On May 1, 2009 the United States Pharmacopeia (USP) General Microbiology chapters will be harmonized with corresponding microbiology chapters in the European and Japanese Pharmacopeias (EP and JP). The goal of pharmacopeial harmonization is to promote consistency of microbiology methods used by companies globally. This harmonization includes revisions to the existing USP <61> Microbial Limits Test that creates two new chapters: USP <61> Microbial Enumeration and USP <62> Absence of Specified Organisms. Celsis International plc (LSE: CEL.L) - a leading global provider of innovative life science products and laboratory services to the pharmaceutical, biopharmaceutical, and consumer products industries - outlines the key steps the pharmaceutical industry should take to ensure they are ready to address these harmonization changes.

Key Steps to Prepare for Harmonization Changes

Following are the top steps companies in the pharmaceutical industry should take to ensure they are prepared for changes to the General Microbiology chapters USP <61>: Microbial Limits Testing and the addition of USP <62>: Absence of Specified Organisms.

1. Understand that changes to the USP will not affect alternate microbial test methods, such as Rapid Methods. Rapid Microbial Methods (RMMs), such as those provided by Celsis, are accepted microbiology tests that can be used in lieu of the tests as defined in the USP Microbiology Chapters. Those who have implemented such alternate methods are unaffected by the changes to the USP.

2. Understand how the new chapters impact the requirements for growth and recovery of specified microorganisms and specified microorganisms tests. In USP <61> (formerly called the Microbial Limits Test, now renamed the Microbial Enumeration Test), the most obvious change is the separation of the Absence of Specified Microorganisms test into a new chapter, USP <62>. USP <62> is a new chapter that describes the requirements for growth and recovery of specified microorganisms such as Salmonella or S. aureus. Important to note is that all of the specified microorganism tests have undergone changes. Also, media for enrichment, subculture and selection have changed for most microorganisms.

3. Find out how the changes apply to inventory that was validated with current (prior to May 2009) standards. Based on changes in these harmonized chapters, products may need to be revalidated. Reasons include, but are not limited to, media requirements, testing conditions and the amount of sample to be used. For example, if you are using the USP method and want to continue to use it but the media has changed, you will need to revalidate using the new media. Companies should also consider the possibility of a sample that previously used a specified dilution not being acceptable at that same dilution with the newly specified media.

4. Know how changes to USP <61> will alter sample amounts for bulk vs. small batches.Depending on the test or combination of tests, the sample amounts to be required may vary. As per harmonized USP <61> in the section covering testing of products, the amount used for the test should be 10g or 10mL. For fluids or solids in aerosol form, it is necessary to test 10 containers. For transdermal patches, 10 patches are to be tested. Additional information to justify using less product is provided in the harmonized chapters; examples include small dosage units, small batch sizes or limited number of articles in a batch.

5. Determine when and how often to test (i.e. at which stages within the production process - from raw materials to finished goods). Given the number of changes to USP <61> and the addition of USP <62>, it's important to plan ahead not only for the type of analysis to be performed, but for the time and cost required to do so effectively. Should the analysis not meet the initial requirements, additional testing may be necessary which could require extra time. Be sure to build enough flexibility into your schedule to accommodate these scenarios, and consider using rapid microbial screening methods. Absence of contamination can be determined in 18-24 hours (vs. an average of five days), significantly reducing production cycle times.

6. If you outsource to an analytical lab, evaluate how this contract facility is meeting the new requirements of USP <61> and the addition of USP <62>. Since significant changes are a result of harmonization with EP methods, contract labs with global customers typically have already screened products to the new USP and EP chapters, giving them a head start. Many contract testing labs such as Celsis Analytical Services offer validation services in addition to routine analysis to ensure that testing is in compliance with the new harmonized requirements. Make sure that your lab partner stays abreast of changes in the USP so you can be confident that their services are performed according to current pharmacopeial requirements.

7. If you currently have internal testing methods to screen for contamination and to enumerate specific organisms, consider how you will need to reconcile your current methods with the USP guidelines. Given the significant changes to USP <61>, if you have your own methods for testing microbial limits, you need to ensure that they are fully validated and adhere to updated methods. Remember that the new USP methods are now more inclusive for more organisms, which can have an impact on microbiological media used in testing for specific pathogens, incubation temperatures and duration times.

8. Recognize how changes to USP <61> and <62> prohibit retesting and determine how this will impact your operations. Under the new USP chapter guidelines, retesting of an original sample is not allowed. However, it is acceptable to perform additional analysis on a sample that screens positive for contamination using a rapid method. For this reason, non-destructive rapid testing methods are preferred. When contamination is found, the use of rapid methods adds additional savings in time-to-corrective-action and time-to-market of a replacement lot.

9. Familiarize yourself with the additional organisms that have been specified in the new USP <62>. It's important to note that more organisms have been specified in the new USP <62> chapter than in previous USP editions. Organisms such as Candida albicans, Clostridia species, and bile-tolerant Gram-negative bacteria may be necessary to test for, depending on specific product formulation and utilization.

10. Recognize how changes to USP <61> and USP <62> alter incubation times. USP <61> describes microbial enumeration tests, which are the plate count procedures for bacteria, yeast and mould. Although the plate count procedure itself will not change, the incubation temperatures and times for bacteria do change slightly. In USP <62>, tests for specified microorganisms are included. Not only do new modifications change many microbiological media utilized in testing for specific pathogens, but updates also affect incubation temperatures and duration.

11. Understand how updated methodology of the Method Suitability Test in USP <61> and USP <62> impact the types of organisms and different growth media that are included. The Method Suitability Test replaces the Preparatory Test for product inhibition. Both the growth-promotion organisms and the methodology have been significantly updated to include more types of organisms and different growth media. Companies are strongly encouraged to revalidate products to conform to the new USP <61> and <62> Suitability Test, and they must now specify which microorganisms are required to be absent. The Suitability Test ensures that any antimicrobial activity inherent in the test sample will not adversely affect the reliability of the test. It also validates that the test procedure is suitable for use with a given sample.

12. Understand that the specified organisms in USP < 61> and USP <62> may not be all inclusive. The organisms listed in USP <61> and USP <62> are example organisms. Each user should also consider testing for organisms that are specific to their facility or to their products.

For More Information
Download the Celsis White Paper Concerning Changes to USP <61> and the Addition of USP <62> online at