News & Events

DPS attend PDA Microbiology Conference in Berlin

Wednesday 18 February 2015

Aidan Harrington (DPS Senior Consultant) attended the PDA’s Annual Microbiology Conference in Berlin on Feb 17/18th 2015.

Pharmaceutical Microbiology and Contamination Control are high on the agenda of the regulators, as revealed by the analysis of FDA Warning Letters for FY (Fiscal Year) 2014 which unexpectedly revealed that the Code of Federal Regulations (CFR) Paragraph 211.113 "Control of microbiological contamination" was at the top of the most observed deficiencies.  This section from the CFR was absent from the top 10 of the ranking list of the most frequent GMP deviations in 2013.

In addition to addressing Contamination Control Strategies for new and existing facilities, the conference also covered the following:

  • Regulatory and Scientific Updates, including an overview of possible modification to microbiological requirements from the upcoming Annex 1 update
  • Sterile & Non Sterile Manufacturing
  • Pharmaceutical Water Systems & Regulatory Update
  • Endotoxin Detection & Regulatory Challenges
  • Microbial Detection: Novel Technologies & Applications
  • Contamination Control

Some key points to note:

  • The proposal  to use of Rapid Microbiological Methods will be incorporated into various sections into the upcoming Annex 1 update. This is to acknowledge the advances in this technology and for example that there are short-shelf life products being developed that cannot wait for the results of traditional microbiology testing for release of these products. The consensus was that the regulators were ready to embrace this technology, but that it is the industry who have showed a misguided reluctance to move forward due to perceived regulatory concerns.
  • A new technology for real time microbial monitoring of water systems was presented.  It is based on the detection of fluorescence emitted by cellular metabolites, which distinguishes between viable and non-viable particles. On detection of microorganisms, the system has the capability to ‘grab’ that sample and perform traditional microbiological recovery and growth procedures. A key challenge for this system is  that most microorganisms that are detected cannot be cultured in traditional medium (a phenomenon known as ‘viable but not culturable’), hence counts are much higher using this method compared to the traditional plate count method.  This presents a significant challenge to the current acceptance criteria for high purity water systems.
  • Endotoxin testing is receiving a lot of attention from the FDA and the industry in general due to the phenomenon of Low Endotoxin Recovery (LER) first reported by Genentech in 2013.  This is where the endotoxin content of certain formulations of biological drugs was underestimated when using the traditional  endotoxin LAL test method due to masking effects by product components. The FDA has expressed concerns since endotoxin contamination could now occur during manufacturing that cannot be detected by the available test methods. The FDA is actively challenging Biotech organisations with respect to LER and expecting that there is detailed scientific knowledge and understanding of the test methodologies used.
  • Aseptic Manufacturing facilities, according to Rick Friedman of the FDA ‘requires a strict design regime, not only in the process area, but on the interactions with surrounding areas and the movement of people, materials and equipment so as not to compromise the aseptic conditions’. The oversight of the aseptic manufacturing program requires an approach that is multi-disciplinary, with clarity around all aspects from roles and responsibilities to the continuous improvement program. The role of the microbiologist (the ‘Process Microbiologist’ is a  key, yet often overlooked role in ensuring continuous control in aseptic areas from design through to ongoing operations.


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