Top 8 FAQs to navigate the EU GMP Annex 1 Revision on environmental monitoring

Sterile manufacturing represents one of the hardest challenges in pharmaceutical and medical device manufacturing. It is a process that requires careful planning, trained personnel, rigorous checks, and specialized facilities and equipment, as failure to ensure sterility can lead to life-threatening consequences for a patient. To minimize risk, compliance to regulatory guidelines that define the minimum requirements for pharmaceutical manufacturers to meet good manufacturing practice (GMP) standards is essential, and it is recommended that any interruptions to monitoring operations are avoided.

We spoke with Dr. Eric C. Arakel, global product manager for sterility testing and air monitoring at Sartorius, to find out more about environmental monitoring programs and to help answer the frequently asked questions (FAQs) about microbiology air monitoring and meeting the new EU GMP Annex 1 revision.

For a more detailed discussion around this topic, register for the upcoming webinar titled ‘Microbial air monitoring: Navigating the regulatory landscape’ to be hosted on June 10, 2022:

1. Why is continuous air monitoring with gelatin membrane filters a particularly good method to ensure product safety?

Whilst Annex 1 of the EU GMP guide calls for an air sample with a minimum volume of 1m³ to be taken per sample location, this volume is too low to reliably judge the air quality of a manufacturing environment during a typical 8 hour working shift. As such, continuous air monitoring covering the complete production process, along with multiple sample points is a great way to improve product safety.

In addition, gelatin membrane filters, as found in the Sartorius MD8 Airscan^® system, don’t dry out like a similar agar plate would, and are therefore suitable for use during the whole 8-hour period.

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

One of the key advantages of the gelatin-membrane filter over agar-based impaction is that it allows 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) and this can have an impact on the recovery rate of microorganisms. Annex 1 recommends intervention-free sampling, and this is basically what the gelatine membranes deliver.

For further information, download this application note, which explores this in greater detail – and conclusively shows that gelatin membranes manufactured by Sartorius Stedim Biotech GmbH are qualified for continuous air monitoring in industrial pharmaceutical production environments for a whole 8h work shift without the need for human intervention.

3. What is the procedure to estimate bio-pollutants in indoor environments?

Our gelatin-membrane filters have a high retention capacity. You can effectively capture over 96-99% 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.

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

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 virus. 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.

5. Can the gelatin filters be used to sample for longer than eight hours?

Gelatin filters have the potential to be used for continuous air monitoring for longer than eight hours. How long however does depend on the relative humidity of the environment because the filters are hygroscopic in nature and the residual moisture drawn from the surrounding environment encapsulates the sampled microorganisms preventing their desiccation. Our customers typically use the filters in a working range of 30-60% RH, with an operational max of 85%.

6. How do you disinfect the device?

The MD8 Airscan^® is built in line with the airflow to enable isokinetic air sampling. The sampling head and the entire flow path can be decontaminated with vaporized hydrogen peroxide (VHP).

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

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 onto 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.

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

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 of how long microorganisms survive. However, I don't see the need for long-term storage of such filters.

Want to know more about the impact of EU GMP Annex 1 revision on environmental monitoring? Register for this free webinar>>