Microbiology Consultants LLC - Articles and news items

Detection of microorganisms using micro-electro-mechanical systems (MEMS)

Latest issue / 13 December 2011 / Michael J. Miller, President, Microbiology Consultants

This is the sixth and final article in our series on Rapid Microbiological Methods (RMMs) that have appeared in European Pharmaceutical Review during 2011. In our last article, we reviewed the world of nucleic acid amplification technologies, including PCR-DNA amplification, RNA-based reverse-transcriptase amplification, 16S rRNA typing and gene sequencing for the detection, identification, and in some cases, the enumeration of microorganisms. In our last article of the year, we will explore one of the most exciting areas in microbiological detection and miniaturisation: Micro-Electro-Mechanical Systems, or MEMS.

Imagine, for a moment, a machine so small that the human eye cannot see it and thousands of these machines are manufactured on a single piece of silicon. Imagine a future where gravity and inertia are no longer important, but atomic forces and surface sciences dominate. This is the world of Micro-Electro-Mechanical Systems (MEMS), and the future is now.

MEMS is the integration of mechanical, electrical, fluidic and optical elements, sensors and actuators on common silicon or other solid substrate through microfabrication technology. This is one of the fastest growing segments in the diagnostics and biomedical applications area, particularly for drug discovery and delivery, DNA testing and diagnostics, biotelemetry and genomics. And now, these same technologies are being introduced into the pharmaceutical sector for the rapid detection of contaminants. Examples of MEMS that have already been developed include Lab-On-A-Chip and microfluidics devices, microarrays, biosensors and other nanotechnology platforms. (more…)

Detection of microorganisms using optical spectroscopic-based rapid method technologies

Issue 4 2011 / 31 August 2011 / Michael J. Miller, President, Microbiology Consultants, LLC

This is the fourth in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2011. Previously, we discussed a number of cellular-component rapid microbiological methods (RMMs), such as ATP bioluminescence, fatty acid analysis, MALDI and SELDI time of flight mass spectrometry, Fourier transform-infrared (FT-IR) spectrometry and technologies that rapidly detect the presence of endotoxins. In the current article, we will review a relatively new set of rapid methods that are based on optical spectroscopy. These technologies are quite exciting, as they do not rely on microbial growth for a response and the time to result can be instantaneous.

Optical spectroscopy is an analytical tool that measures the interactions between light and the material being studied. Light scattering is a phenomenon in which the propagation of light is disturbed by its interaction with particles. There are a number of light scattering principles that may be utilised in rapid method technologies; therefore, it is appropriate to quickly review some of these principles in order to understand the scientific basis for the RMMs that will be discussed later in this article. (more…)

Detection of microorganisms using cellular component-based rapid method technologies

Issue 3 2011 / 20 June 2011 / Michael J. Miller, President, Microbiology Consultants, LLC

This is the third in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2011. In my last article, I provided an overview of viability-based rapid microbiological methods (RMMs), such as flow and solid-phase cytometry. In this article, we will review some of the currently available RMMs that fall under the category of cellular-component based technologies. These RMMs rely on the analysis of cellular markers or the use of probes that are specific for microbial target sites of interest. Examples include ATP bioluminescence, the detection of endotoxin and the use of MALDI-TOF mass spectrometry for microbial identification.

ATP bioluminescence is the generation of light by a biological process, and is most recognised in the tails of the American firefly Photinus pyralis. First discovered in 1947 by William McElroy, he described the ATP bioluminescence reaction in which ATP (Adenosine Triphosphate) is enzymatically consumed to produce light. (more…)

Article 2: Direct detection of microorganisms using viability-based technologies

Issue 2 2011 / 19 April 2011 / Michael J. Miller, President, Microbiology Consultants, LLC

This is the second in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2011. In my last article, I provided an overview of growth-based rapid microbiological methods (RMMs). This was a good place to start my review of RMM technologies, as most of us continue to use conventional agar and liquid medium for the growth of micro – organisms. In the current article, I will significantly depart from growing microorganisms to the direct detection of microorganisms using viability-based technologies, which will include flow cytometry and solid phase cytometry. (more…)

Article 1 Rapid microbiological methods 2011

Issue 1 2011 / 16 February 2011 / Michael J. Miller, President, Microbiology Consultants, LLC

This is the first in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2011. Last year, I provided an overview of rapid microbiological methods (RMMs), including validation strategies, regulatory expectations, the technical and quality benefits of RMMs as compared with conventional techniques, and an overview of a variety RMM presentations and plenary sessions during the 5th Annual PDA Global Conference on Pharmaceutical Microbiology.

During the year I also provided updates on what was new and noteworthy in the world of rapid methods, through my blog on www.rapidmicromethods.com. The response to this series was so overwhelming, I was asked to repeat the series again in 2011. Of course, I couldn’t resist (actually, my response to continue to provide guidance on RMMs was quite rapid!). As there are literally dozens of different RMM technology platforms, and just as many applications that they can be used for, it was obvious that this series would need to demystify the task of matching the right rapid method with the right application. Therefore, it is necessary to review the types of systems that are currently available, and those that are in development. (more…)

Article 3: The implementation of rapid microbiological methods

Issue 3 2010, Past issues / 24 June 2010 / Michael J. Miller, Ph.D., President, Microbiology Consultants, LLC

This is the third in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2010. Rapid microbiological methods (RMMs) have been implemented by a number of companies around the world. In some cases, it is necessary to work with regulatory authorities in order to effectively introduce a RMM in place of an existing microbiology method. This is especially true if the existing method is incorporated in a previously approved regulatory dossier, such as a New Drug Application (NDA) or Marketing Authorisation. (more…)

Article 2: The implementation of rapid microbiological methods

Issue 2 2010 / 9 May 2010 / Michael J. Miller, Ph.D., President, Microbiology Consultants, LLC

This is the second in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2010. Method validation is the process used to confirm that an analytical procedure employed for a specific test is reliable, reproducible and suitable for its intended purpose. All analytical methods need to be validated prior to their introduction into routine use and this is especially true for novel technology platforms such as rapid microbiological methods (RMMs). (more…)

Article 1: The implementation of Rapid Microbiological Methods

Issue 1 2010 / 22 February 2010 /

This is the first in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2010.

Microbiology trapped in the 19th Century

When the science of microbiology was in its early stages of development, scientists used liquid media for the cultivation of microorganisms. For those who were in need of a method to segregate individual types of organisms, the use of liquid media proved to be a significant disadvantage. This was the case for Dr Robert Koch, who, in 1881, was determined to find an alternative method for his experiments. His laboratory first used aseptically cut slices of potato as a solid culture medium, and later turned to liquid culture supplemented with gelatin, which was subsequently poured into glass plates and allowed to solidify. This technique permitted the scientists to obtain pure cultures of the bacteria that were found to be growing in the form of discreet colonies on the surface of the plates.

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Real-time environmental monitoring: PAT solutions using rapid microbiological methods

Issue 4 2009, Past issues / 30 July 2009 /

In these economic times the pharmaceutical industry has expressed a renewed interest to explore ways in which to enhance the efficiency and agility of existing and future manufacturing processes. This is also true for laboratory-based operations that support forward processing and product release decisions. One function that can greatly benefit from implementing more efficient testing platforms and realise a significant return on investment (ROI) is the QC microbiology lab. This is especially apparent when the laboratory replaces conventional growth-based microbiology procedures with more efficient rapid microbiological methods (RMMs). (more…)

Quality risk management and the economics of implementing rapid microbiological methods

Issue 2 2009, Past issues / 20 March 2009 /

Quality risk management (QRM) is an important part of science-based decision making which is essential for the quality management of pharmaceutical manufacturing₁. The ICH Q9 guideline, Quality Risk Management₂ defines QRM as a systematic process for the assessment, control, communication and review of risk to the quality of drug product across the product lifecycle. Similarly, the FDA Final Report for Pharmaceutical cGMPs for the 21st Century – A Risk-Based Approach₃, states that using a scientific framework to find ways of mitigating risk while facilitating continuous improvement and innovation in pharmaceutical manufacturing is a key public health objective, and that a new risk-based pharmaceutical quality assessment system will encourage the implementation of new technologies, such as process analytical technology (PAT), to facilitate continuous manufacturing improvements via implementation of an effective quality system.

The FDA’s PAT Guidance, which was finalised in 2004₄, describes a regulatory framework that will encourage the voluntary development and implementation of innovative approaches in pharmaceutical development, manufacturing, and quality assurance. Many new technologies are currently available that provide information on physical, chemical, and microbiological characteristics of materials to improve process understanding and to measure, control, and/or predict quality and performance. The guidance facilitates the introduction of such new technologies to improve efficiency and effectiveness of manufacturing process design and control, and quality assurance. A desired goal of the PAT framework is; therefore, to design and develop well-understood processes that will consistently ensure a predefined quality at the end of the manufacturing process, which is the foundation for the concept, that quality cannot be tested into products; it should be built-in or should be by design.
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