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USP <61> and USP <62> Microbial Tests for...

USP <795> states compounders are responsible for ensuring compounded drug products are of acceptable strength, quality, and purity. The chapter also directs compounders to USP <1163> for recommended quality control procedures.

USP <1163> specifies the appropriate microbiological tests of non-sterile products:

  • USP <61> Microbial Enumeration Tests

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COVID-19 Industry News and Resources

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  • Pharmacy Associations
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Importance of Sample Amounts...

This article outlines the importance of sample amounts submitted for potency testing and the impact it can have on potency results. Formulations require different sample amounts to allow for an accurate result representative of the compounded preparation. The table below can also be found in ARL's Sample Submission Guidelines

USP <51> Antimicrobial Effectiveness Testing

Antimicrobial Preservatives are excipients added to multi-dose containers for both sterile and nonsterile drug products. These preservatives are used to prevent growth of microbial contamination occurring during the use period. It's important to note that antimicrobial preservatives are not a substitute for good manufacturing practices. 

The USP <51> Antimicrobial Effectiveness Test is a challenge test for aqueous-based products. This test demonstrates the effectiveness of antimicrobial preservatives in preventing proliferation or limiting microbial contamination. It is performed on injections, topicals, oral products, and antacids packaged in multiple-dose containers. Click here to access a table of Common Pharmaceutical Preservatives.

An Update regarding COVID-19

ARL Bio Pharma is prepared and has taken steps to ensure our lab continues to provide testing services during this unprecedented time in the United States. We are taking every precaution to follow CDC guidelines and state and federal mandates regarding COVID-19.

Our laboratory is committed to our responsibility as a business partner in the drug supply chain to keep our clients up and running during this health crisis. To deliver the best technical service, we are available to support you Monday through Friday 7:30 a.m. to 6:00 p.m. CST at 800-393-1595 or 405-271-1144.

ARL is dedicated to assuring the health and safety of our employees, our customers, and the communities we serve. Our laboratory is working with our department and logistic partners to ensure supplies capacity in and out of our laboratory and are continuing to fulfill testing services. We will keep you informed of any impact on our ability to meet turnaround times and expectations.

Please follow the CDC website for the latest updates on COVID-19; and, ARL's website and online portal for service updates.

Thank you for your business and continued confidence in ARL to support your needs.

ARL Bio Pharma

Growth Media Differences

There are dozens of different types of microbial growth media available to Microbiologists, developed for a wide variety of purposes.  The USP references many of these to demonstrate the quality of both compounded drug products and the control of compounding environments.  The various types of media serve specific purposes based on the goal of the test.  This might include recovery of the broadest range possible of organisms in a sterility test, screening for a specific organism if it would be particularly dangerous in a certain dosage form, or capturing anything that might be in the compounding environment that might find its way into finished product.  Microbial growth media can be prepared in both liquid and solid forms, depending on the application.  Tryptic Soy Agar (TSA) and Tryptic Soy Broth (TSB), for example, have the same nutrient profile and similar ingredients, but TSA is a solid and TSB is a liquid.  For conducting passive air sampling, for example, a solid TSA plate is easier to handle and leave out in the hood during compounding.  Liquid media, like TSB, is generally better at growing organisms, and should be used where possible for recovery of microorganism in drug products.  Liquid media is more conducive to growth, since nutrients, oxygen, and waste products move around more freely, and temperature is more uniform and constant in a fluid.

Rapid Sterility Testing

Rapid sterility testing is an alternative test method to USP Chapter <71>, which allows for shortened incubation times compared to the traditional sterility testing method. Where USP <71> requires between 14 and 18 days of incubation before a final test result, a rapid sterility test result can be generated after only 6 days of incubation. A reduction in test time of between 8 and 12 days offers a significant benefit when considering supply chain issues, product release schedules, and the timeliness of contamination investigations. The shortened incubation time is made possible by utilizing advanced technology designed to detect microbial growth much more quickly than visualized by the human eye.

USP <800> Why should you test?

As a compounder, protecting yourself and your staff from exposure to hazardous drugs should be important both from a safety and monetary perspective.  USP <800> applies to sterile and non-sterile compounding pharmacies and anywhere that hazardous drugs are received, stored, or administered.   It is also designed to prevent compounders from incurring fines from OSHA (Occupational Safety and Health Administration) for not providing a safe workspace and not complying with the information in USP <800> or on the NIOSH list.  Compliance with regulations includes having: a negative pressure lab to compound hazardous drugs, the appropriate design, layout, or equipment in the pharmacy to compound these materials, and appropriate controls for handling finished dosage forms.  If a facility is compounding or handling hazardous drugs in a state not enforcing USP <800> but is shipping to a state that is, they must comply.  Even if a state board of pharmacy has chosen not to adopt USP <800>, OSHA is still the regulating agency and can inspect a facility that handles or compounds hazardous drugs and levy a fine if they do not comply.

Open vs Closed Membrane Filtration...

According to USP <71> Sterility Tests, membrane filtration is the sterility test method of choice for filterable pharmaceutical products. Membrane filtration refers to either an open membrane filtration (OMF) or closed membrane filtration system. Not all sterility test systems are the same. It is important pharmacists know the differences between the two systems to reduce the risk of false positive results, costly investigations, and batch loss.

USP <71> Sterility Testing

USP <71> Sterility Tests is a general chapter enforceable by regulatory agencies and is applied to substances, preparations, and articles required to be sterile. This chapter demonstrates process control and is a general indicator of the microbiological quality of a product. It's important to note that the <71> "pharmacopeial procedures are not by themselves designed to ensure that a product or batch is sterile or has been sterilized. This is accomplished primarily by validation of the sterilization process or of the aseptic processing procedures." For ARL to list USP <71> as the test method, pharmacists must certify and submit the correct number of articles in accordance with Table 3 in the chapter.

A sterility test is performed under aseptic conditions. Precautions are taken to avoid contamination, so the testing environment does not impact any microorganisms that are to be revealed during the test. ARL Bio Pharma regularly monitors working test conditions by appropriate environmental sampling of the work area and carrying out suitable controls.  

ARL Sterility Test Process: 

  • ARL performs growth promotion testing and assesses other quality parameters to confirm that each lot of ARL's media can support growth of the six microorganisms stated in USP <71> Sterility Tests.
  • Prior to conducting a USP <71> sterility test, our laboratory performs method suitability for each specific product formulation to ensure that an appropriate method is chosen for testing.  
  • During performance of a sterility test, ARL uses either a closed membrane filtration method (the preferred method, when possible) or a direct inoculation method for unfilterable sample types. To ensure that a sterility test is USP <71> compliant, ARL tests the correct sample volume according to Table 2 in the chapter. The test containers are then incubated at the appropriate temperatures for at least 14 days. 
  • At the end of the incubation period, each test is examined for signs of microbial growth, which generally present as turbidity or cloudiness of the media.

At the conclusion of the test, if there is no evidence of growth, the drug product complies with the USP <71> test for sterility. A "Sterile" result indicates that no contaminating microorganism is found in the sample examined under the conditions of the test.

If the test reveals signs of contamination, the drug product is considered "Not Sterile" and an OOS investigation will be initiated.

For more information on Sterility Testing, visit the articles and webinar below: