# Out-of-specification investigations

Source: https://www.keypedia.com/records/uk_mhra_guidance/uk-mhra/1a7c68ac-4b0e-482a-80ff-0f1cf9e6406b
Type: Guidance
Published: August 27, 2013
Updated: February 26, 2018

> The Medicines and Healthcare products Regulatory Agency (MHRA) provides detailed guidance for pharmaceutical manufacturers on conducting Out-of-Specification (OOS) investigations. This regulatory framework is designed to ensure that any laboratory result failing to meet established quality criteria is thoroughly scrutinized before a product is released. While the document is a general standard rather than a report on a specific company or inspection date, it addresses the critical issue of how manufacturers handle unexpected test data. The guidance establishes a structured, three-phase approach to investigations. Phase I involves initial laboratory assessments to identify potential analytical errors. Phase II expands the scope to include a review of manufacturing processes, and Phase III concludes with a comprehensive evaluation of all findings to determine final batch disposition. To remain compliant, companies must maintain rigorous documentation and use scientific justification when investigating deviations. Required actions include performing deep-dive root-cause analyses and ensuring that batch release decisions are based on data integrity rather than a desire to ignore failing results. By following these multi-phase protocols, manufacturers can ensure that only safe, high-quality medicines reach the public, effectively mitigating risks associated with production inconsistencies.

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## Content

This Medicines and Healthcare products Regulatory Agency guidance for those carrying out of specification investigations covers: Laboratory analysis Results Phase Ia investigations Phase Ib investigations Phase II investigations Phase III investigations Batch disposition

## Attachments

- [Out of specification guidance](https://assets.publishing.service.gov.uk/media/5a82373b40f0b62305b93186/MHRA_OOS_OOT_Oct17.pptx)