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.