Nicholas Machado- Global Product Manager Services, Rapid & Automation, Millipore SAS, Molsheim, France, An affiliate of Merck KGaA, Darmstadt, Germany; Anne Weeks- Senior Field Marketing Manager BioMonitoring, MilliporeSigma, Burlington, MA, An affiliate of Merck KGaA, Darmstadt, Germany
As the pharmaceutical industry enters a new transformational phase, there is immense potential for automation and digitalization to improve workflows and boost productivity. Innovative solutions are being implemented in all areas of the industry, from research and product development to manufacturing and quality control. In a tightly regulated industry like pharma, eliminating causes of handling errors and ensuring full QC compliance are particularly important, as this minimizes the likelihood of disruptive and costly root cause analyses and batches having to be discarded, or worse, interventions by regulatory authorities. For sterility testing by membrane filtration, it is now becoming clearer what the future holds in store.
The challenges and limitations
The pharmaceutical industry performs sterility tests on a wide spectrum of products in matrices with different physical and chemical properties. Sampling inevitably builds on the product’s final packaging, of which many different varieties exist. Every product requires a specific standard operating procedure (SOP), including the appropriate volumes of compatible solutions, consumables to use and filtration settings, all of which have to be documented.
Once set up, SOPs must be followed to avoid errors that can lead to false positive or false negative results. Minor deviations in staff members’ practices, resulting from different interpretations of the SOP, can impact a test result, and although manufacturers tend to entrust skilled and experienced staff with the complexity of sterility testing, complacency can set in over time. Since it is impossible to log each step while simultaneously performing a sterility test in an isolator or laminar flow hood, documentation is usually performed manually at the desk afterwards, in writing or at the computer. This creates a potential source of discrepancies between what was done and what was protocolled, which would breach regulations and complicate a root cause analysis should one become necessary.
Strategy 1: Guided handling according to SOP
We have identified two strategies to further improve sterility testing. The first is software-guided SOP. The software will prompt step-by-step instructions and record user feedback after a step has been successfully completed. All actions of the test can be programmed to guide operators through specific routines such as sampling, filtration, inspection of consumables prior to use. It can also help to prepare a test before getting started by requiring the operator to scan in the needed consumables, ensuring nothing is forgotten. The software gives an alert if an expiration date has passed or when a handling error is about to be made. This reduces mistakes and helps to avoid any missed handling steps. In effect, this approach specifies a sterility testing workflow in detail and oversees what is being done.Of course, SOPs differ depending on the sample, requiring every SOP be entered into the software to program a workflow. This compels a lab to define its SOP unambiguously, leaving no room for interpretation. The bottom line is that this approach makes compliant sterility testing less complex for lab personnel. Training new operators becomes easier, lowering the level of experience and expertise needed; a huge advantage in times when skilled staff is difficult to attract and maintain.
Strategy 2: Automated digital data management
The second strategy is to improve data management for greater reliability and confidence in regulatory compliance. Data integrity based on the ALCOA set of principles, originally introduced by the FDA, requires that data be attributable, legible, contemporaneous, original, and accurate, with the extended ALCOA+ additionally needing data to be complete, consistent, enduring and readily available. The best way to meet these requirements is for a 21 CFR Part 11 compliant software to automatically record all handling steps immediately after the operator performs and confirms them, in addition to comprehensive data from the scanned-in consumables and the workflow as set up in the software.
The resulting full traceability and compliance makes out-of-specification investigations easier. Integration into the facility’s IT environment can leverage efficiency gains and save valuable time on documentation, reviewing of records and batch releases. Error-prone documentation on paper or entries into spreadsheets after a test become unnecessary.
Combining both strategies into a solution
We implemented the two strategies in full when we developed our M-Trace™ software, which enables semi-automated control of the Steritest® Symbio Pump for sterility testing. It allows SOPs to be flexibly defined. In the pre-validated stand-alone setup, the software runs on a computer, but communication during testing is via headset and voice or, alternatively, the pump’s display. A mobile device, similar to a smartphone, scans data matrix codes to capture information of consumables. In an advanced setup, the software can be integrated into a customer’s existing digital QC environment, allowing reports to be generated and transferred to a LIMS.
Find out about the M-Trace™ digital companion and our installation, validation and integration services to support implementation.
www.SigmaAldrich.com/M-Trace
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