Microbiology - 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…)

Inhibition of microbial growth in solid dosages at ICH stability storage conditions

Issue 4 2011 / 31 August 2011 / Linda Skowronsky, Senior Microbiologist, GlaxoSmithKline

Several intrinsic and extrinsic factors influence microbial growth. Two important factors include the presence of available moisture and a supportive temperature. The conditions described in ICH Topic Q1A (R2)1 do not allow the organisms of interest in pharmaceutical solids to grow, due to either an unfavourable temperature or humidity. For this reason, testing either microbial limits or measuring water activity as part of the stability program is considered of little value in determining microbial stability.

An optimised approach for reduced microbial testing to support stability has been proposed2,3. The rationale was given for utilising water activity measurements instead of microbial limit testing on non-aqueous solids with water activity measurements. Many regulatory authorities continue to require microbial limit data although will sometimes accept water activity data to support microbial stability. Quality by Design as described in ICH Q84 emphasises the importance of designing quality into products rather than testing in quality. Therefore, it is important to take a critical view of stability specifications and current testing. Testing typically performed during development is often generated in response to regulators inquiries that consider satisfactory microbial limit and/or water activity data will ensure microbial stability. In the case of materials of low water activity, this conclusion, however, may not accurately reflect in-use conditions. (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…)

The implementation of rapid microbiological methods

Issue 6 2010 / 16 December 2010 / Michael J. Miller, President, Microbiology Consultants, LLC

This is the sixth and final paper in a series of articles on rapid microbiological methods that have appeared in European Pharmaceutical Review during 2010. Over the past year, we have explored the world of rapid microbiological methods (RMMs), focusing on validation strategies, regulatory expectations, and the technical and quality benefits of these novel systems as compared with conventional techniques. It should be obvious by now that RMMs will significantly impact the future of microbiology within the pharmaceutical and biotech industries. But don’t just take my word for it. (more…)

Article 5: The implementation of rapid microbiological methods

Issue 5 2010 / 1 November 2010 / Michael J. Miller, President, Microbiology Consultants, LLC

This is the fifth in a series of articles on rapid microbiological methods that will appear in European Pharmaceutical Review during 2010. In my previous four articles, I have provided an overview of the benefits of rapid microbiological methods (RMMs) as compared with conventional methods, validation strategies and regulatory perspectives on the implementation of RMMs, especially from the US FDA and the European Medicines Agency. Some regulatory authorities rely on the published literature as a means of staying current with regard to new technologies that are being introduced, in addition to which companies are implementing these technologies in their manufacturing facilities. (more…)

Article 4: The implementation of rapid microbiological methods

Issue 4 2010 / 19 August 2010 / 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 2010. Believe it or not, today’s regulatory authorities encourage the use of rapid microbiological methods (RMMs), and when applicable, they have put policies in place that provide guidance on how to get a RMM approved. Because there are different regulatory perspectives on RMM implementation, a company should understand what each regulatory body expects with regard to validation, submission and implementation strategies. In my last article, I discussed a number of RMM implementation perspectives from the U.S. Food and Drug Administration (FDA). In this article, I will focus on the European Medicines Agency (EMA) and their expectations on the introduction of new RMM technologies. (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…)

Microbiological quality for non-sterile drug product for the 21st century

Industry Focus 2010, Past issues / 22 February 2010 /

For decades microbiological quality has remain dormant while the pharmaceutical industry has continued to evolve. Compendial methods and limits, while now generally harmonised throughout the world, still reflect the same methods utilised 100 years ago. Although there is more clarification around the number and types of organisms permitted in products since routes of administration are better defined, there is little change to what is considered an acceptable number or the types of organisms allowed in product. The good news is, however, in this new environment of Quality by Design (QbD) and the Process Analytical Technology Initiative1 outlined in Quality for the 21st Century, application of a Risk Based approach can provide some flexibility for microbial control. Through an enhanced understanding of the product and process gained during product development, some of the repetitive and inefficient end product testing may be replaced with real time or supportive data to confirm microbial quality. (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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