The pharmaceutical industry is a dynamic and rapidly evolving field, with data integrity and rapid microbial methods (RMMs) playing pivotal roles in shaping the future of microbiology labs. These elements are not just integral to the functioning of labs but are also transforming the way they operate, bringing about increased accuracy, efficiency, and reliability in drug development and testing processes. Let’s delve a little deeper into the significance of data integrity and RMMs, providing detailed examples of their application and impact on modern microbiology labs in the pharmaceutical industry.
Data Integrity in Microbiology Labs
Data integrity, defined as the maintenance of and the assurance of the accuracy and consistency of data and metadata over its entire life cycle, is a critical aspect of microbiology labs. It ensures that the data generated is reliable and can be trusted for decision-making processes.
Violations involving data integrity continue to be observed during FDA inspections. Without strong data integrity practices, microbiology labs will have less confidence in their data to make informed decisions and meet regulations. Whether data are inadvertently or purposefully manipulated, any gaps in the security of data reporting and handling introduce significant risk to operations and to patients.
For example, data integrity concerns cited in FDA form 483 observations include:
- Failure to implement adequate controls to support the integrity of electronic data and to ensure that only appropriate individuals had administrative rights
- Human errors through manual transcription of microbiological data or incorrect counting of colonies
- A lack of control to prevent deletion of raw data
- A lack of training protocols for the cGMP training of employees, including training personnel to prevent and detect data integrity issues
- A lack of audit trail review and inadequate data review procedures
In the pharmaceutical industry, data integrity is crucial for maintaining regulatory compliance, ensuring patient safety, and enhancing the overall quality of pharmaceutical products. For example, in the development of therapeutics or cell and gene therapies, data integrity plays a crucial role in ensuring safety and efficacy. The data generated throughout development and manufacturing must be accurate, consistent, and reliable to gain public trust and regulatory approval. Any discrepancies or inaccuracies in the data could lead to delays in manufacturing.
There is an increased sense of urgency to deliver high-quality drug products, including more and more advanced therapies, in as short a timeframe as possible. In particular, with advanced therapy medicinal products (ATMPs), the shelf life of products is extremely short, and accelerated release of products is needed to get therapies to the point of care fast enough. In these scenarios, even faster quality control testing is needed to manage risks.
Per the FDA’s Guidance Document, Data Integrity and Compliance with Drug CGMP, ensuring the accuracy and integrity of data is an important part of the industry’s responsibility to ensure the safety, efficacy, and quality of drugs, and of the FDA’s ability to protect public health. Data integrity findings during FDA inspections highlight gaps within the quality system and/or quality culture within an organization - demonstrating a breakdown in the prevention and correction of conditions that can lead to cGMP noncompliance.
Rapid Microbial Methods (RMMs)
Bioburden testing, environmental monitoring, and water testing are critical for contamination control, but traditional compendial methods can fall short of today’s need for speed and risk management. These tests are prone to human error and susceptible to gaps in data integrity. Data integrity concerns still remain with regard to subjective decision-making, lack of digital traceability, and a diminished interface with databases for actionable decisions. For manual tasks such as counting colonies in traditional bioburden methods, the “four eyes” principle is still relied upon to approve and report results and to try and prevent errors. Ambiguity in the QC lab is still very prevalent among analysts, so reducing the number of manual tasks and data transcription is crucial to put a microbiology lab in a proactive state rather than a reactive one.
RMMs provide quicker, more sensitive, and more accurate results compared to traditional methods. For example, the use of RMMs in the detection of microbial contamination in sterile and nonsterile pharmaceutical products has significantly reduced the time to result from several days to minutes.
Technologies such as flow cytometry are examples of RMMs that are transforming microbiology labs. Flow cytometry, for instance, is used to detect a population of cells or particles. This method is faster and more sensitive than traditional culture-based methods, enabling labs to detect contamination in a matter of hours rather than days. RMMs such as the Sievers Soleil can distinguish between viable cells and abiotic particles using proprietary fluorescent stains and high-throughput flow cytometry to ensure accuracy and sensitivity, obtaining near real-time bioburden data that correlates to plate counts.
The Integration of Data Integrity and RMMs
The integration of data integrity and RMMs in a modern microbiology lab offers numerous benefits. For example, the use of RMMs like flow cytometry, coupled with stringent data integrity measures, has enabled labs to provide accurate and reliable test results in a short span of time. This integration ensures that the data generated is not only fast but also reliable, thereby enhancing the efficiency and credibility of the lab.
As discussed in PDA’s Technical Report No. 80: Data Integrity Management System for Pharmaceutical Laboratories, “risks to ensuring data integrity might include computerized systems with lack of audit trails or appropriate security controls to prevent unauthorized changes as well as observational test methodologies.” With a high percentage of the tests conducted in microbiology laboratories being observational, risk factors can be reduced for the collection, control, and verification of microbiology data using RMMs that produce electronic records that are easily retrievable and tamper-proof. Obtaining digital results from an RMM reduces the chance of transcription errors being entered into a results repository, and using an RMM that adheres to 21 CFR Part 11 regulations will certify accuracy, integrity, and data security with an audit trail to provide a comprehensive record of actions taken.
However, implementing RMMs as part of a digital solution while being compliant with data integrity standards also presents challenges. These include the need for significant initial investment, training for lab personnel, and validation of the new methods to ensure they meet regulatory standards. Despite these challenges, the benefits of RMMs, such as increased efficiency and accuracy, make them a worthwhile investment for modern microbiology labs.
Regulatory bodies such as the FDA and EMA are increasingly emphasizing the importance of data integrity and the adoption of RMMs. This has led to the development of guidelines and regulations that ensure the accuracy and reliability of data, thereby promoting patient safety and trust in pharmaceutical products.
Data integrity and rapid micro methods are not just integral to the functioning of modern microbiology labs in the pharmaceutical industry but are also transforming the way they operate. By enhancing efficiency, and reliability, and ensuring patient safety and regulatory compliance, these elements are paving the way for a more advanced and reliable pharmaceutical industry. As the industry continues to evolve, the importance of data integrity and RMMs will only continue to grow.
Author Details
Tony Saavedra- Life Sciences Product Manager; Hayden Skalski - Lead Applications Specialist, Microbial Detection- Veolia Water Technologies & Solutions, Sievers Instruments
Tony Saavedra is the Life Sciences Product Manager at Veolia Water Technologies & Solutions, focusing on Sievers total organic carbon (TOC) software and instrumentation. Tony began his tenure with the Sievers product line as part of GE Analytical Instruments in 2011 in the field service organization and later held responsibility for leading the North America Technical Services team where he oversaw technical support, factory service, and refurbishment process operations. Prior to his positions with Sievers Products, Tony served for 10 years in the US Navy where he supervised flight inspections and performed quality assurance inspections and maintenance of complex electronic radar and communication suites. Tony holds a BS in Electronic Engineering Technology from ECPI University and an MBA from Colorado State University.
Hayden Skalski is the Lead Life Sciences Product Application Specialist for the Sievers Instruments product line at Veolia Water Technologies & Solutions, specializing in bacterial endotoxins testing (BET) and rapid microbial methods (RMMs). Hayden has over 8 years of experience in the pharmaceutical industry and Quality Control Microbiology and has presented on numerous topics surrounding endotoxin testing. Previously, Hayden held roles at CharlesRiver Laboratories, Regeneron, and Novartis, validating and executing method development protocols for endotoxin testing, providing customer support, troubleshooting, and supporting high-volume product testing. Hayden has a B.S. from the University of Albany (SUNY) in Biology.
Publication Details
This article appeared in American Pharmaceutical Review:Vol. 27, No. 2March 2024Pages: 40-41
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