Wednesday, July 28, 2010
Tuesday, July 20, 2010
bioQTForum (http://bioQTForum) has posted a new article on their website entitled "Evaluating Library Databases for Microbial ID - Critical Aspects and Recommendations.” The key focus of this review is to present questions to ask manufacturers and contract laboratory services about their microbial identification libraries and analytical tools used for microbial identifications. The article discusses the attributes and limitations of different methodologies in analyzing results to determine an ID. Equally important in a highly regulated industry, cGMP, compliance and validation strategies for library database entries and maintenance are explored. I have also added a link to the article on our RMM References Page (http://rapidmicromethods.com/files/references.html).
Monday, July 19, 2010
Thursday, July 15, 2010
Alcon has published their second paper on using a RMM for sterility testing. This time they focus on how to compare the limit of detection between the RMM and the pharmacopoeial method. The reference and abstract are below:
2010. Ron Smith, Mark von Tress, Cheyenne Tubb and Erwin Vanhaecke. Evaluation of the ScanRDI as a Rapid Alternative to the Pharmacopoeial Sterility Test Method: Comparison of the Limits of Detection. PDA J Pharm Sci Technol. 64: 211-221.
Two sterility test methods, the ScanRDI_ rapid sterility test and the United States Pharmacopeia/European Pharmacopoeia/Japanese Pharmacopoeia (USP/EP/JP) compendial sterility test, were compared with respect to the limits of detection for the presence of viable microorganisms in aqueous solutions at low inoculation levels. The ScanRDI_ system employs a combination of direct fluorescent labeling techniques and solid-phase laser scanning cytometry to rapidly enumerate viable microorganisms from aqueous samples, whereas the compendial sterility test is a qualitative, growth-based method that uses a visual assessment of turbidity to indicate microbial contamination. Eight microorganisms were evaluated, seven compendial microorganisms (Clostridium sporogenes, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Aspergillus niger, Candida albicans) and the Gram-positive anaerobe Propionibacterium acnes. The number of viable organisms was estimated using the ScanRDI_ method and the conventional sterility test method using most probable number methodology. The mean difference between the methods was computed and 95% confidence intervals around the mean difference were estimated. The ScanRDI_ method was found to be numerically superior and statistically non-inferior to the compendial (USP/EP/JP) sterility test with respect to the limits of detection for all organisms tested.
Tuesday, July 13, 2010
More industry users of rapid methods are publishing their assessment and validation studies in scientific journals. In the May-June issue of the PDA Journal of Pharmaceutical Science and Technology, two excellent papers were presented on endotoxin and sterility testing. Their references and abstracts are below.
2010. Luis Jimenez, Narendra Rana, Kasey Travers, Verce Tolomanoska, and Kimberly Walker. Evaluation of the Endosafe® Portable Testing System™ for the Rapid Analysis of Biopharmaceutical Samples. PDA J Pharm Sci Technol. 64:211-221.
The Endosafe® Portable Testing System™ (PTS™) portable system for endotoxin testing was evaluated to analyze biopharmaceutical samples such as raw materials and finished products. The installation, operational, and performance qualification procedures were successfully implemented and verified to determine the system functionality under good manufacturing practices. During the validation stages the PTS™ was compared to the gel-clot test method in terms of presence or absence of endotoxin substances, ease of use, completion time, resource optimization, and sample volume. Water for injection and product samples were analyzed with both methods. All water for injection and product samples were negative for the presence of endotoxin by both methods. However, PTS™ results were obtained after 15 min while the gel-clot completion time was 1 h. Miniaturization of endotoxin testing by the PTS™ allowed optimization of testing procedures by reducing sample volume, analyst manipulations, accessory materials, and turnover time, and by minimizing the risk of exogenous contamination of the reaction.
2010. Jennifer Claire Gray, Alexandra Staerk, Manfred Berchtold, Werner Hecker, Gunther Neuhaus, Andreas Wirth. Growth-promoting Properties of Different Solid Nutrient Media Evaluated with Stressed and Unstressed Micro-organisms: Prestudy for the Validation of a Rapid Sterility Test. PDA J Pharm Sci Technol. 64:249-263.
Currently, sterility testing in the pharmaceutical industry—a mandatory release test for all sterile drug products—takes an incubation time of at least 14 days and is based on liquid media according to the pharmacopoeias. The search is on for a rapid sterility test to reduce this rather long time frame. For this we have chosen the Millipore Milliflex Rapid Microbiology Detection System, which is based on solid nutrient media. As a prerequisite for the validation of this rapid sterility test, a solid nutrient medium promoting the growth of stressed and unstressed micro-organisms replacing tryptic soy broth and fluid thioglycollate medium from the traditional sterility test had to be found.
For this a wide variety of appropriate nutrient media were evaluated. After a prestudy with 10 different nutrient agar media, tryptic soy agar, Center for Disease Control (CDC) anaerobic blood agar, Schaedler blood agar, and Difco brewer anaerobic agar were tested in detail using a range of 22 micro-organisms (7 ATCC strains and 15 production site-specific strains). These strains were inoculated in their unstressed and in a stressed state. Stress was evoked by heat treatment and nutrient starvation in the case of the sporulating bacteria. This stress effect—resulting in deceleration in growth—was experimentally confirmed based on growth curve analysis. It was statistically evaluated which media and which incubation temperatures are best suitable.
The resulting data showed that Schaedler blood agar has the best growth-promoting properties among the agars tested and is going to be used in the rapid sterility test with the incubation temperatures 20–25 °C for aerobes, 30–35 °C for aerobes, and also 30–35 °C for anaerobic micro-organisms.
Friday, July 9, 2010
Two new rapid method articles have appeared in this month's American Pharmaceutical Review. Links to both online articles may be found on our Reference Page (http://rapidmicromethods.com/files/references.html). Here are the references:
2010. Denoya, C.; Sessions, D.; Shabushnig, J. A Rapid Microbiological Assay to Monitor the Effectiveness of a Vaccine Injector Sanitization Following a Microbial Challenge Procedure. American Pharmaceutical Review. 13(4): 54-61.
2010. Duguid, J. Top Ten Validation Considerations When Implementing a Rapid Mycoplasma Test. American Pharmaceutical Review. 13(4): 26-31.