Introduction
In pharmaceutical manufacturing, utility gases like compressed air must meet stringent quality standards to ensure product safety and regulatory compliance. Yet many facilities, especially new or expanding ones, lack fully developed qualification programs for these critical systems. This article presents a real-world case study involving a pharmaceutical company in Bethlehem, PA, where we implemented a comprehensive utility validation program, investigated and resolved hydrocarbon contamination, and supported the qualification of associated systems including purified water, cleaning validation, and environmental monitoring, through to routine monitoring support.
PART 2 – Purified Water System Qualification
Title:
Purity Under Pressure: Qualifying a New Purified Water System in a new Facility
Intro:
Purified water (PW) is one of the most heavily used utilities in pharmaceutical manufacturing, directly affecting product quality, cleaning, and final formulations. In a new solid oral dosage facility in Bethlehem, PA, we implemented a full qualification program for a newly installed PW system, navigating startup challenges, microbial spikes in feed from the city, and regulatory requirements to deliver a system fit for GMP use.
Understanding the System and Requirements
The PW system included:
- Pretreatment (softener, carbon bed)
- Reverse Osmosis (RO)
- UV disinfection
- Storage and distribution loop with multiple points of use
We aligned the qualification approach with USP <1231>, USP <643>, and EP 2.2.44, focusing on:
- TOC (Total Organic Carbon) – organic contamination
- Conductivity – ionic purity
- Heterotrophic Plate Count (HPC) – microbiological control
- Total Coliforms – microbiological control
Three-Phase Qualification Approach
We adopted a three-phase strategy widely recognized in the industry:
- Phase I (Shakedown): Daily monitoring of all critical parameters at feed, post-UV, post-filtration, and all points of use (POU) to establish system capability.
- Phase II (Stability): Weekly sampling after operational controls were confirmed.
- Phase III (Routine): Extended monitoring at operational frequency to demonstrate ongoing control and suitability for GMP use.
Early Findings and Troubleshooting
Initial testing revealed:
- Slightly elevated HPC counts at distal POUs
- High variability in TOC near startup due to organic leaching from new piping
We worked with engineering and maintenance to:
- Flush POUs regularly
- Replace UV lamp and verify dose output
- Implement hot water sanitization sequence
By the end of Phase I, all parameters met specification and trended downward consistently.
Establishing Long-Term Monitoring
A sampling plan was created with:
- Defined alert and action limits for TOC, conductivity, and HPC
- Routine weekly verification during early production
- Annual requalification plan
Outcome
After two months of progressive qualification:
- All POUs demonstrated consistent compliance with pharmacopeial limits
- Trend data was documented to support product filings
- PW system entered routine operation with QA oversight
- Monitoring proceeded with no issue on weekly POU samples, and monthly pre-treatment points.
Stay tuned for Part 3: We’ll explore the cleaning validation program developed for oral solid dose equipment, using TOC as a key analyte for worst-case verification.
