04-Jan-2025
Out of Specification Investigations Guidance - What You Need to Know
Summary
The US Food and Drug Administration (FDA) and the UK Medicines and Healthcare Regulatory Agency (MHRA) both publish Out of Specification Investigation Guidance documents for the pharmaceutical industry. Both regulatory bodies' guidances specify investigation processes that are virtually the same, with only minor changes that do not have a significant impact on the common approach being pushed. Following the procedures outlined in either is considered to be compliant with both, though it is helpful to be aware of the minor distinctions.- Author Company: ComplianceOnline
- Author Name: ComplianceOnline
- Author Email: sshastry@complianceonline.com
- Author Telephone: +18887172436
- Author Website: https://www.complianceonline.com
Editor: Ashutos Swain
Last Updated: 06-Jan-2025
The investigation approach should be the same for analytical results that are OOS, or indeed for any result that is outside the regular pattern of results, according to both US and UK regulations (often referred to as atypical results). It is critical that findings be trended in some form in order to identify OOT and anomalous results. This is usually performed by plotting release test results on a control chart, and for stability program outcomes by plotting the regression line.
Out-of-Specification (OOS) Result -
- Test result that does not comply with the pre-determined acceptance criteria (i.e. for example, filed applications, drug master files, approved marketing submissions, or official compendia or internal acceptance criteria).
- Test results that fall outside of established acceptance criteria which have been established in official compendia and/or by company documentation (i.e., Raw Material Specifications, In-Process/Final Product Testing, etc.).
Out of Trend (OOT) Result -
- Is generally a stability result that does not follow the expected trend, either in comparison with other stability batches or with respect to previous results collected during a stability study. However, the trends of starting materials and in-process samples may also yield out of trend data.
- The result is not necessarily OOS but does not look like a typical data point.
- Should be considered for environmental trend analysis such as for viable and non viable data (action limit or warning limit trends)
