When it comes to assuring the quality of raw materials in pharmaceutical water production, real-time testing (RTT) [or real-time release testing (RTRT)] is becoming more and more commonplace. Data integrity, data transfer, data security, and data management are all parts of a successful RTT strategy.
With the adoption of electronic records in the digital age, 21 CFR Part 11 and ALCOA+ provide guidelines for maintaining data transfer and data integrity.
21 CFR Part 11 enforces controls and requirements related to the following:
- Data security
- Data retrieval
- Audit trails
- Operational, authority, and device controls
- Electronic signatures
ALCOA+ principles set the guiding principles for data integrity in a cGMP environment by requiring that data is attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring and available.
Equipment and instrumentation at a pharmaceutical site typically transfer data in a tiered manner.
Field Level: Data is generated from equipment and instrumentation currently in use.
Control Level: Data is transferred to data processors such as a programmable logic controller (PLC) or proportional integral derivative controller (PID). At these controllers, data is continuously monitored and trended for process control purposes.
Supervisory Level: Data is transferred to a supervisory control and data acquisition (SCADA) system or historian. This supervisory level compiles data and functions as a control, alarm, and distribution center.
Management Level: Data is then transferred to a manufacturing execution system (MES) with the ability to track raw materials and finished products, and to use the output data across multiple platforms to improve process efficiencies.
Enterprise Level: An enterprise resource planning (ERP) system optimizes business efficiencies by monitoring scheduling, inventory, and order processing. Once sign-offs are completed for compliance requirements, reports are entered into an electronic batch record (EBR) for data storage purposes.
When transferring data between departments — for instance, from the quality laboratory to the production floor — security is paramount. Utilizing an encrypted platform with password-protected user permissions is fundamental for the collection, review, transfer, and verification of data. To learn about Sievers software solution to data security, visit DataShare Elite.
Transitioning to RTT provides the ability to monitor and control processes while also releasing water for TOC and conductivity simultaneously. For reporting purposes, an RTT report should start with a defined collection period, one which aligns with the production schedule to ensure the data isolated from the online instrument of record is indicative of the timeframe in which water entered a new production run. When considering the frequency of measurements, ASTM E2656 – Standard Practice for Real-time Release Testing of Pharmaceutical Water for the Total Organic Carbon Attribute – recommends considering the instrument delay time, response time, cycle time, update rate, rate of change of total organic carbon (TOC) concentrations, rate of water consumption, detection, probability of exceeding TOC specification levels, and comparative costs of out-of-specification (OOS) product. The purpose of assessing these variables is to build confidence in the ability of the instrument to detect and measure TOC concentration variations.
With RTT, the data landscape changes by decentralizing quality assays; in other words, by moving TOC and conductivity to the production floor. This transition must be accounted for, in order to maintain 21 CFR Part 11 and ALCOA+ compliance. Click here to learn more about RTT.