: In order to stay within regulatory guidelines, what are some must-have technologies that a pharmaceutical company should implement to meet microbial monitoring requirements?
You cannot have a secure environmental monitoring (EM) program without quality culture media. To validate fertility of the media, a growth promotion test must be performed on each incoming batch with strains both referenced in the pharmacopeia as well as those isolated from the plant. High-quality reference strains as well as customized plant isolates can be purchased commercially and deliver accurate, consistent results.
EM media must also be able to neutralize the harsh disinfectants used in pharmaceutical manufacturing facilities. Suitable testing should be performed to validate efficacy of neutralization before first use and repeated any time a change of disinfectants is made.
The sampling process itself should be standardized since different contact times and different sampling pressures lead to different recovery results. Sampling devices such as contact plate applicators and frequent re-training of the persons doing the sampling can help mitigate inconsistencies.
Data Integrity is of critical importance. To ensure the EM data are accurate, trustworthy and reliable, any source of human error should be avoided as much as possible. Since any manual step is a potential source of error, it would be ideal to automate the reading step and the administrative steps.
Lastly, data trending. The clean areas around the very protected cleanroom zone must be sampled on a regular basis and colonies detected should be identified systematically. Both the number of colonies and identification of the microorganisms found must be noted in a trending software tool. Any change in count and identification is valuable information in case of contamination. The review of those data on a frequent basis should be defined accordingly.
: If a pharmaceutical company is looking to upgrade its microbial monitoring and testing processes, are there some relatively easy, first steps to take? What do you recommend and why?
Regular reviews of SOPs related to microbial monitoring should be performed and revised as necessary based on trends and internal audits to assess risk. It is also important to visit the production floor on a regular basis to uncover any changes that have been implemented through discussions with production managers to ensure no changes are missed by the EM team. (For example: new people in the production facility including cleaning personnel, change in suppliers for gloves, HEPA filters, gowning, raw materials.)
: Do you foresee pharmaceutical companies implementing the strict microbial monitoring strategies used for sterile product production on other types of products – such as solid dosage?
Data Integrity will always be important regardless if the production is for sterile or non-sterile products because accuracy of data can impact drug safety. Hence, reducing all human-related sources of error should be optimized independent from the facility type.
Identification of “objectionable microorganisms” is another topic that continues to be of importance for all drug types; including combination products such as nose sprays.
Consequently, the EM process including actions to improve data integrity, ensure the performance of culture media and any other action to optimize of the EM process should be no less importance than in sterile production sites.
: What are some best practices a pharmaceutical company should put in place to collect, store and analyze microbial monitoring data?
All data should be traceable to their respective sampling points. Ideally, a barcode system is implemented to ensure any missed plate can be detected. Software allowing the management of the sampling plan, data collection and trending can be very valuable and reduce human error.
Elimination of paper-based records in favor of digitalized data can increase data integrity and software can guarantee data cannot be modified or deleted and can add 21 CFR Part 11 compliance for traceability.
: In the near future do you see pharmaceutical companies moving away from large cleanrooms to processing sterile products in isolators, gloveboxes or RABS? If so, why?
An increasing number of manufacturers are producing personalized medicines whose batch size is inherently smaller than classical drug production.
Since many of these drugs have short shelf lives and are often administered before final sterility test results are available, it is critical to reduce risk as much as possible.
Automated testing that can be easily performed near the manufacturing area can bring faster time to result and enhance the compliance, productivity and safety of the production facility and the drugs they produce.