The Many Ways How Digitalization Is Improving Sterility Testing

Do you know what percentage of citations in post-inspection, FDA Warning Letters relate to documentation issues and written procedures? The answer is a staggering 40%. Most manufacturing facilities still base their QC data management on a combination of paper documents, spreadsheets, and digital tools for individual instruments, which increases the likelihood of errors in their documentation. Manual documentation can be incomplete or contradictory, data entered into the wrong field or saved in the wrong place—the list of potential errors is long. In response to the growing stream of data integrity issues, the FDA published its industry guidance Data Integrity and Compliance With Drug CGMP in 2018, in which it requires data to be “attributable, legible, contemporaneously recorded, original or true copy, and accurate (ALCOA).” These original principles have since been updated to ALCOA+ with its four additions: completeness, consistency, endurance, and accessibility of the data. 

From manual to digital data management

It is important to stress that data integrity regulations apply to any form of data management, whether digital or paper-based. The ALCOA+ principles may leave some room for interpretation, but regulators will only become stricter as digitalization in the industry progresses. While performing a sterility test in an isolator, an operator cannot take notes because the hands are in the gloves. Consequently, documentation is performed sometime later, based on the operator’s memory. Uncertainty over whether this practice is and will be considered contemporaneous is putting QC managers in compliance limbo.

However, most data integrity and traceability shortcomings of manual documentation can be addressed by a supportive digital solution. After translation of a QC test’s existing SOPs into digital workflow steps, such a system can guide the operator through the entire test, step by step. Communicating both ways, it can give commands to the operator who, in turn, must give feedback when a step has been concluded. It can also capture information in real-time from instruments and, via their matrix codes, from consumables and samples. This was the basic idea behind developing our recently launched 21 CFR Part 11 compliant M-Trace^® System for full traceability in compendial sterility testing by membrane filtration.

Standalone and customized setups

At the center of the pre-validated standalone setup is a computer that runs the M-Trace® software and that is connected wirelessly to a handheld device that resembles a smartphone and by data cable to a Steritest^® Symbio Pump. In the computer’s software, user rights are set up and the SOPs are converted into fully customizable digital records that define the workflow steps and determine the data to be captured at each point. The handheld device scans the details of consumables, samples, and if necessary any labeled container with a QR code, and it can even scan through the glass pane of an isolator when attached to its outside. All relevant pump data is captured and stored in real-time, including pump speed, pressure, and filtration times. Operator feedback is given either by pressing a button on the pump or by voice, using a headset that is wirelessly connected to the pump. In a customized setup, the M-Trace® software can be integrated into a manufacturer’s existing digital QC environment, allowing the reports it generates to be transferred to a LIMS, without the need to connect to outside servers.

Lower risk of handling errors

Reducing the risk of data management errors and achieving full traceability, however, do not necessarily lower the risk of handling errors during testing. It has been estimated that human errors account for between 30 and 80 percent of false results in labs. Fortunately, digitalization can also reduce such errors, thereby improving productivity. The M-TraceTM software bypasses error-prone and time-consuming paper forms and Excel sheets requiring second-person verification. It prompts operators to strictly follow the digital SOPs, which helps train new personnel. Typical mistakes and mix-ups can be avoided. If, for example, the mobile device scans in the wrong consumable, one that has expired or that is not available in sufficient amounts, the operator is promptly alerted. This ensures that everything to go into the isolator is readily at hand before starting. The system’s software-based guidance continues through the testing and examination stages to data review and approval. All data and all reports are digitally available at any time, speeding up batch release, allowing long-term trend analyses, and ensuring a full audit trail to facilitate any OOS investigation that might become necessary.

It is no coincidence that many of the advantages resemble those of data management solutions for environmental monitoring (see earlier article). All areas of microbial QC are seeing improvements brought about by digitalization.

Find out about the new M-Trace® digital companion for software-guided compendial sterility testing. www.SigmaAldrich.com/M-Trace

Author Details 

Michel van Musschenbroek- BioMonitoring Commercial Applications Field Support, MilliporeSigma, Burlington, MA, USA, An affiliate of Merck, KGaA Darmstadt, Germany; Nicolas Lelievre, PhD- BioMonitoring Regional Application & Commercial Tactics Manager, Millipore SAS, Molsheim, France, An affiliate of Merck, KGaA Darmstadt, Germany

Publication Details 

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