The BioSciences Quality Testing Forum website recently consulted its regular members about their experiences and best practices in microbial identification. (Full results can be found on www.BioQTForum.com.) While the number of participants in the survey was modest—around 50, with about half from pharma, one-fifth from biotech, and the rest from cosmetics and other industries—the data provides an interesting sketch of current microbial ID practices.
We took the opportunity to query consultant and survey lead Pascal Yvon, PharmD, MBA, about the implications of the results. Dr. Yvon has over 20 years of experience working with international diagnostics, pharmaceutical, bio-technology, and cosmetics companies, and is a frequent speaker and author on current microbiological topics.
PhM: Is there any surprise here? What explains the popularity of species level ID?
P.Y.: The majority of respondents (72.4%) use at least the genus level to address situations encountered within the manufacturing environment. Most labs use the species level as it provides the information details that most situations require and satisfies regulatory requirements such as the FDA aseptic processing guidelines. A significant number of labs report Gram stain as primary level and it is a bit surprising, as it provides limited ID information (it may not be their final step). Caution may be necessary with the Gram stain as a reportable result. There is inherent variability in the test and many of the organisms encountered in a manufacturing environment can be in a growth state that will not provide consistent Gram stains.
Question: What method(s) do you use as reportable microbial ID?
PhM: Again, could you interpret these numbers? What do you read in them?
P.Y.: Microbiologists use different identification techniques depending on their needs, and take into account the time to results and testing costs. Most companies use phenotypic methods and reserve genotypic methods for very specific situations (sterility test failures, environmental monitoring excursion exceeding established action levels). The former methods are well established with extensive databases (it is important to check their relevance for the biopharma QC labs). The latter techniques present advantages but are more expensive (capital investment, validation, cost per test) and are more technically challenging. Despite those limitations, a significant number of companies use genotypic methods.
PhM: Would you consider these encouraging data? What presumptions can you make about manufacturers that are reporting more than 2,500 ID’s per year?
P.Y.: The data show the diversity and range of workload that can be found. Most companies (nearly 80%) perform less than 1,000 reportable ID tests per year, with 41.4% performing less than 100 per year. The numbers of identifications performed does not necessarily show an organization’s environment out of control, as numbers can often increase upon qualification of a new manufacturing suite, monitoring of new personnel, qualification of a new ingredient supplier, etc.
PhM: Do you expect these numbers to continue to improve as manufacturers seek ways to accelerate their time to results?
P.Y.: Yes, time to results is important for manufacturing companies (see next question) and they spend time and effort to improve it. Vendors also keep developing rapid microbial identification methods and solutions to provide a faster turnaround time: MALDI-TOF (absence of sample preparation, rapid analysis, high throughput) and genetic sequencing methods do not require large amounts of cellular mass and can be performed routinely in hours from when an initial colony is seen, multi-angle laser light scattering, etc. An important consideration is the number of genera and species in the database and its relevance to the concerned industry and its environment.
PhM: What does this tell us about what microbiologists want or need?
P.Y.: Beside the legitimate request for accurate and reliable methods, microbiologists expressed what they want: cheaper, faster, less labor intensive (more automated, outsourced), ideally all at the same time!