Those working in pharmaceutical microbiology face an ever–changing environment and the annual conference organised by the Pharmaceutical Microbiology Interest Group (Pharmig) provides an invaluable means for pharmaceutical microbiologists, and other quality personnel, to keep up to date with the latest trends, research and standards.
This 20th anniversary conference, chaired by Pharmig’s current chairman Tony Mayall (Technical Director, UPL), covered various updates on the relevant international standards and hot topics in microbiology such as rapid methods, characterising objectionable organisms and risk-based approaches.
The programme opened with a keynote address by Dr Barry Friedman, a consultant in biotech regulatory compliance and aseptic processing, from the US. Dr Friedman outlined topical FDA 483 warning letters of interest to microbiologists. During his talk Dr Friedan linked the trends with warning letters relating to the recent fungal contamination incident at the New England Compounding Center (NECC). This incident was the most significant case of sterile product contamination during the past 40 years.
The second speaker, Professor Ursula Obst, Head of Microbiology Department, Karlsruhe Institute of Technology, discussed stressed and objectionable micro-organisms, and linked the discussion of ‘when does dead mean dead?’ to biofilm formation. An objectionable micro-organism refers to bacteria or fungi that might be present in a non-sterile product or within a water system of a type that may cause harm to patients. Specialist agars or advanced biochemical techniques are required to screen for such micro-organisms.
Both Professor Obst’s and Dr Friedman’s talks bridged an important gap between what happens in the production process and what occurs within the lab, and how the information needs to be cross-related.
Dr Tim Sandle, head of Microbiology, Bio Products Laboratory, outlined the recent changes to the aseptic environmental monitoring chapter of the USP (chapter 1116) and proceeded to compare and contrast the USP update with EU GMP. The main focus was the move away from the action level as a numerical value and towards the trending of incidents (non-zero count events).
The reason for the USP doing so is based on limitations of metrology in relation to current environmental monitoring methods (in short, the current methods are simply not accurate enough for enumerating micro-organisms accurately). Due to this limitation, the USP argues that it is more sensible to simply trend how many times micro-organisms are recovered and to compare this frequency against the expected pattern of incidents (which, within the highest grade of cleanrooms, is very low).
Current methods are simply not accurate enough for enumerating micro-organisms accurately
Pharmaceutical consultant Jean-Luc Clavelin provided an overview of risk assessment tools and methodologies and applied this to areas of concern to microbiologists, including sterilisation and environmental monitoring. Risk assessment is the buzz term within the pharmaceutical industry at the moment, primarily because both European medicines inspectors, such as the UK MHRA, and the US FDA recommend that ‘risk-based’ methods are adopted. The tools previewed in Clavelin’s presentation included Hazard Analysis and Critical Control Points (HACCP) and Failure Modes and Effects Analysis (FMEA).
Valerie Dunne, QC immunology and Cell Culture Manager at Pfizer (Grange Castle), linked the work of the pharmaceutical microbiologist to the process area, emphasising the importance of the microbiologist ‘walking the floor’. Regulators have commonly voiced the criticism that microbiologists, who are experts in contamination control, are too often locked in the laboratory when they should in fact be out ‘in the field’ advising process staff on the best ways to ensure a safe product. The other role for microbiologists in the production area is to advise on risk assessments and to follow up contamination events.
David Begg, an honorary life member of Pharmig, provided an interesting take on developments in relation to the pharmaceutical industry over the past 20 years together with a look towards the future. The areas covered included regulation (or over-regulation) and the evolution of quality. Begg provided sterling advice on the importance of going ‘back to basics’ and not forgetting what actually matters most: the patient.
The day’s formal presentations concluded with a presentation by Professor of Microbiology and Head of Biology and Biomedical Science at Aston University, Anthony Hilton, who outlined his work on the popular BBC programme ‘Grime Scene Investigation’. Dr Hilton’s presentation was richly illustrated with anecdotes and video footage, and conference delegates went away with lots of information relating to the ‘cleanliness’ of their homes.
Also taking place on both days of the conference were the popular open discussion sessions. The subjects were: quality auditing (run by Jean-Luc Clavelin and Julie Roberts, Quality Consultant, Lilly); environmental monitoring (hosted by Paul Lovegrove-Saville, consultant, PLS Microbiology and Tim Sandle); water systems (chaired by David Keen, Microbiology Head, GlaxoSmithKline and Sharon Johnson, SVP Quality & Regulatory Affairs, Catalent); and objectionable micro-organisms (co-ordinated by Ursula Obst and Andy Martin, MD, ABM Consulting). These sessions provide an opportunity for delegates to bring their own workplace problems to the meetings and seek advice from others working in the industry.
On the second day, proceedings were opened by Professor Willy Verstraete, of LabMET at Gent University, who presented some of the latest university research into micro-organisms, ranging from microbiome research to biofuels. Dr Verstraete was able to communicate quite complex research and translate it into real life, and often practical, applications.
In his second presentation Dr Barry Friedman, looked at non-sterile manufacturing. The focus was upon objectionable micro-organisms and product risks. The USP chapter 1111 provided the basis of test requirements and assessments. Dr Friedman’s assessment included consideration of the numbers of undesired micro-organisms present in a product and the risk factors associated with the patient. The important learning point was that each product, method of manufacture and patient population is different and this should be considered when evaluating any microbial contamination.
each product, method of manufacture and patient population is different and this should be considered when evaluating any microbial contamination
Dr Bharat Patel, Health Protection Agency, gave a presentation related to the 2011 pseudomonas outbreak in neonatal units in hospitals in Northern Ireland. The presentation considered biofilm formation in water systems. The discussion highlighted the importance of environmental controls wherever asepsis is required. This included cleaning and disinfection, as well as the importance of testing and evaluating water systems. The important point was that the hospitals were moving towards adopting some of the same standard and rigorous levels of testing as applied by the pharmaceutical industry.
The fourth feature of the day was a debate on the future direction, use and applicability of rapid microbiological methods. Speaking in favour of rapid methods was Colin Booth, Global Director, QA and Regulatory Affairs Microbiology, Thermo Fisher, with the motion opposed by Dr Nigel Halls, Nigel Halls Consulting. The vote was narrowly carried in Dr Hall’s favour, where the emphasis was placed on the need for traditional microbiology with skilled microbiologists understanding pharmaceutical risks.
The conference ended with a presentation by Neil Raw, of the UK GMP inspector MHRA, who provided detail on the agency’s inspections and risk-based approach to GMP. Also in his presentation, the inspector highlighted some of the most common deficiencies that had been detected by the regulator agency over the past year. Among the top 10 were failures of quality systems and microbiological contamination.
The two-day event included an evening dinner at which many past members of the Pharmig committee and former chairs were present, including Pharmig’s founder Poly Hajipieris. A special tribute was paid to her for having the vision to establish Pharmig at the turn of the 1990s.
Pharmig began as a forum for microbiologists and has since evolved into the UK’s foremost professional body for pharmaceutical microbiologists. In recent years, it has extended its microbiological expertise into related industries, such as healthcare, personal care, medical devices and toiletries.
The next event – PCT 2013: International Contamination Control – at the Oxford Belfry on 26 - 27 February 2013, will be a two-day conference for the pharmaceutical, cosmetic and toiletries industries. For more details visit www.pharmig.org.uk.