The impact of EU GMP Annex 1 revision on environmental monitoring

The EU good manufacturing practice (GMP) guide has helped with the manufacture of many sterile medicinal products. The EU GMP Annex 1 revision on the manufacture of sterile medicinal products specifies that in Grade A areas, any growth detected in one cubic meter of sampled air should result in an investigation. To minimize risk, it is therefore recommended that you avoid any interruptions to monitoring operations.

In this on-demand webinar, Dr. Eric C. Arakel, global product manager for sterility testing and air monitoring at Sartorius, talks about environmental monitoring programs and how the Annex 1 revision could impact you. Arakel also presents solutions for continuous, intervention-free active air monitoring for a typical manufacturing period of eight hours.

Read on for highlights from the live Q&A session or register to watch the webinar at a time that suits you.

Q: Can the gelatin filters be used to sample for longer than eight hours?

EA: Yes, the filters have the potential to be used longer than eight hours. It depends on the relative humidity of the environment. For example, a decent relative humidity in the working range of 30% to 60% should be fine.

Q: How do you disinfect the device?

EA: The MD8 scan is built in line with the airflow. The entire device can be decontaminated with vaporized hydrogen peroxide (VHP). It's completely compatible with PHP decontamination.

Q: Is it possible to use gelatin filters in isolators? If yes, how do you transfer them onto agar?

EA: Yes, it is possible to use gelatin-membrane filters in isolators. Once the sampling is complete we detach the gelatin-membrane filter which is encased in a plastic housing and then transfer this on to agar. You can do this in one of two ways, either you gently slide the filter onto an agar surface, or you use the agar plate to pick up the filter. The moisture content dissolves the membrane filter on the surface of the agar plate. Next, you can either take the filters out of the isolator in the Ziploc bags over to the microbiological testing lab where you then transfer them onto an agar plate, or you could preload the isolators with your agar plates. Once the sampling is done, just pick up the filter using the agar plate without touching it.

Q: What are the key advantages of the gelatin-membrane filter over the agar-plate impaction method?

EA: One of the key advantages of the gelatin-membrane filter over agar-based impaction is that it is basically continuous long-term sampling. You don't have to swap out the filters as often as you would the agar plates. There is a loss of 4% to 12% of water with every cubic meter of air that is sampled for agar plates compared to 0.3% using gelatin-membrane filters. Annex 1 recommends intervention-free sampling and this is basically what the gelatin membranes deliver.

Q: Are there any requirements, standards and specification limits for processing and filling areas in the food industry?

EA: The only regulation that I am aware of is the ISO 8573 for the microbiological testing of compressed air which is under review at the moment. We are trying to see if gelatin-membrane filters are compatible with sampling in compressed air. I would assume that you would apply similar principles of quality risk management and contamination-control strategy for environmental monitoring. I think this is also a site-to-site decision, since you would want an early warning system in place which will help you implement any corrective actions.

There is an increased risk of exposure of personnel to pathogens in many of the food manufacturing sites. One such example is an outbreak of COVID in the meat-packaging plants during the pandemic. This is where you want an environmental monitoring system because you can capture both microorganisms as well as viruses. Our gelatin-membrane filters are used quite commonly for tracking the airborne transmission of COVID. However, I'm not fully aware of which regulations to quote here for the food manufacturing industry, but I would assume there are some out there.

Q: What is the procedure to estimate bio-pollutants in indoor environments?

EA: Our gelatin-membrane filters have a high retention capacity. You can effectively capture over 96% of the viruses and capture particles smaller than 80 nanometers. This means you could use these filters for an indoor environmental monitoring program in crowded spaces.

Q: Gelatin filters can capture both viruses and microorganisms, but virus sampling is not required. Is this right?

EA: This is correct, however, there are advantages to sampling viruses. The COVID-19 pandemic is a perfect example of monitoring indoor environments such as workspaces for the spread of the viruses. In addition to this, you could also gauge the presence of adventitious viruses in your manufacturing facility. Although not part of the regulations, I would see a use for such virus sampling during monitoring as well.

Q: After eight hours of continuous sampling, what should be the maximum time between sampling and analysis?

EA: You could transfer membranes onto agar plates immediately - either directly within the isolator or slip them into the Ziploc bag then walk them over to the microbiological testing lab where you could transfer this onto the agar plates. We have not done tests to see how long the microorganisms survive on the filters without transferring them onto agar. However, we have subjected them to eight hours of sampling, sampled them for 30 minutes and then subjected the membranes to continuous streams of air. The microorganisms were still viable following the eight hours of continuous air filtration. This gives a rough idea as to how long microorganisms survive. However, I don't see the need for long-term storage of such filters.

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