CBE Pure Solutions introduces Australia’s first Sterility Rapid Microbiology Methodology (SRMM) utilising world recognised BioMérieux Scan RDI platform
This groundbreaking method reduces sterility testing times from 14 days to <6 hours, reduces inventory hold times and significantly improves microbiological quality control.
Onshoring Innovation: Sterility Rapid Microbiology Methodology
By Riley Fitzpatrick and Kirsty Bates, Senior Microbiologists - CBE Pure Solutions
Article highlighted in the April issue of the Australasian Biotechnology Journal (pages 22-24)
The introduction of bioMérieux's SCANRDI® rapid sterility test in Australia by CBE Pure Solutions (CBEPS) marks a significant advancement in the Australian pharmaceutical and biotechnology sectors, offering a swift and reliable method for detecting microbial contaminants. This technology addresses the critical need for rapid sterility testing, ensuring patient safety and enhancing operational efficiency within the industry.
Image: Riley Fitzpatrick, Senior Microbiologist - CBE Pure Solutions
Compendial Sterility testing has traditionally been performed according to the European Pharmacopeia (Ph. Eur) chapter 2.6.1 and United States Pharmacopeia (USP) chapter <71>, which requires a 14-day incubation period in growth media to allow any contaminants to grow, during and after the test samples are inspected visually. The compendial sterility test is a presence-absence test in which the turbidity of the culture media is indicative of microbial growth and verified by visual inspection. The culture media used in sterility testing are fluid thioglycolate medium (FTM) and soybean-casein digest medium (SCDM). FTM is used to detect aerobic and anaerobic microorganisms, and SCDM is used to detect aerobic bacteria and fungi. These long incubation periods result in subsequent delays to process understanding and product release, particularly for time-sensitive products like advanced therapy medicinal products (ATMPs), or short shelf-life products.
Sterility Rapid Microbiology Methodology (SRMM) established by CBEPS utilising bioMérieux’s world-leading technology SCANRDI® platform [1] has revolutionised rapid microbial detection by delivering actionable sterility results in four hours. Its unique technology combines universal cell labelling with solid-phase cytometry, enabling the detection of bacteria, yeasts, and moulds, both in vegetative and sporulated forms. This rapid detection capability allows manufacturers to make faster decisions regarding production processes, thereby minimising downtime and reducing the risk of distributing contaminated products.
SRMM using the SCANRDI® Instrument System has four (4) basic operational steps:
1. Product filtration
2. Labelling of microorganisms
3. Laser scanning
4. Verification of events detected
Liquid samples are taken and aseptically filtered through a specialised 0.4µm pore track-etched membrane. Microbes retained on the membrane filter are then directly labelled in situ with fluorescent viability markers which enters the microorganism through the cell membrane. Living cells cleave the non-fluorescent viability substrate by an enzymatic reaction, releasing fluorescent particles (free fluorochrome) within the cell.
The prepared membrane is transferred to the SCANRDI® where laser excitation of fluorescent dye occurs (solid phase laser cytometry). The entire surface of the membrane is laser-scanned, and the accompanying software analyses the resulting data. The SCANRDI® System’s laser scanning capabilities ensure that any cell fluorescence on the membrane will be detected by the system’s multiple detection channels. Nonliving cells are not metabolically active and are not labelled.
To ensure reliable results, the system incorporates advanced proprietary discrimination parameters which allows the system to differentiate between labelled microorganisms and background “noise” (electronic, optical, and auto-fluorescence from particles). The data is represented as an event map which displays the location of each detected event. These stained microbes are then detected by an image analyser, and their presence is confirmed microscopically by a trained microbiologist. The whole process is completed within hours.
Image showing Microscope assessment using Scan RDI
Riley Fitzpatrick, Senior Microbiologist - CBE Pure Solutions
Regulatory acceptance of rapid microbiological methods (RMMs) like SCANRDI® is supported by major regulatory bodies, including the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) and the Therapeutic Goods Administration (TGA). These agencies acknowledge that validated RMMs can be equivalent or superior to traditional methods, especially for products with short shelf lives where timely results are crucial. Implementing SRMM aligns with regulatory expectations and demonstrates a commitment to adopting innovative technologies that enhance product safety and quality.
The TGA utilises relevant sections in the Ph. Eur. and British Pharmacopoeia (BP) in that these compendia also allow for the validation of alternate methods. They also rely on the validation guidance from USP Chapter <1223>, Ph. Eur. Chapter 5.1.6, PDA Technical Report #33, and ISO 17025 (validation of non-standard methods).
Performance Qualification (PQ) of RMM for the Australian pharmaceutical landscape requires meticulous planning to ensure compliance with regulatory standards. CBEPS has performed extensive Design Qualification, Instrument Qualification and Operational Qualification which also includes demonstrating equivalence or superiority to compendial sterility testing [2]. For qualitative SRMM testing, qualification addressed specificity, sensitivity, ruggedness, robustness, and equivalence. For quantitative testing, accuracy, precision, ruggedness, robustness, equivalence, sensitivity, linearity, and specificity were demonstrated.
CBEPS has developed a PQ package that will support clients on their product specific needs to deliver a simplified validation process to provide a comprehensive data package, including all the necessary cGMP testing protocols.
Advantages associated with the adoption of CBEPS SRMM to Australian pharmaceutical and biotechnology manufacturers include:
1. Accelerated Product Release: Rapid detection of microbial contaminants enables quicker product release, which is particularly beneficial for products with limited shelf lives or those requiring immediate availability
2. Enhanced Process Control: The ability to obtain early notification of positive results allows for real-time monitoring of manufacturing processes, facilitating prompt root cause investigations and corrective actions when necessary and reducing the risk of large-scale contamination and prevent long shut down of filling lines
3. Operational Efficiency: By reducing the time required for sterility testing, SRMM helps streamline production schedules, optimise inventory management, and improve overall supply chain efficiency
4. Regulatory Compliance: Utilising a qualified and validated rapid sterility test method aligns with international regulatory guidelines, supporting compliance and potentially expediting approvals for new products
5. Automated results: SRMM using the SCANRDI® Instrument System provides automated readouts, reduced subjectivity and reduced human errors
CBEPS establishment and deployment of bioMérieux's SCANRDI® rapid sterility test in Australia represents a pivotal advancement in microbial detection technology. By offering expedited and reliable sterility testing (within 1-2 days), SRMM addresses critical challenges faced by the pharmaceutical and biotechnology sectors, including the need for faster product release and enhanced process control. While implementation requires careful consideration of qualification, training, and integration aspects, the potential benefits in terms of operational efficiency and regulatory compliance are substantial. As the industry continues to evolve, embracing innovative technologies like SRMM will be essential to meet the growing demands for safe and effective pharmaceutical and biotech products.
References:
1. www.Biomerieux-industry.com
2. Deutschmann S. et.al. Rapid Sterility Test Systems in the Pharmaceutical Industry: Applying a Structured Approach to their Evaluation, Validation and Global Implementation. PDA Journal of Pharmaceutical Science and Technology January 2023