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Microbiology - Articles and news items
The Encyclopedia of Rapid Microbiological Methods: The new fourth volume discusses technologies, regulatory acceptance and validation case studies
This is the second paper in our continuing series on Rapid Microbiological Methods (RMM) that will appear in European Pharmaceutical Review during 2013. As the editor for the Encyclopedia of Rapid Microbiological Methods, I provide a summary of the latest volume, which was published earlier this year. New case studies, regulatory guidance and novel technologies are highlighted, and encourage our industry to adopt new ways of performing microbiology assays across a wide range of applications.
For sterile as well as nonsterile pharmaceutical products, manufacturers must eliminate or minimise potential risks to patients as well as product quality. While many contributing factors may affect the quality of a medicine or its ingredients, microbial contamination control and proper sterilisation methods are critical considerations for the manufacturer throughout the product’s life cycle.
Hot topics in rapid methods: revisions to validation guidance and real-time environmental monitoring
This is the sixth and final paper in our continuing series on Rapid Microbiological Methods (RMM) that have appeared in European Pharmaceutical Review during 2012. As many of you already know, I am keen on staying on top of recent developments in the world of rapid methods, and have used my own blog (http://blog.rapidmicromethods.com) to communicate technology advances and changes to regulatory and validation practices and expectations. In my final article of the year, I am providing an overview of two very interesting topics that have sparked additional discussions within the professional community: the proposed changes to USP’s informational chapter on the validation of alternative microbiological methods and real-time environmental monitoring.
Revision to USP Chapter <1223>: 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 RMMs.
Because many RMM technologies consist of a combination of instrumentation, software, consumables and reagents, in addition to specific detection, quantitative or identification methodologies, it is important to develop a comprehensive and holistic approach to the validation process to ensure that the entire RMM system is suitable for its intended use.
This is the fifth paper in our continuing series on Rapid Microbiological Methods (RMM) that will appear in European Pharmaceutical Review during 2012. As many of you know, I am always on the lookout for the next generation of rapid microbiological method (RMM) technologies and solutions. In this article, I have invited Noe Miyashita, a researcher from Hitachi Plant Technologies, to describe a novel ATP bioluminescence technology platform that she and her colleagues are currently working on. But in order to frame this discussion, it is appropriate to provide some background material on the fundamental basics of ATP bioluminescent methods.
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. Specifically, in the presence of the substrate luciferin, the enzyme luciferase will use the energy from ATP to oxidise luciferin and release photons (light at a wavelength of 562 nanometres). The photons can then be detected and measured by a luminometer equipped with a photomultiplier tube. Figure 1 provides an illustration of this chemical reaction.
Supplements / 24 September 2012 / Dr. Michael J. Miller
How the acceptance of rapid microbiological methods (RMMs) continues to be hampered by misconceptions, misunderstandings and myths.
Rapid micro methods and EMA’s post approval change management protocol.
Rapid sterility testing and the impact of recent changes to the US Code of Federal Regulations.
This is the fourth paper in our continuing series on Rapid Microbiological Methods (RMM) that will appear in European Pharmaceutical Review during 2012. Over the past few years, a number of professional meetings have focused on strategies and case studies for the validation and application of rapid microbiological methods (RMM). If you were able to attend one of these meetings, you probably found it encouraging and worthwhile listening to and speaking with end-users, regulators and vendors of the technologies. This year and next are no exception; scheduled conferences and training sessions within Europe and the US will provide the industry with a comprehensive overview and guidance on how to successfully implement RMMs. To give you a feel for what’s in store, this edition of our RMM series will highlight upcoming PDA and ECA RMM sessions. In addition, the last section will provide more information about the overall October 2012 PDA Global Conference on Pharmaceutical Microbiology, of which a number of RMM presentations will be delivered.
European Compliance Academy (ECA) Annual RMM Conference (December 2012):
This two-day conference offers you a unique opportunity to evaluate the new developments in RMM systems, to extend the current experi – ences in validation, as well as implementation of these systems within the pharmaceutical industry. Attendees will also learn about the expectations of the regulatory authorities and new developments with regard to regulatory requirements.
Videos / 18 April 2012 / Freddy White, European Pharmaceutical Review
Yvonne Boss, European In-Vitro Specialist Sales Manager at Charles River Laboratories speaks to Freddy White, Director of the European Pharmaceutical Review at analytica 2012.
This is the first of many articles in our continuing series on Rapid Microbiological Methods that will appear in European Pharmaceutical Review during 2012. For the past two years, I have enjoyed sharing with you a broad range of topics associated with the validation and implementation of rapid microbiological methods (RMMs), including:
- A review of the history of conventional micro – biology and the benefits of using RMMs
- Validation strategies
- Perspectives from the regulatory authori – ties, including FDA and EMA
- Overviews of currently available tech – nologies, including those based on the growth of microorganisms, detection of cellular targets, optical spectroscopy, nucleic acid amplification and gene sequencing, viability staining and laser excitation, as well as micro-electro-mechanical systems, or MEMS.
In addition to my articles, numerous companies have published their success stories of RMM selection, validation and implementation, for a variety of applications including, but not limited to, sterility testing, bioburden analyses, water testing, environmental monitoring and the detection of Mycoplasma and other micro – organisms.
When I sat down to write this article, my immediate thought was about work styles. Is it better to work independently or in teams? Wouldn’t it be great to hear from someone on the ‘floor’ who has worked both in the lab and in the production environment? Work styles: independent or team based. Which one is better?
For 20 years, I have worked for several organisations and the involvement for both work styles have varied. Initially, I was an independent analyst and over the years, my work style has progressed to a team based organisation. I am presenting an article to state that after evaluating my roles in research development for parenterals and clinical manufacturing, aseptic manufacturing and biopharmaceuticals; the team based approach is the better of the two styles with regards to microbiology and the production environment.
At the start of my career, I learned the basics of pharmaceutical microbiology from five individuals. Each of us had core responsibilities and there were some group functions that we worked in a team to complete but most analyses were independent as a result of the technical level / experience of the analysts.
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.
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.
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.
ABB Analytical Measurement Analytik Jena AG Aptalis Pharmaceutical Technologies ASM - Aerosl-Service AG Azbil BioVigilant, Inc. B&W Tek, Inc. bioMérieux BioTrends – Archilex SA BMG LABTECH GmbH Bruker Daltonik GmbH CAMO Software AS Catalent Pharma Solutions Chemspec Europe Ltd CI Precision Dow Chemical Company Ltd EUROGENTEC FOSS NIRSystems, Inc. GE Analytical Instruments Gerresheimer Group HAMAMATSU PHOTONICS EUROPE I Holland Limited IDBS IONIMED Analytik GmbH LI-COR Biosciences Lonza Natoli Engineering Company, Inc. Pall Life Sciences PANalytical B.V. Patheon Inc PhyNexus, Inc. ReAgent Roche Sirius Analytical Instruments Ltd Vala Sciences Veltek Associates Inc.