Milliflex® Rapid Microbiology Detection and Enumeration System for Bioburden Testing

An Automated System for Rapid, Accurate Detection and Enumeration of Microorganisms

The Milliflex® Rapid Microbiology Detection and Enumeration system is an automated solution for the rapid detection, response, and resolution of microbial contamination in filterable samples throughout the manufacturing process. The system improves process control, product yield and the timely release of products. Based on Adenosine Triphosphate (ATP) bioluminescence technology, the Milliflex® Rapid system delivers faster test results than traditional microbial contamination detection methods, such as membrane filtration (MF) and pour plates. The Milliflex® Sample Prep method also ensures consistent, reliable results. The Millilfex® Rapid system can clearly distinguish between mixed microbial growth of slow growing and fast growing microorganisms, as well as variances in their size and ATP content in water samples.

Results in Hours, Not Days

With the Milliflex® Rapid system you can detect bacteria in approximately 1/4 the time of your current method. The Milliflex® Rapid system can detect and count viable microorganisms filtered onto a membrane down to 1 CFU per sample. The software displays results as familiar colony forming units (CFU) therefore providing a direct comparison with historical data obtained from traditional methods.

Three Proven Technologies

The Milliflex® Rapid system uses proven technologies including membrane filtration, ATP bioluminescence and image analysis for ease of validation.

• Membrane Filtration - Today’s standard for sample preparation. Large volumes of product can be processed and any inhibitor substances are easily rinsed away.
  
• ATP Bioluminescence - ATP (adenosine triphosphate) is a proven indicator of cell viability.
  
• Image Analysis for Enumeration of Microorganisms - The concentration of ATP required for measurement is about 200 attomoles, which is equivalent to one yeast or mold cell or approximately 100 bacterial cells, depending on their metabolic state. The sensitivity of the reagents combined with a charged coupled device (CCD) camera and image processor requires only a short incubation period to generate enough ATP for detection and enumeration.

The system captures the light signals emitted from the microorganisms on the membrane with a CCD camera. The image analysis software intensifies the bioluminescence from each cell (or micro-colony) thousands of times, and an image processor enumerates the microorganisms and displays them on a computer screen.

Automated Imaging Analysis

The technologically advanced Milliflex Rapid Image Analysis software enables analysts to test water, in-process products, raw materials and final products in a fraction of the time of traditional methods.

Access and editorial privileges are controlled by the system administrator ensuring secure data acquisition and retrieval.

The detection tower scans and develops an image of the microcolonies on the membrane.

The system counts each microcolony and stores the data for downloading, printing and retrieval. Within approximately two minutes, the sample analysis and results are displayed (Figure 2) along with the batch history and electronic image of the membrane with results displayed in familiar colony forming units (CFUs), which can also be viewed three dimensionally. Batch history allows analysts to identify trends at a glance and the electronic images confirm test results.

21 CFR Part 11 Compliance Ready

Milliflex® Rapid Microbiology Detection and Enumeration software meets the requirements of FDA Regulation 21 CFR Part 11 for Electronic Records and Electronic Signatures. The software’s powerful batch reporting feature meets the technological requirements of FDA's 21 CFR Part 11 for Electronic Signatures and Electronic Batch Reporting. The batch reporting feature includes capabilities for electronic signing, performing audit trails, and rendering data files unalterable.

Application of Bioluminescent Reagents onto Membranes

An integral component in the Milliflex® Rapid Microbiology Detection and Enumeration system, the Milliflex® Rapid AutoSpray Station applies an equal volume of two reagents across a membrane surface in order to detect living microorganisms.

Consistent, Reproducible Performance

Using a proven, pre-set automated program, the AutoSpray Station ensures reproducible results, test after test. Reagent application is achieved using a back and forth sweeping movement of the filter holder under the calibrated glass nebulizer.

Pinch valves ensure that the same volume of reagent is dispensed during each cycle. An internal compressor allows stand-alone operation, eliminating the need for additional equipment.

Streamlined Operation

In automatic spray mode, the AutoSpray Station delivers both reagents in 90 seconds at the touch of a button.
From the control panel, analysts can easily initiate an operation by selecting from a list of operations.

Easy to Clean and Maintain

The AutoSpray Station issues a warning message across the control panel when calibration, cleaning or priming are required ensuring consistent and reliable performance throughout the life of the system.

A self-cleaning unit, the AutoSpray Station is ready for re-use in five minutes. The unit should be recalibrated after every 5000 samples, or at least once a year.

Worldwide Regulatory Compliance

ATP bioluminescence technology used by the Milliflex® Rapid system is recognized as an alternative detection method by:

• FDA^1,2
  
• PDA Technical Report No. 33: Evaluation, Validation and Implementation of New Microbiological Testing Methods³

Membrane filtration is a recommended methodology in the capture of microorganisms by worldwide pharmacopoeias (US, European and Japan).

The Milliflex® Rapid system is calibrated to International light standard [LNE/NIST] and meets electrical conformity to the CE mark.

• FDA draft guidance for industry, PAT — A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance, September 2004.
  
• FDA/OPS meeting, April 13, 2004, pages 104–110, 136.
  
• PDA. May/June 2000. Technical Report No. 33: Evaluation, Validation and Implementation of New Microbiological Testing Methods. PDA Journal of Pharmaceutical Science and Technology 54(3) Supplement TR33.

Validation Support

Comprehensive protocols are available to make validation faster and easier. The validation protocol book contains ready-to-use installation, operation, and performance qualification protocols that are written to the same standards as the protocols used to validate pharmaceutical processes.

Get more from your Milliflex® system

By combining the Milliflex® products, accessories and services you can immediately streamline your microbial contamination testing workflow, leverage your quality assurance level by avoiding risks of exogenous contamination and ensure compliance to all GMP/GLP requirements.
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