OOT

What is an OOT result?

OOT results may be within specification but show significant variation from historical results. The FDA and other regulatory agencies consider the integrity of laboratory data to be an integral part of the drug manufacturing process.1,2 Deficiencies of out-ofspecification (OOS) investigations continue to be the major cause of warning letters in the pharmaceutical industry. The regulatory agencies require that OOS, out-of-trend (OOT), or aberrant results be investigated.3 An effective and compliant quality management system will ensure thorough, timely, unbiased, well-documented, scientifically sound investigations for OOS, OOT, and aberrant results, which will ensure, if a root cause can be assigned, the implementation of appropriate corrective and preventative actions

OOT

OOS results are most often generated due to laboratory or manufacturing-related errors, the setting of inappropriate specifications, or poor method development. OOT results may be within specification but show significant variation from historical results. Aberrant results include unexpected variability in analytical results and system suitability failures. For example, % impurity value of 0.3 for earlyphase API lots did not meet criteria of 0.2, which was set based on research lots of 100g quantities; % assay value of 96.0 met the specification of 95.0-105.0 but was lower than historical values of 99.7, 99.4, 99.5, 98.9, and 99.5.
3

What need to be done for OOT?

Investigation like OOS Identify the root cause/assignable cause/probable cause Identify CAPA Implementation and data monitoring Do additional checks, if necessary Closure
4

FDA 483

Example of one FDA 483: Failed to recognize and investigate significant trends and special cause deviations in the quality characteristics of the starting material.