Out of Specification – an Introduction

Quality control and consistent product quality are of utmost importance in the pharmaceutical industry. That is the why the investigation of OOS (out of specification) results is a critical aspect to review, when undergoing authority inspections. If the authority identifies flaws in the manufacturer’s handling of the OOS investigation, they may issue a no conformity to drug substance and drug product manufacturers. It is, therefore, crucial to conduct a proper investigation of OOS outcomes to avoid this consequence.

To ensure a comprehensive investigation, having a specific and adequate Out-of-Specification (OOS) Standard Operating Procedure (SOP) is crucial, as when analytical results fail to meet the pre-established acceptance criteria or the official pharmacopeial monograph specification range, they are considered OOS. Furthermore, these results can be observed in various stages of analysis, such as packing materials, raw materials, excipients, drug substances, final drug product testing, and stability study analysis. This is why you should improve your investigative process by implementing a robust OOS SOP.

To that extent, official guidance provides a standard for the industry on how to evaluate out-of-specification (OOS) test results and the term OOS. It also discusses on how to investigate OOS test results including the responsibilities of laboratory personnel, the laboratory phase, additional testing that may be necessary, when to expand the investigation outside the laboratory and the final evaluation of all test results.

Nevertheless, do not forget the main aim of the OOS investigation is to focus on the definite outcome of the root cause of the OOS result and that, with that aim, the OOS Standard Operating Procedure (SOP) is essential for concluding the investigation. Also, do not forget the investigation must be performed on time and be competent enough to conclude its root cause identification, impact evaluation, and find efficient corrective action and preventive action.

As a result, an action plan for the OOS Investigations must be conducted following the steps below:

1.            Phase I: Investigation includes primary investigations and extended laboratory investigations.

2.            Phase II: Investigation includes comprehensive manufacturing and sampling investigations.

3.            Phase III: Investigation includes extended manufacturing evaluation, resampling, and reanalysis of the samples.

All the activities within the investigations must be performed within a specific time, be thorough and very well written, so that they are clear and logical, but also need to be impartial, scientifically proven, recorded, properly documented, and reviewed by the quality assurance and regulatory affairs department. As a final note, remember that the practice of “retesting into compliance” is unacceptable and the number of retests should not be adjusted depending on the results obtained.

OOS is a demanding and vital part of your Quality, but did you know RC REDOL offers comprehensive cGMP support for the pharmaceutical industry, allowing you to focus on your activity with the guidance of dedicated and experienced Good Manufacturing Practices experts? Take your operations to the next level and bulletproof your Out of Specification procedures by contacting our team.

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