Limit of Quantitation) and associated linearity curve fitting coefficients (e.g., 1st order, 2nd order, cubic, intercept, confidence intervals).
Accuracy
This is the verification of the correctness of the measure – the ability to hit the correct target. This is often described as percent recovery of the expected target values from linearity and precision measurements.
Precision
This is the measure of consistency in hitting the target, correct or not. Precision has been broken done into three types per ICH guidelines – REPEATABILITY – precision inherent to the test method; INTERMEDIATE PRECISION – precision between analysts, instruments, days and conditions; and REPRODUCIBILITY – precision between different laboratories, sites or groups.
Some of these terms and recommended standards will vary between guidances, method and validation types, but the general principles remain.