The real-time release of pharmaceutical water enables TOC testing to move from the laboratory to the production floor, improving quality and reducing costs in the process.
Validation Documentation and services
- Method validation
- Method comparability and transfer
- Measurement system equivalency
- Historical data collection and review
- Point-of-use quality verification
Consulting (Defining future state)
- Current state assessment
- Critical point of use screening
- Failure Mode Effects Analysis (FMEA) and risk ranking
- Future state mapping
- Sample consolidation plan
- Implementation guidance
GE Analytical Instruments, part of GE Power & Water, manufactures highly sensitive and robust scientific instruments, and is the leading provider of total organic carbon (TOC) analysers to the pharmaceutical industry. Companies worldwide rely on its Sievers TOC analysers for monitoring and releasing pharmaceutical waters for USP, EP, and JP compliance, cleaning validation and quality initiatives such as process analytical technology (PAT). The company has established market leadership in using TOC for cleaning validation, and now offers a new science- and risk-based program for implementing real-time release (RTR) of pharmaceutical water.
Production benefits
TOC is a critical water quality attribute. Historically, the pharmaceutical industry has measured TOC in the laboratory using grab samples. This process is more inefficient and less reliable than using online TOC analysers critically located within the water distribution system. Laboratory-based quality systems rely on analysts to take samples manually from the water system and bring them to the laboratory for testing. This process is both labour-intensive and time-consuming, causing delays in analysis results and water release.
Laboratory-based testing is also very costly. Based on GE Analytical Instruments’ estimates, a typical pharmaceutical company analyses more than 2,500 routine TOC samples annually. Depending on sample loads, each sample costs $55 to $111, most of which is for manual sampling. By transitioning from the laboratory to online TOC analysis, manufacturers can reduce sampling costs by up to 90%.
Regulatory support
The pharmaceutical industry has been slow to adopt continuous improvement strategies for various reasons, including the regulatory uncertainty of applying guidances such as the FDA’s 2004 PAT document (called Guidance for Industry: PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance). However, because both industry and regulators are realising that continuous in-process measurements provide inherent quality improvements and cost advantages, pharmaceutical quality systems are moving to real-time analyses and process control. The PAT document provides a framework for using process analytical tools for compliance with current good manufacturing practices (cGMPs). It defines RTR as "the ability to evaluate and ensure the acceptable quality of in-process and/or final product based on process data".
Streamlining RTR
GE Analytical Instruments has developed a program called Implementing On-Line TOC for Real-Time Water Release, part of GE’s Quality System Optimization (QSO) service offering. For short, the RTR program is called QSO/RTR. It provides a framework for transitioning TOC testing from the laboratory to the production floor. Historically, RTR programs have been reputed to be complex, often taking years to implement. GE’s QSO/RTR is designed to be implemented in six months. The program incorporates lean manufacturing and Six Sigma best practices, aligned with cGMPs and regulatory guidance. QSO/ RTR provides a practical roadmap on how to evaluate variability and identify opportunities for improvement in TOC sample analysis processes. Table 1 shows some of the main components of QSO/RTR.
Before embarking on an RTR project, it is critical that companies assemble a team of decision-makers in areas such as quality, operations, facilities and engineering. During the ‘Defining Future State’ phase shown in Table 1 (above), a GE facilitator will work with this cross-functional team through several critical process design decisions using an analysis of the water system’s current state, risk assessments and future state mapping to arrive at an optimised solution for RTR.