Out of Specification Guidance

The issue faced when dealing with out of specification (OOS) results is as much a challenge now as it ever was. Without doubt the most common deficiency raised, is the one where the OOS result has been invalidated on the basis of assumptions and theories with no real evidence to support the decision.

My name is Lesley Graham and I’ve been conducting GMP inspections of contract laboratories for the past 13 years. During this time I’ve reviewed many an investigation into determining whether the out of specification result is true or if there is an assignable cause.

The MHRA first published guidance to industry on how to handle OOS investigations in August 2013. When the guidance was first released there was some what of a mixed reaction. Mainly because the guidance is in the form of a flow chart, so it didn’t look like other guidance and there was next to no focus on how much repeat testing is enough. Up until that point the main approach to handling out of specification results was to repeat the testing a further two times and hope for 2 results that pass. This logic is flawed and definitely not based on sound scientific rational. The good news is that since the publication of the guidance those involved in conducting investigations have with mixed success, embraced the concept of hypothesis testing. Despite this being a signification shift in the right direction, there is still a way to go.  When a laboratory embarks on an investigation their biggest challenge is to move from a position of “I think this is the cause” to “I know this is the cause”. It was this challenge that gave rise to the idea for the presentations delivered in the GMP stream at the recent MHRA Labs Symposium.

How to inspect Laboratories was also the theme at the September 2017 PICS training event for inspectors. This event provided another opportunity on a global level to discuss the guidance and share how best it could be used.

The guidance offers a stepwise approach on what should be considered at the each stage of the investigation.  It has recently been reviewed and apart from some minor changes, mainly to do with ease of use, it is much the same.

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1 comment

  1. Comment by kishen kaul posted on

    very good - easy to understand and self explainatory


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