Monday 29 April 2024

Raising the bar with sterility test compliance: Merck’s M-Trace® System

Maintaining compliance for the sterility test, demonstrating the validated state, enabling testing consistency, and showing traceability of consumables – each an important component of laboratory data integrity – has been made easier through the introduction of Merck’s M-Trace® system. This article looks at the importance of sterility test compliance and how M-Trace® can deliver the solution.

By Tim Sandle

The test for sterility


The pharmacopeial test for sterility is one of the most important laboratory tests and a regulatory requirement for aseptically filled pharmaceutical products. A test recording a ‘pass’ result, together with evidence of sterility assurance during manufacturing, provides evidence of the quality of the manufactured product.


The most common form of the test is the membrane filtration method, where the presence or absence of microorganisms is assessed through an examination of turbidity, following incubation, of microbiological culture media.


Maintaining the validated state


The criticality of the test places it under regular audit scrutiny, from the validation of the test to its routine performance. Sterility test validation is performed to develop a test method through which it can be demonstrated that the product does not have a microstatic or microbicidal effect.


To show that the test has been conducted effectively and following the initial validation, a series of parameters need to be controlled (such as the use of the correct membrane filter; the speed at which the product is passed through the membrane filter; and the number of rinses required to remove any potentially antimicrobial product residues). These parameters often vary between products and include:


  • The test kit to be used
  • The rinse solution to be used
  • If a reconstitution fluid is required
  • The pump speed
  • The number and volume of rinses required.


Many of these parameters need to be submitted as part of the regulatory filing for new products. It is also important that the validated conditions are accurately captured in the test procedure and replicated by each analyst who performs the test.




It is also important to carefully record the culture media used (typically soya-bean casein digest and fluid thioglycolate media). These media need to undergo quality control testing and release, before being used in the sterility test. The release process includes growth promotion testing (using pharmacopeia strains and isolates from the facility’s own manufacturing environment) and a ‘sterility test’ (incubating some of the test bottles to show the absence of contamination). Use of the incorrect culture medium will lead to test invalidation.


In addition, the consumables used in the sterility test also need to be captured, including the test kit and rinse fluids. Different test kits and rinse fluids may be required for different product families, and knowing which consumables were used is essential should a sterility test failure investigation be required.


Data integrity


The adherence to the validated state and traceability requirements must conform to data integrity expectations. This is especially critical for a final product release test like the sterility test. A useful acronym when considering data integrity, and one that serves as an appropriate summary point, is ALCOA. Here: data must be attributable, legible (permanent), contemporaneous, original and accurate. This means:

  • Attributable: The identity of the person completing a record should be unambiguous.
  • Legible (permanent): It should not be possible to modify or recreate data without an audit trail that preserves the original record. For paper records, what has been written needs to be understandable.
  • Contemporaneous: System design impacts upon contemporaneous record keeping. For instance, the availability of records in the right place at the right time removes the need for staff to remember things to write down or entering into a computer later on.
  • Original: Original records must preserve data accuracy, completeness, content and meaning.
  • Accurate: Automated data capture, with the required controls, provides greater control over the accuracy of a record.

From the above, where a computerised system is used, the system must:


  •  Permit access by authorised personnel only.
  •  Be password controlled, with different access levels.
  •  Allow for the creation of backup copies.
  •  Operate an accurate and secure audit trail.


M-Trace® Solution


To help address the above best practice requirements, Merck has developed a means of ensuring that sterility tests are conducted as designed and validated (through the use of electronic standard operating procedures) and that all consumables are captured and connected with the relevant sterility test. This is through M-Trace®, a system that ensures the sterility test achieves an improved state of compliance.


The use of the electronic procedure also ensures that operational steps are not missed or performed out of order and that any ambiguity or different interpretation between analysts is minimised.


M-Trace® Software


The first part of the system is the M-Trace® Software. This enables semi-automated control of the Merck Steritest® Symbio Pump (used for the sterility test using the membrane filtration method). The analyst can view the software and control the operational steps via a headset and voice commands or directly from the Symbio Pump display. This streamlines the workflow and, through the avoidance of errors or delays to verify the required steps, it can boost productivity.


Automating the workflow: M-Trace® Touch Mobile Computer


The second part of the system is a mobile device, which resembles a smartphone, used to scan and digitally capture the data matrix codes of consumables. With this, Merck has developed a digital companion called the M-Trace® Touch Mobile Computer.


Capturing test consumables accurately is not only important; this is an area that can be prone to error within a busy laboratory, especially within the sterility test suite here personnel will be wearing cleanroom-style gowns and gloves. The M-Trace® Touch Mobile Computer enables consumable data to be captured accurately and the automation element ensures that no consumables are missed, and that traceability is achieved through automation. Where scanning is undertaken within the sterility test facility, the M-Trace® Touch Mobile Computer is positioned outside of the Grade A zone (outside of an isolator or unidirectional airflow device), using the M-Trace® Mobile Computer Mount, enabling the analyst to perform the scanning hands-free.


Laboratory compliance: M-Trace® Electronic Test Record Software


When the user is within range of the M-Trace® All-in-One PC (MTRACEPC1) the data is transmitted to the electronic test record. Hence, the M-Trace® Mobile App connects to M-Trace® Electronic Test Record Software. This enables the analyst performing the sterility test to digitally capture records of consumables used in the sterility test together with test results.


In addition, the digital information can be integrated into a Laboratory Information Management System (LIMS), here a laboratory supervisor or manager can review the test parameters and consumables prior to releasing the result.


Compliant solution


The M-Trace® system aids the laboratory in improving compliance by reducing the potential for error (in terms of testing and data capture) and provides an electronic repository to enable the accurate release of test results and a digital archive should test problems or failures be encountered, as well as providing a means for an auditor to examine historical test results.


The life science business of Merck operates as MilliporeSigma in the U.S. and Canada.

Dr. Tim Sandle, Pharmaceutical Microbiology Resources (

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