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Harmonizing the industry and improving confidence through risk-based microbial testing

The integrity of microbiological test data is critically important to ensure the safety of both the pharmaceutical products and the patients who receive them. One approach to ensure the quality of drug products is to implement second-person verification of microbial testing; however, requiring second-person verification of all data is time-consuming and cost-ineffective, particularly when performing low-risk tests. The BioPhorum Microbial Control workstream realized that no standardized recommendations existed regarding when second-person verification should be performed. The workstream recently published a paper, Risk assessment of traditional culture-based microbiological tests requiring contemporaneous verification, that describes a risk-based approach with enhanced controls as being a more effective way to manage data integrity issues than second person verification on all tests. This guidance will help companies determine when second-person verifications are necessary, and the controls needed to ensure data integrity.

The integrity of microbiological test data is critically important to ensure the safety of both the pharmaceutical products and the patients who receive them. One approach to ensure the quality of drug products is to implement second-person verification of microbial testing; however, requiring second-person verification of all data is time-consuming and cost-ineffective, particularly when performing low-risk tests. The BioPhorum Microbial Control workstream realized that no standardized recommendations existed regarding when second-person verification should be performed. The workstream recently published a paper, Risk assessment of traditional culture-based microbiological tests requiring contemporaneous verification, that describes a risk-based approach with enhanced controls as being a more effective way to manage data integrity issues than second person verification on all tests. This guidance will help companies determine when second-person verifications are necessary, and the controls needed to ensure data integrity.

According to Hilary Chan, Principal QC Scientist at Takeda, some sites performed 100% verification of microbial testing plates, resulting in demands on personnel leading to significant time delays. By implementing the BioPhorum recommended approaches for second-person verification, Chan believes they will reduce risk, improve data integrity, and limit demands on personnel through more focused efforts. “In general, the approaches reduce the risk of false-negatives and false-positives. It also helps to confirm the absence of data integrity gaps or risks, especially for high-risk samples like sterility, by providing a higher level of confidence in the integrity of the results. Second-person verification may not be practical or necessary for all tests, and the guidance helps us to determine what the risks are and implement secondary verification where appropriate,” said Chan.

Michael Knight, Director, Microbiology and Environmental Monitoring at Genentech (Roche) explained that they began implementing the risk-based approaches globally two years ago and have already begun to see benefits. “The primary benefit is compliance. Prior to this risk assessment we had verification on some assays, such as sterility, but there was no unified documented strategy as to which assays required verification and which didn’t. With this risk assessment, I’m confident going into inspections, and it really strengthens the acceptability of this approach with regulatory audits,” said Knight.

Cheryl Essex, former Head of Microbiological Control at Sanofi, also reported that their sites were not harmonized in their approach to second-person verification and, while some were risk-based, there was no documented risk assessment. Sanofi adopted the BioPhorum approach by completing a global risk assessment on all manual analysis of microbiological samples. It concluded that when best practice lab controls are in place, only higher risk samples warranted a systematic four eyes count. “Adopting the BioPhorum approach was the right choice. It allowed us to drive harmonization with more confidence in our data integrity strategy. We have successfully defended the approach in inspections. And across our biologics drug substance sites alone, this approach saves second person verification of more than 10 million samples per year.”

Impacting the industry – adoption by USP Recently, the risk-assessment paper was specifically referenced by experts on a USP panel and was used as a basis for their changes to USP 1117, which recommends second-person verifications according to risk. “The USP recommendation, based on our paper, is a great move for our industry to incorporate our recommendations. This allows the guidance to be more accepted to an inspector than if it was just an industry publication. This is a clear example of an industry collaborating on a challenging topic, and the USP hearing the voice of the industry and incorporating our proposals,” said Knight. With the USP recommendations, the industry is one step closer to a more unified approach, and the workstream members hope that similar guidance based on BioPhorum recommendations for second-person verification are adopted by other global regulatory authorities.

The workstream encourages all BioPhorum members to review the paper and adopt the recommendations, as more companies who adopt this approach will lead to improved consistency across the industry. “A challenge may be employee awareness and training of people who are not experienced with the use of risk-based tools. Over time, more people will feel comfortable with it and see the benefits,” said Chan. Even though change can be difficult, the benefits to companies can be long-lasting by improving time management and data integrity with the recommended risk-based approaches to second-person verification.

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