Ask the Expert: Enhancing Out-of-Specification Procedures

Ask the Expert Video Series

Welcome to the Ask the Expert video series. This series is an extension of PharmTech’s long-running print column in which industry experts answer common quality and regulatory questions from the industry. Have a question you would like answered? Send it to PTProjects@mmhgroup.com, and it may appear in a future episode or print column.

Why do pharmaceutical companies continue to receive regulatory observations regarding out-of-specification (OOS) procedures despite clear guidance from regulators?^1,2 The issue is rarely the regulatory process itself, but rather how companies apply and interpret it, according to Susan J. Schniepp, distinguished fellow at Nelson Labs, and Siegfried Schmitt, PhD, vice president, Technical at Parexel.

A significant challenge is the creation of overly restrictive internal procedures that cause problems with the procedure, such as requiring the original analyst to complete an investigation before taking leave, which results in a delay in the investigation. To move past these bottlenecks, the experts advocate for robust trending instead of treating OOS results as isolated events. Trending helps identify recurring issues with specific methods, personnel, or aging equipment, which is often neglected in budget cycles.

Furthermore, trending should serve as a key performance indicator focused on the quality and timeliness of the investigation, rather than an unrealistic goal of having zero OOS results. Schniepp and Schmitt emphasize that investigations must extend beyond the laboratory. They recommend process mapping the entire chain of events—including sampling, which is frequently performed by manufacturing personnel without sufficient lab or quality assurance department oversight. By performing a risk assessment on the entire process, companies can predict where human error is likely to occur, allowing for faster root cause identification.

For manufacturing environments involving contract partners, it is vital that all parties operate under the same OOS procedure to ensure the integrity of the investigation. The discussion concludes that a robust OOS program requires holistic training for all staff on the entire procedure, combined with electronic systems that provide immediate access to necessary data. By focusing on process transparency and trending, manufacturers can move from reactive troubleshooting to a defensible, controlled operation.

Watch the video above to find out how Schniepp and Schmitt answer the question, “We have routinely gotten regulatory observations on our out-of-specification (OOS) procedure? What can we do to make that procedure more robust?”

References

1. FDA. Investigating Out-of- Specification (OOS) Test Results for Pharmaceutical Production. Guidance for Industry. May 2022. https://www.fda.gov/media/158416/download
2. MHRA. Out of Specification Guidance. March 2, 2018. https://mhrainspectorate.blog.gov.uk/2018/03/02/out-of-specification-guidance/

About the Experts

Susan J. Schniepp is distinguished fellow at Nelson Labs and a member of PharmTech’s Editorial Advisory Board.

Siegfried Schmitt, PhD, is vice president, Technical at Parexel and a member of PharmTech’s Editorial Advisory Board.