Laboratory Information Management System (LIMS) in the Microbiology Lab

By: Paul Dudley

Today’s microbiology laboratories can generate an extensive amount of data across a variety of technologies.  Labs are tasked with providing  test results and information that is vital to the success of the organization and the safety of its products.   Of course, businesses and consumers demand efficiency – the goal is not only to provide safe products, but to provide them as quickly as possible.  As labs are updated and become more modern, better methods of data management and record keeping may be necessary in order to maintain or improve efficiency.  Luckily, there is a means to achieve this: Laboratory Information Management Systems, or LIMS. [1]

LIMS are software-based information systems that allows labs to track and share data within their environment.  There are numerous LIMS software applications, both open-source and proprietary.  But all have the same general goal – to help streamline data management to improve efficiency while reducing overhead costs.  LIMS can provide significant time savings for all people involved in a project by improving data access.  [3]

Example diagram showing the concept behind a Laboratory Information Management System and how data & information can be shared within a laboratory environment.

There are many advantages that the incorporation of a Laboratory Information Management System has over a more manual, traditional laboratory.  Some of these include improved efficiency, the ability to go paperless, cost reduction, and compliance.  Keep in mind, there are quite a few options when it comes to implementing a LIMS system, and whether it was initially an open-source application or a purchased program, a great deal of customization is usually implemented.  So when we talk about advantages, some may be more often utilized than others.  But any of these features can be of great benefit, depending on the wants and needs of the individual lab.

Efficiency

Improved efficiency is easily recognized when you eliminate the potential for errors from manual data entry.  The greater the amount of samples being processed and the total workload, the greater the chance for an error.  On the other hand, LIMS streamlines data entry by automating the process.  This results in less downtime, faster access to data, and the ability for the LIMS to grow with the increasing needs of the lab.

Paperless

Some LIMS programs will authorize users to either modify existing reports or create new ones.  Also, web-based applications can interface with the LIMS so users don’t need to work directly with the LIMS itself but rather can work with just the reporting modules that in turn query the database [5] .  QC Management can use LIMS for scheduling and Certificates of Analysis.  Another great ‘paperless’ feature of LIMS is the ability of some programs to hold all pricing information for tests, which allows invoices to be produced for online access or as PDF documents [5] .  There are many examples of projects for implementing a paperless lab and how they benefited their labs, and one example showed a 30-40% gain in resources as a result of going paperless [6] .

Cost Reduction

When it comes to management at an executive level, the proof is in the bottom line.  Successful businesses rely on effective cost management.  Total costs of operations come in many forms, including labor, resources, downtime, time-to-market,  and more.  LIMS can impact many of these costs of doing business.  For example, one laboratory that implemented a LIMS system reduced its capital investment by 50%, while productivity rose at multiple laboratories [3] .  Another lab saw a 50% increase in throughput two years after implementing their LIMS [7] .  When you consider the time savings, efficiency, and the resulting improvements in time-to-market, LIMS can significantly contribute to overall improvements in cost management.

Compliance

Product safety continues to be scrutinized in every market – including Food & Beverage, Nutraceutical, Cosmetics, and Pharmaceuticals.  Regulatory requirements are implemented to help reduce the risk of contamination, and different products and ingredients require different requirements.  This makes LIMS very essential.  LIMS can assist in real-time monitoring and Quality Control.  Workflows can be managed, samples logged, and tests can be checked against protocols and procedures to ensure compliance.  Out-of-spec samples can be reported automatically and flagged.   Reports can be automatically generated, and access to this information can be quickly gained by QC.  The overall increase in a structured approach via LIMS ensures compliance as business grows and throughput needs increase.

Neogen Corporation provides Rapid Microbiology Method (RMM) platforms such as BioLumix and Soleris.  Both systems can interface and exist within a LIMS environment.  For more information, visit http://www.mybiolumix.com or go to www.neogen.com.

The BioLumix system provides a single platform for all microbiology assays available for that system, allowing a large variety of tests without the need of additional equipment.  And its versatile – the modular design allows it to grow to meet throughput needs.   Results of tests for assays such as Total Aerobic Count, Yeast & Mold, Salmonella, and many more can be obtained within 24-48 hours.  Tests are be monitored in real time, and a Certificate of Analysis is automatically generated.  The system validates to USP <51>, <61>, <62>, <2021>, <2022>, and <2023> [9] .  In addition, Environmental Monitoring and Water Testing can be performed on the same platform.

Other advantages of the BioLumix System:

• Fully automated, easy to use.
• Faster sample preparation
• Faster turnaround time
• Fully Validated - the system comes complete with IQ, OQ, PQ and all SOP  documentation
• Outstanding support

As mentioned before, there are too many LIMS vendors to mention in this document.  Some applications will be better suited than others for your specific needs.  http://www.Limswiki.org has an extensive list of vendors that provide LIMS systems, and they even break out the vendors by industry.  So if you are looking for something more suited for Cosmetics, or for Food & Beverage, you can find those subcategories within that site.  It’s not the end-all be-all of resources, but it might be a good place to start.

SOURCES:
1. http://www.thermoscientific.com/content/tfs/en/products/lab-information-management-systems-lims.html
2. http://www0.cs.ucl.ac.uk/staff/B.Tagger/LimsPaper.pdf
3. http://khemia.com/clients/case-studies/
4. Ruth Eden, Ph. D., Neogen Corp.
5. Food Quality Magazine (http://www.foodquality.com/details/article/5621151/The_Paperless_Microbiology_Laboratory.html?tzcheck=1)
6. http://www.labmanager.com/laboratory-technology/2010/01/the-paperless-lab?fw1pk=2#.VIISO8mRJtY
7. http://www.labnews.co.uk/features/taking-lims-to-a-hire-level/
8. http://www.scientific-computing.com/features/feature.php?feature_id=246
9. http://www.mybiolumix.com/BioLumix-System-rapid-microbiological-methods

 

Water testing- Heterotrophic bacteria, coliforms and E. coli- Why and how to test

Water Quality

Water QualityWater is used in a variety of different industries as well as products within various industries, including Nutraceutical and Dietary Supplement, Pharmaceutical, cosmetics, toiletry industries.  Water can be used as a product ingredient, for example, to create the capsules that contain the supplement.  In the manufacture of the capsules many companies use their own water to create and encapsulate their products.   Water is also used for the cleaning of certain equipment and contact surfaces.

According to USP 1231, although there are no absolute microbial standards for water (other than water intended to be sterile), the CGMP regulations require the establishment of appropriate specifications. The specification must take into account the intended use of the water; i.e., water used to formulate a product should contain no organisms capable of growing in the product. Action or alert limits should be established based upon validation data and must be set low enough to signal significant changes from normal operating conditions.

Control of the microbiological quality of water is important for many of its uses. All packaged forms of water are required to be sterile because some of their intended uses require this for health and safety reasons. The needed microbial specification for a given bulk water depends upon its use. Some applications may require even more careful microbial control to avoid the proliferation of microorganisms ubiquitous to water during the purification, storage, and distribution.

To ensure adherence to certain minimal microbiological quality standards, water used in the production of drug substances or as source or feed water for the preparation of the various types of purified waters must meet the requirements of the National Primary Drinking Water Regulations (NPDWR) (40 CFR 141) issued by the U.S. Environmental Protection Agency (EPA) or the drinking water regulations of the European Union or Japan, or the WHO drinking water guidelines. Microbiological requirements of drinking water ensure the absence of coliforms, which, if determined to be of fecal origin, may indicate the potential presence of other potentially pathogenic microorganisms and viruses of fecal origin. Meeting these microbiological requirements does not rule out the presence of other microorganisms, which could be considered undesirable if found in a drug substance or formulated product.

USP<1115> deals with bioburden of non-sterile drug substances and products, and the chapter states that the biggest manufacturing risk is water as an ingredient.  Process water is the single most important risk factor contributing to the contamination of nonsterile products.  The purified waters that are used in manufacturing are deionized and do not contain chlorine that helps control microbial growth.  Purified water is capable of supporting growth of gram negative rod shaped bacteria and many different molds.

Water TestingThe FDA also covers a wide range of different types of water that can be used for pharmaceutical uses and describes different sources for water contamination.  The FDA even states that microbial contamination of oral liquids and topical drug products are a significant problem that is usually caused by contaminated water.  Due to the potential health risks involved with the use of contaminated water, particular attention should be paid to the deionized (DI) water systems, especially at smaller manufacturers.

Chlorinated water may be appropriate for early stage cleaning and sanitization activities, but the uses are risky and should only be used on a case by case basis.  Microbial enumeration is an integral component of a water monitoring system to assess the microbial quality of the water.  Some systems use both high-nutrient (PCA) and low-nutrient (R2A) media to allow the isolation of both heterotrophic organisms and slower growing oligotrophic bacteria.

Water testing is also important when dealing with well water, tap water and even bottled water.  The EPA uses coliform as an indicator of possible fecal contamination.  Coliforms naturally found in the environment, and are usually non-pathogenic, but their presence may indicate fecal coliforms.

The Rapid Automated BioLumix System

BioLumix SystemBioLumix automated; all-in-one microbial testing system is an ideal system for in plant water testing.  The system is fast, simple and cost-effective.  A novel optical system sensing color and fluorescence in ready-to-use vials provides faster results, labor savings, automation, and connectivity. The BioLumix system is capable of testing water for heterotrophic bacteria, total aerobic bacteria, E. coli, coliforms, fecal coliforms and yeast and molds. Using the BioLumix system will quickly determine the microbial quality of the water.

Heterotrophic Vial: This vial can detect organisms requiring low-nutrient media (similar to (R2A) to allow the isolation of both heterotrophic organisms and slower growing oligotrophic bacteria. In a study, over 50 samples of multiple different water types were tested by the BioLumix method and the plate count method side-by-side.  The BioLumix vials were directly inoculated with 0.1 mL of the water sample, or a 1.0 mL of a 1:100 dilution, and a few samples were inoculated with heterotrophic bacteria.  The samples were monitored in the BioLumix instrument for 35 hours.  The results showed that the BioLumix system was roughly 13 hours faster than the plate count method using Stand Methods Agar.  These particular samples were tested at specified levels <10 cfu/ml and <100cfu/ml, but the BioLumix method can detect organisms at levels of <1 cfu/ml of water.

Bottled water for human consumption also needs to be tested for coliforms, which are indicators of possible contamination. The FDA requires either MPN or membrane filtration to check 100 ml of water for any contamination. The MPN method which requires at least nine tubes to perform the test and up to 96 hours of testing; while BioLumix can do the same analysis using just one vial in less than quarter of the time.  The filter method can also be applied using the BioLumix system by filtering the 100ml onto a membrane filter and placing the filter directly into the vial.

What are the advantages of the BioLumix system?

The system serves, as a platform to perform all required assays- using the BioLumix system will allow the users to test for coliforms, heterotrophic bacteria, E. coli and Yeast/Mold. The system can be used for water testing as well as for testing raw materials, in process and finished products.

Saving time- The BioLumix system can save time when testing water for Heterotrophic bacteria instead of taking three days using traditional plates, the BioLumix system will give the same results in 35 hours.

Economical cost of assays: Instead of running an MPN assay, which will require up to 5 days of testing as well as 9 tubes of LTB and up to 9 tubes of EC Media to wait for confirmation of a positive fecal coliform, the BioLumix system requires less than 24 hours and a single vial.

References:

http://www.fda.gov/ICECI/Inspections/InspectionGuides/InspectionTechnicalGuides/ucm072925.htm -Water for Pharmaceutical Use

http://www.fda.gov/Food/FoodScienceResearch/LaboratoryMethods/ucm064948.htm  Enumeration of Escherichia coli and the Coliform Bacteria

USP <1115> Bioburden Control of Nonsterile Drug Substances and Products

USP <1231> Water Treatment Systems For Industrial & Commercial Use.

TIPS FOR SUCCESSFUL ENVIRONMENTAL MONITORING

Putting together an environmental monitoring plan requires a thoughtful, scientific approach establishing and considering the risks of contamination from each location along the manufacturing process.
environment monitor
WHY MONITOR THE ENVIRONMENT?

Environmental monitoring (EM) is a basic requirement across many regulated industries such as food, cosmetics, Nutraceutical, dietary supplements, and pharmaceuticals. It measures the degree of maintaining environmental control and, therefore, the safety of the manufactured products. Maintaining environmental control can prevent product contamination.

The FDA evaluates the environment of manufacturing facilities against the regulatory code, and the potential of the product allowing for growth of organisms. They expect manufacturers to be in control of the environmental conditions in their facility. There is evidence that a relationship exists between the level of environmental control and the final quality of the product. In product safety, the EM program serves a critical role that the environment is under appropriate control.

In manufacturing facilities, there is a need to demonstrate that production equipment is sufficiently clean thereby the next production lots are not contaminated from the material of the previous lot.

An effective sampling plan needs to be established, the purpose of a microbial EM program is to:
• Provide crucial information on the quality of the work process environment during manufacturing
• Prevent future microbial contamination by detecting and reacting to adverse trends
• Prevent the release of a potentially contaminated batch if the appropriate standards are not met
• Prevent the risk of contamination of the product
• Ensure there are environmental controls in the production areas
• Provide a profile of of the microbial cleanliness of the manufacturing environment.

SITE SELECTION FOR DATA COLLECTION

The site’s selection for data collection should show the effectiveness of cleaning. Such as:
• Site where the product is exposed to people and equipment
• Critical sites that can change product integrity if compromised
• Areas and processes steps where microbial contamination must not happen, such as the final filling of the product into its containers.

In establishing an EM plan, the number and location for sampling sites should be established. When choosing the sampling sites, there needs to be a good representation of risk-based sites where the environment can affect the product quality. Examples of such location include areas that are difficult to clean, or areas close to critical operations.

For sterile products, the manufacturer needs to keep the bioburden of the pre-sterilization as low as possible. There is a need to monitor the air, water, personnel, and surfaces as they all can contribute to the bioburden.
For non-sterile, low bioburden products, there are two main reasons for monitoring the environment:
1. To keep product bioburden under control
2. To know if the environmental isolates could contain objectionable organisms.

Other important questions to consider include:
? What is the antimicrobial effectiveness of the product?
? Will the product promote microbial growth?
? If so, which organisms can grow and get around the inhibitors build into the products?

ESTABLISH A BASELINE

Before initiating an EM program, it is recommended to get a baseline of total aerobic count, Yeast and mold count, perhaps coliform or Enterobacteriaceae, and in some instances lack of objectionable organisms on surfaces and the air. Establishing a baseline also allows for assessments of the types of organisms present, and helps in developing a scientifically sound disinfection program to address chemical kill and physical removal of such contaminants. The data subsequently collected during microbiological performance qualification, and routine monitoring helps to validate the efficacy of disinfection and cleaning procedures.

CHOOSE SUITABLE METHOD FOR EM

method for monitoring - swabsMost EM is done by plate counting of colonies on agar media, which is simple and inexpensive. However, plate count methods are slow, requiring two to seven days to complete, thereby causing a delay in the detection of contamination, which can lead to an increase in product loss, plant downtime and expensive cleanup. Delays can cause increasing inventory holding cost. The delay in obtaining results impacts reaction to contamination issues and can make investigations very difficult. The plate count methodology is also labor-intensive and requires manual data entry and documentation. Such documentation is prone to human errors and compliance issues.
Methods are available to measure total particles in the air, including Total Organic Carbon (TOC), and Adenosine Tri-phosphate (ATP).These methods are very fast to perform but do not correlate well with total bacterial count or any specific group of organisms, and do not measure viable organisms (Carricket al., 2001; Easter, 2010). Therefore, these results do not measure viable organisms in the environment or on production lines.

WHY BIOLUMIX

why BioLumixThe BioLumix system is useful for rapid and simple monitoring of the manufacturing environment. A large validation study was performed (Eden and Brideau 2012) to show that is correlates well with the plate count method. The BioLumix system was validated as an alternative to the plate count method for EM. The study involved 549 surface coupons representing five diverse types of material. These five surfaces represent those encountered in manufacturing, including metal, plastics and rubber. Some of the coupons were inoculated with bacteria, yeast, or mold. There was 100% agreement between BioLumix assay and the plate count assay for the 260 coupons that were determined to be below the specified level by the plate count method. There was an overall agreement of 97.2%between the two methods when swabs containing counts above the specified level were used. In general, discrepancies in swab results between the BioLumix vial method and the traditional plate count method reflected marginal samples that were very close to the specified testing level, and thus were variable.

REFERENCES

Carrick, K, Barney M, Navarro, A. and Ryder D. (2001). The Comparison of Four Bioluminometers and Their Swab Kits for Instant Hygiene Monitoring and Detection of Microorganisms in the Brewery. J. Institute of Brewing 107, 32-37
Easter M. (2010) A comparison of commercial ATP hygiene monitoring systems. Next Generation Food issue 9, 2010.
Eden, R. and Brideau, R. (2012). Validation of a Rapid System for Environmental Monitoring and Water Testing. In Environmental Monitoring Volume 6, Jeanne Moldenhauer, Ed