Microbiology - Articles and news items

Hot topics in rapid methods: revisions to validation guidance and real-time environmental monitoring

Issue 6 2012 / 18 December 2012 / Michael J. Miller, President, Microbiology Consultants, LLC

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. (more…)

Rapid micro methods and the next generation in ATP bioluminescence

Issue 5 2012 / 25 October 2012 / Michael J. Miller, President, Microbiology Consultants, LLC and Noe Miyashita, Researcher, Hitachi Plant Technologies, Ltd

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. (more…)

Microbiology Series 2012 – Part 1

Supplements / 24 September 2012 / Dr. Michael J. Miller

We are pleased to present the first three articles in our Microbiology series on Rapid Microbiological Methods written by Dr. Michael J. Miller:

• New year, old challenges!
  A discussion of 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
  A review of a relatively new process that the European Medicines Agency (EMA) launched that allows for the review and approval of RMM validation strategies before testing is initiated.
• Rapid sterility testing and the impact of recent changes to the US Code of Federal Regulations
  Recent changes in regulatory policy make it clear that RMMs for finished product sterility testing have a place in our industry, and it is the FDA that is leading the motivation for change. (more…)

Opportunities for rapid methods discussions: where the experts are meeting!

Issue 4 2012 / 3 September 2012 / Michael J. Miller, President, Microbiology Consultants, LLC

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 experiences 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. (more…)

Charles River Laboratories interviewed by European Pharmaceutical Review at analytica 2012

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.

New year, old challenges!

Issue 1 2012 / 28 February 2012 / Michael J. Miller, President, Microbiology Consultants, LLC

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. (more…)

Working independently or as part of a team: Which works best?

Issue 1 2012 / 28 February 2012 / John Gappa, Microbiologist, GlaxoSmithKline

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. (more…)

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

Issue 6 2011 / 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…)