Microbiological Environmental Monitoring of a New Facility Manufacturing Oral Dosage Forms for Commercial and Clinical Trial Supply

BACKGROUND
A new pharmaceutical company approached us to provide microbiological support for their non-sterile manufacturing facility. In particular, the demonstration of an effective environmental monitoring programme was essential in order to obtain MHRA authorisation for the manufacture of oral solid dosage forms (tablets, capsules) and had to be achieved within a challenging timeframe.

EXECUTIVE SUMMARY
The client was not performing any environmental monitoring when we were first approached and were only one month away from an MHRA pre-inspection visit. An initial determination was made to benchmark the microbiological contamination status throughout the facility. These results were used to formally assess the risk of microbiological contamination occurring in finished manufactured product and a number of recommendations made to reduce the ongoing risk of contamination. From this a suitable environmental monitoring programme involving the scheduled collection and analysis of settle / contact plates and swab samples was agreed with the client. In addition, a microbiological training programme was designed and delivered to the staff working on the manufacturing site as a further measure to improve cleanroom practice.

The client acted on the recommendations in the report and a subsequent visit was made to report the microbiological cleanliness of the facility. Our risk assessment and recommendations were reviewed by the MHRA during their inspection visit and were found to be satisfactory.

We now continue to provide ongoing support for the facility as they move into manufacturing; data trending and recommendations are routinely made to help maintain cGMP compliance in respect of environmental monitoring. Throughout the programme we have had to be very responsive and flexible as the client's exact requirements evolved as the unit was established. As a consequence we developed flexible pricing and schedules to reflect those changing needs.

OUR APPROACH
Our support was based around our fully equipped microbiology laboratories, and the experience of our Senior Microbiologist in setting up environmental monitoring programmes in cGMP facilities. A six step approach was adopted:

• Initial site visit and sampling
• Hazard / risk assessment
• Training of cleanroom staff
• Scheduled routine monitoring visits
• Trending of data
• Ongoing recommendations and feedback

Initial Site Visit

An initial site visit was required in order to establish the following:

• Familiarisation with the overall manufacturing process / working practices
• To record the facility layout, room identities, airflows and people traffic. This information was used to agree appropriate sampling plans with the client
• To take initial contact and settle plate samples. These were used to establish the baseline level of microbial contamination before the environmental monitoring programme was initiated
• To establish the logistics of sampling at the site, returning to the Agenda1 for subsequent analysis
• To gather data for a risk assessment

Hazard / Risk Assessment
Using the facts and microbiological data gathered from the initial site visit a comprehensive risk assessment was completed. This identified the key microbiological hazards and the critical control points throughout the facility and proposed recommendations for improvement of existing cleanroom practices. Finally the level of risk for microbiological contamination of a manufactured product was assigned and justified.

Training of Cleanroom Staff
Client staff were trained by Agenda1 using the following programme:

• A presentation was delivered detailing basic microbiological methodology and background, sample collection, plating and incubation techniques, sources of contamination, good hygiene / cleanroom practice and the implications of microbiological contamination of manufactured pharmaceutical products
• A simple written test was devised to ensure that the key training information had been successfully delivered
• Successfully trained staff were issued with training certificates

Scheduled Routine Monitoring Visits
At each monitoring time point the microbiologist travels to the site, collects samples (air settle plates, swabs and surface contact plates), returns to the Agenda1 laboratories and initiates the analysis - all within the same day. The results are turned around within one week following incubation, counting and data checking.

Trending of Data
Data from each visit is collated to permit data trending. As the database grows the trended data will be used to establish alert and action limits and to assign cleanroom classification.

Ongoing recommendations and feedback
The results of each scheduled visit together with the trended data are fed back to the client. An interpretation of the data and recommendations (e.g., advice on changing the visit frequency) are outlined in a summary report.