The Rapid Micro Blog

Our blog will keep you informed of new and noteworthy technologies, reviews of recent publications and presentations, upcoming conferences and training events, and what's changing in the rapid and alternative microbiological methods world.

ECA Rapid Methods Conference a Huge Success

In December 2013, the European Compliance Academy (ECA) hosted their annual rapid microbiological methods conference and it was, as is usually the case, a huge success! Axel Schroeder and Jessica Sturmer, both of Concept Heidelberg, along with Program Chairperson Dr. Sven Deutschmann, welcomed attendees to Barcelona, Spain, for this yearly event.

The two-day conference and an additional workshop on statistics provided attendees with a unique opportunity to evaluate the new developments in RMM systems, experiences in validation as well as implementation within the pharmaceutical industry. Attendees also learned about the expectations of authorities and recent developments in regulatory requirements. Experts, end-users and suppliers provided insights in the routine use of RMMs and during the statistics workshop, practical examples and information about the interpretation of microbiological validation data.

The conference opened with Dr. Tony Cundell providing an overview of the USP’s revision to chapter 1223 and the development of a new rapid sterility test chapter.  This opening presentation was very provocative and provided for quite an interesting Q&A session, especially from RMM technology suppliers and validation experts.  Some were left scratching their heads trying to understand the direction the USP is taking, and this is the topic of a more comprehensive discussion I provided in a separate blog posting (click here to read).

Stephen Wicks (EDQM) then provided an overview of the current status of the revision to European Pharmacopoeia chapter 5.1.6.  Based on his discussions, the draft chapter appears to be better aligned with the new PDA Technical Report No. 33. Additionally, new validation examples will be proposed which will include rapid sterility testing using membrane filtration, a quantitative assay for the enumeration of microorganisms using solid phase cytometry, and a PCR-based microbial identification method. It is anticipated that the working party will meet in early 2014 to finalize the revision, followed by a public inquiry in Pharmeuropa. Following public comment, the working party will put the finishing touches on the draft, with a mid to late 2014 publication date.

Following Stephen’s presentation I presented an overview of the revision to PDA Technical report No. 33, which was published in October 2013. I recently published this overview in American Pharmaceutical Review, and you can download the article by Clicking Here.

Jeanne Moldenhauer (Excellent Pharma Consulting) followed with a lively discussion on rapid sterility testing and the methods that have been approved by the regulators in early submissions. She also described the reasons why a number of companies became disillusioned with their rapid sterility methods and abandoned their use. She finished with suggestions for how the industry can prevent this type of occurrence from happening in the future.

Next, Judy Madden (Celsis) provided a short presentation on validating a rapid sterility test by direct inoculation using the ATP bioluminescence Celsis Advance System.

This was followed by an end-user’s validation perspective of the Celsis system. Dr. Erik Wilkens (Novartis) discussed a proposed workflow and validation plan for a direct inoculation method in which a non-filterable product or device is enriched in a liquid medium, followed by centrifugation of the media and then introduction into the Celsis system.   

David Jones (Rapid Micro Biosystems) provided a short presentation on the second generation Growth Direct System. He discussed automating bioburden, environmental monitoring and sterility testing using their autofluorescence technology.

This was followed by an end-user’s perspective of the same Growth Direct technology. Oliver Gordon (Novartis) shared their feasibility and neutralization studies, which included processing actual EM samples (active air and surface samples).  The Growth Direct results were comparable with the classical method of visually observing and enumerating CFU’s on agar plates. 

A short presentation by Pall Corporation discussed a case study on factors to consider for rapid method system implementation.

Next, Dr. Marcel Goverde (MGP Consulting) gave an excellent overview of helpful literature and online resources that offer validation and implementation guidance. 

This was followed by another short presentation by a RMM supplier. Tim Russell (TSI) provided an overview of their BioTrak real-time viable particle detection system.  The presentation included a discussion of laser induced intrinsic fluorescence, how to minimize false positive results, and how to utilize the system’s built-in collection filter for subsequent microorganism analysis and identification. 

Dr. Emiliano Toso (Merck Serono) then shared his experiences with in-process control testing by traditional, innovative and next generation methods in order to avoid large-scale virus contamination events, such as those caused by Vesivirus and Mouse Minute Virus.  Focusing on molecular methods, he described reverse transcriptase gene amplification techniques, next generation and deep sequencing methodologies. 

The next speaker was Dr. Franz Gruber (Baxter) who described the long-term experience regarding alternative Mycoplasma testing according to European Pharmacopoeia expectations.  He provided an overview on an RNA-based methodology for nucleic acid extraction and amplification, handling, storage, and stability, and the relationship between the alternative method and reference preparations.

Dr. Sven Deutschmann (Roche Diagnostics) provided a summary of a PCR-based method for the detection of Leptospira.  He described the regulatory expectations (FDA, EMA and the Japanese PMDA) for in-process testing of Leptospira in CHO-cell processes.  Validation approaches for detection limit, specificity, robustness and limiting cross contamination were discussed. 

bioMerieux provided the next vendor short presentation and this focused on their BioBall product.  David Myatt described the very precise flow cytometry and freeze drying manufacturing process that allows the consistent generation of a stable and precise low level inoculum. 

Dr. Edwin van den Heuvel (UMC Groningen) and Dr. Pieta Ijzerman-Boon (MSD) provided an introduction into the statistics workshop that they presented following the main conference.  They discussed statistical detection mechanisms, validation issues and validation experiments. Not for the faint hearted, this intense statistical overview consumed the attendees with guidelines on recommended inoculation levels, replicate numbers, false positives and false negatives, and of course, statistical models.

The final presentation by Dr. Sebastien Ribault provided insights into whether there exists a need for rapid methods as in-process controls during biotech processing.  The impact of using RMMs on projects timelines was also considered.

As you can see from the caliber of expertise of the speakers, this past ECA conference on rapid microbiological methods promoted lively discussions (and definitely debate), the sharing of best practices and most importantly, a sense of camaraderie among fellow scientists and experts in the field of RMMs.

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