Wednesday, 4 May 2016

Microbiological safety of medicines discussed in Oxford

The safety of medicines is of great importance, needing to be of the required formulation and contamination free. Recently, in Oxford, U.K., pharmacists and microbiologists came together to review best practice.
The event, held on March 2 and 3, 2016, was hosted by the Pharmaceutical Microbiology Interest Group (Pharmig.) Day one of the event was more general, and it looked at the best strategies for ensuring the environments within which medicines are prepared and put into final containers is safe. The second day was more specific, assessing an important subject of avoiding bacterial and fungal spores entering into products. A unifying theme with the second day was the use of special, highly aggressive disinfectants called as "sporicides."
The two day meeting drew over 50 delegates, over 20 exhibitors and specialist speakers. The meeting was held in a new hotel — The Oxfordshire — which overlooks the sprawling delights of Oxfordshire, the epitome of the English countryside (Digital Journal has also reviewed the hotel and its facilities in a separate article.)
A view from The Oxfordshire hotel.
A view from The Oxfordshire hotel.
The first day, facilitated by the chair of Pharmig David Keen (from GlaxoSmithKline), began with a presentation from Tim Sandle (speaking in an independent capacity). Dr. Sandle compared the differences between U.S. and European guidances for assessing contamination in cleanrooms. A cleanroom is a specially designed, contained room, with filtered air (through a HEPA filter) and a high level of air-changes, so that any contamination is (in theory) removed from the room. The problem with cleanrooms arise when people are placed in them, for people continually shed skin detritus and some of these very small particles (on the micronmeter scale) act like rafts, carrying bacteria.
Pharmig s David Keen addresses the meeting.
Pharmig's David Keen addresses the meeting.
The key difference between U.S. and European regulations, Dr. Sandle explained, is for the cleanest areas the U.S. approach is to count non-zero events and to react to adverse trends; whereas the European approach is to react to actual counts, and assess the individual impact of each.
The second presentation was from David Keen, which looked at a strategy for rolling out an environmental monitoring program. Of particular use was looking at where points of microbial contamination are likely to occur and ensuring samples are taken in these locations, rather than putting out agar plates away from where work is actually going on. This may seem like common sense, but Mr. Keen pointed out, from his experience of visiting different pharmaceutical manufacturing sites, there is a bewildering array of practices.
Conference delegates assemble in-between presentations  at The Oxfordshire Hotel  Oxford.
Conference delegates assemble in-between presentations, at The Oxfordshire Hotel, Oxford.
Dr. Sandle presented again for the third presentation. This looked at the best methods to capture both bacteria and fungi. This is not straightforward because the organisms — from two different microbial kingdoms — prefer growing on different media. The trick is to develop an incubation strategy, examining the factors of time and temperature. Dr. Sandle outlined a recent paper he had written, which recommended using a lower temperature first (20-25 degrees Celsius), which encourages fungal growth and does not kill bacteria, and then incubating at a higher temperature (30-35 degrees Celsius). The risk of not doing so could lead to a destruction of lytic cellular enzymes, which can kill some fungi.
Conference delegates discussing new technologies with exhibitors  at the Pharmig event.
Conference delegates discussing new technologies with exhibitors, at the Pharmig event.
The fourth presentation was delivered by pharmaceutical consultant Julie Roberts. This looked at how to identify microorganisms recovered from the environment and the differences between phenotypic technology (which looks at how an organism interacts with its environment) and genotypic methods, which look at the microbial genome. The presentation also discussed how many identifications should be performed in order to create a meaningful picture of the production environment.
Global audit specialist Julie Roberts discusses best practices for microbiological identification at...
Global audit specialist Julie Roberts discusses best practices for microbiological identification at the conference.
This was followed by a presentation by Erika Notman (a pharmaceutical sector consultant.) This presentation consider case studies for investigating high microbial counts and the sorts of things to look for, such as poor cleaning techniques or environmental control failure.
The final presentation from day one was delivered by Julie Roberts and this touched on the subject of data integrity. Readers of Digital Journal will be aware about this subject as it touches on either the mis-recording of data or even the falsification of data, designed to make a drug product appear safe when it is, in fact, adulterated.
At the end of the first day, delegates had the opportunity to walk the hotel grounds. Too late for a round of golf (for those interested in the small ball and stick sport); the views were nevertheless impressive.
The golf course at the conference venue - The Oxfordshire hotel.
The golf course at the conference venue - The Oxfordshire hotel.
The second day was orientated more towards the health sector and hospital pharmacy units. There were aspects, however, of interest to the pharmaceutical sector as well. The day was chaired by Tim Sizer, who is the Regional Pharmaceutical Quality Assurance Officer South West.
Tim Sizer  the Regional Pharmaceutical Quality Assurance Officer South West  chairs day two.
Tim Sizer, the Regional Pharmaceutical Quality Assurance Officer South West, chairs day two.
In preparation for the second day  folders ready  PowerPoint presentation loaded.
In preparation for the second day, folders ready, PowerPoint presentation loaded.
The aim was to provide an updated overview of the risks associated with bacterial and fungal spores within the aseptic preparation environment (where medicines intended to be sterile are formulated and filled.) The day also set out to review recent incidents causing harm to patients and to discuss new guidance, such as the Medicines and Healthcare products Regulatory Agency (MHRA) — the U.K. medicines regulator — new "Guidance to Specials Manufacturers."
The first presentation of the day was from Tim Sandle. Here Dr. Sandle provided an overview of spores, both bacterial and fungal, and explained why they are so resistant to common disinfectants. With bacteria, this is due to a three-layered spore coat, and the ability of some spores to stick together. For fungi, the problems are with the sheer number and the ability of some to secrete an enzyme that can inactivate disinfectants. While the use of a potent sporicidal disinfectant is important, the key message from the presentation was to focus on a good biocontamination control strategy.
A conference delegate peruses Pharmig literature  during a mid-session break.
A conference delegate peruses Pharmig literature, during a mid-session break.
The second presentation of the day was delivered by Tim Sizer. This ran through some of the more recent pharmaceutical and pharmacy contamination events. These included the infamous New England Compounding Center (NECC) issue, where contaminated vials of a steroid were distributed across the U.S. The case count is still being tallied up, and stands at almost 800 infected and over 70 deaths.
The third address was from Mark Oldcorne, who is the All Wales Quality Assurance Specialist Pharmacist. In this presentation the advantages gained in reducing contamination events from different types of disinfection were discussed. Data was presented showing sanitization by gassing to be the most effective, followed by the use of spraying and wiping or a sporicidal chemcial. Without wither of these two measures, other data indicated a low but ever present microbial contamination risk.
A key part of many conferences is the opportunity to discuss test kits and disinfectants with suppli...
A key part of many conferences is the opportunity to discuss test kits and disinfectants with suppliers. The photograph shows delegates interacting with suppliers.
The fourth presentation was delivered by Rachel Blount, who is the Global Validation Manager of the company Ecolab. The presentation was designed to enable the user to interpret the methods adopted to validate disinfection efficacy. Here Rachel Blount explained the different international standards for testing disinfectants to show that they actually work.
The next presentation was again by Tim Sandle. In this second presentation, Dr. Sandle set out to consider the types of sproicidal agents available on the market and the limitations of their use. The choice of sporicides is quite narrow, once health and safety issues and ease of use have been considered. These are either chlorine based (such as chlorine dioxide, hypochlorus acid, chloramine, or hypochlorite) or oxidizers like peracetic acid or hydrogen peroxide. Dr. Sandle was keen to emphasize that the claims of manufacturers should not be taken at face-value and laboratory studies were needed to confirm biocide effectiveness.
The day also included a workshop, where delegates simulated disinfecting and transferring vials. Here there was a variety of different practices, indicating that a common standard was required. Based on this, the pharmacists present undertook to continue to develop best practice for the transfer disinfection process and potential alternatives.
Delegates undergoing a practical exercise to learn about good disinfection practices.
Delegates undergoing a practical exercise to learn about good disinfection practices.
The practical including advice on how to disinfect the outer surfaces of vials, used to store medicine, correctly.
A pharmacy technician learns the correct procedure for disinfecting a vial of medicine.
A pharmacy technician learns the correct procedure for disinfecting a vial of medicine.
There was also an opportunity learn about spraying disinfectants, with a view to getting the right quantity onto a wipe.
A delegate practices the application of a disinfectant onto a cleaning cloth.
A delegate practices the application of a disinfectant onto a cleaning cloth.
The final presentation was from Mark Oldcorne, which considered some best practices from aseptic processing, focusing on materials being transferred into and out of controlled environments.
The two day Pharmig event was well organized and helped to reinforce best practices and the appropriate standards for microbiological contamination control.
A sign for the Pharmig event at The Oxfordshire Hotel  Oxford.
A sign for the Pharmig event at The Oxfordshire Hotel, Oxford.
Posted by Dr. Tim Sandle