Validation of rapid methods continues to be an obstacle to greater adoption of these technologies. Some of the benefits of rapid methods are well articulated across industry literature, including the ability to release products much faster as well as (more…)
Issue 1 2013 / 21 February 2013 / Michael J. Miller, President, Microbiology Consultants, LLC, Silvia Fragoeiro, Ananthi Ramachandran and Paul van Empel
MSD Animal Health
This is the first paper in our continuing series on Rapid Microbiological Methods (RMM) that will appear in European Pharmaceutical Review during 2013. Flow cytometry represents one of a variety of viability-based RMM technologies that are currently available to the pharmaceutical industry. In flow cytometry, individual particles are counted as they pass through a laser beam in a very narrow flow cell.
To be used in microbiological applications, organisms are pre-labelled with a viability marker or probe, and the labelled cells are injected into the flow cell. Individual cells pass single file through a focused laser beam and are enumerated as the cells fluoresce and light scatter signals are detected. Usually, low levels of test sample volumes are utilised, such as 1 mL or less, because it takes time for this volume to pass through the narrow flow cell. The process of labelling and evaluating viable cells in these types of RMMs can be accomplished in as little as four minutes, and some systems operate automatically with little or no operator intervention or manipulations. Flow cytometry offers a relatively large range of detection operation (10-106 cells/mL) and has been demonstrated to enumerate bacteria, spirochetes, mycoplasmas, parasite cysts, yeasts and mould. (more…)
Focused on Rapid Microbiological Methods (RMMs), this one hour webinar delivers information and insight from both an end user and a supplier in order to share with you compelling reasons to consider the use of RMMs to gain a better understanding of your environment while improving your competitive advantage:
Webinars / 17 October 2012 / Rapid Micro Biosystems
** Recorded version now available to watch on-demand **
Rapid microbial testing methods in quality control continue to gain acceptance in pharmaceutical manufacturing, but most companies continue to use manual, traditional methods. The ability to uncover results in less time than traditional methods provides compelling benefits to manufacturers. These benefits (more…)
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…)
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…)
The latest innovation in rapid microbiology method (RMM) instrument technology is real-time viable detectors, like TSI’s BioTrak™ Real-Time Viable Particle Counter. This technology provides unique benefits for microbial contamination monitoring.
Issue 2 2012 / 26 April 2012 / Michael J. Miller, President, Microbiology Consultants, LLC
This is the second paper in our continuing series on Rapid Microbiological Methods that will appear in European Pharmaceutical Review during 2012. In my last article, we discussed a number of myths or misconceptions associated with the validation and implementation of rapid microbiological methods (RMMs). In fact, most RMM myths that have been circulating throughout our industry are not true or have been exaggerated to the point that many companies continue to be hesitant in exploring what RMMs have to offer.
One of the most prominent myths is that the regulators do not understand, accept or even encourage the use of rapid methods. I submit to you that the regulators want to see RMMs implemented, as their use is directly aligned with the future state of pharmaceutical manufacturing, QbD, PAT and continuous process and product improvement. Further – more, recent changes to regulatory guidance and proposed policy have made it easier to implement RMMs than ever before. In my last article, I introduced 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. A more thorough review of this process, better known as the Post Approval Change Management Protocol (PACMP), is presented herein. (more…)
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
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…)
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…)
Issue 2 2011 / 19 April 2011 / Oliver Gordon, Jennifer C. Gray, Hans-Joachim Anders, Alexandra Staerk & Oliver Schlaefli, Novartis Pharma Stein AG and Gunther Neuhaus, University of Freiburg
The risk for patients through spoiled or otherwise adulterated pharmaceuticals has been acknowledged for many centuries and led to the establishment of Good Manufacturing Practice (GMP) and pharmacopoeial guidelines. Besides chemical purity, pharmaceuticals also have to meet microbiological standards, the latter primarily depending on the administration route. Drug products which are injected directly into blood vessels or tissues or that are applied directly into eyes and ears represent a greater infection risk than products which are administered orally or onto intact healthy skin. While parenteral drug products are required to be free from any viable microorganism (USP <71>, Ph. Eur. 2.6.1), oral and topical products are not required to be sterile, but are subject to strict guidelines limiting the number and types of acceptable microorganisms (USP <61> and <62>, Ph. Eur. 2.6.12 and 2.6.13). (more…)
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…)