WATER NEEDS IN PHARMA QUALITY CONTROL

Importance of the topic

Water is essential in pharmaceutical R&D, manufacturing, cleaning, and QC processes
It serves as ingredient, reagent, solvent, and product
Contaminants in water pose chemical, particulate and microbiological hazards affecting drug quality and patient safety
Strict control of water purity is critical to meet regulatory standards and ensure reliable QC results

Objectives and overview of the article

This whitepaper examines the multifaceted role of water in drug production and QC laboratories
It outlines regulatory requirements (FDA, EMA, SFDA, PMDA), water quality grades (USP, EP, ISO) and industry standards
Key questions addressed include ensuring on-demand water compliance, microbial control, WFI production and troubleshooting QC failures

Methodology and instrumentation used

Water purification systems validated under GxP guidelines via DQ, IQ, OQ and PQ
Microbial control through system design features, routine sanitization and digital traceability
Production of WFI from potable feedwater with distillation or membrane processes
Performance qualification in three phases with intensive chemical and microbiological monitoring
Analytical methods employed:

• Chromatography: HPLC, UPLC, LC/MS/MS for identity, purity and potency testing
• Enzyme assays: ELISA for specific contaminant detection
• Protein analysis: SDS-PAGE
• Microbiological testing: endotoxin assays, total viable counts, microbial identification
• TOC, pH, conductivity and UV spectroscopy for routine water quality checks

Instrumentation for water quality monitoring:

• Online TOC analyzers
• Conductivity and resistivity meters with alarm settings
• Automated sampling and electronic signature audit trails

Main results and discussion

Effective control of water quality prevents QC anomalies and product recalls
Water grade requirements vary by API process stage: initial/intermediate steps may tolerate lower grades, final rinse and formulation require USP/EP purified water or WFI
Validated purification systems deliver consistent water quality on demand, reducing human error
Three-phase PQ ensures system robustness throughout seasons and operational demands
Digital monitoring and plug&play compliance streamline audit readiness and regulatory reporting

Benefits and practical applications of the method

• Minimizes risk of contaminated water affecting drug safety and efficacy
• Ensures regulatory compliance across global authorities
• Reduces downtime and manual error through automated validation and monitoring
• Supports accurate analytical and microbiological QC testing
• Facilitates rapid investigation and root cause analysis in QC failures

Future trends and potential applications

• Integration of real-time digital water quality monitoring with LIMS and ERP systems
• Advanced sensor technologies and AI for predictive maintenance of purification systems
• Continuous inline monitoring of microbial and chemical parameters
• Improved environmental footprint through efficient system design and water reuse
• Standardization of global water quality protocols for harmonized compliance

Conclusion

Stringent water quality management is fundamental to pharmaceutical production and QC laboratories
Validated purification systems and comprehensive monitoring strategies build confidence in QC results
Proactive adoption of digital tools and robust validation ensures ongoing compliance, operational efficiency and patient safety

References

1. WHO Quality Assurance of Pharmaceuticals, Volume 2 May 2008
2. FDA Inspection Guide, Pharmaceutical Quality Control Labs 2018
3. IVTN Network API Pharmaceutical Water Systems Part I, 2020