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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: 

• Method Suitability and Its Importance to the Test Method
• Sterility Test Failure: Possible Causes and Investigation
• Basics of Sterility Testing
• Submitting Samples for Sterility Testing
• An Inside Look at USP <71> Webinar
• An inside Look at USP <71> FAQ

A bulk substance, also known as an active pharmaceutical ingredient (API), is often the starting point of a compounded preparation.   Prior to use, compounding pharmacies and outsourcing facilities should confirm the quality of an active pharmaceutical ingredient to ensure consistency of the material as received from the supplier and suitability for use in a compounded preparation.  At a minimum, identity testing is recommended for each lot, but more rigorous testing should be evaluated.

Sterility testing by USP <71> is a test used in tandem with other sterility assurance procedures and tests to ensure that a product is free of microbial contaminants and safe for patients to use.  For a sterility test to perform appropriately, a method suitability validation must be completed on each specific formulation to determine the appropriate test method.

James Zellner, ARL Bio Pharma Technical Sales

How do you know your staff is doing a thorough job disinfecting surfaces and equipment at your facility?  Do you have proof that your cleaning procedure is effective in removing potential contaminants from surface areas?

Jessica Munson, M.S., ARL Bio Pharma Analytical Supervisor

What is a Master Formulation Record?

A Master Formulation Record is used to document the specific information for each individual batch and is an important component of regulatory compliance and effective process control. This detailed record of procedures describes how the drug product is to be prepared...

The Importance of Endotoxin Testing

Andrew Taylor, ARL Bio Pharma Microbiology Supervisor

In recent years, there have been instances of endotoxin-caused illness resulting from contaminated compounded sterile preparations. In 2015, an incident occurred where seven cases of endotoxin poisoning were related to contaminated glutathione infusions.

Pharmacists often want to assign a beyond-use date (BUD) on a drug product longer than USP guidelines to increase compounding efficiencies and reduce drug waste. For accurate BUD assignment, Stability-indicating methods are recommended as opposed to Potency methods. Stability-indicating methods are specifically designed to separate drug degradants from non-degraded drug (for more information about the difference between the two methods, see Stability vs. Potency testing article).

ARL now offers USP <1207> container closure integrity testing (CCIT) on IV bags, syringes, and vials.

Three types of leaks that can be detected during CCIT include:  

• entry of microorganisms
• escape of the product dosage form or entry of liquids or solids
• escape of nitrogen gas or entry of oxygen, water vapor, or air gases

James Zellner, Technical Sales

Identification of a contaminant in a sterile preparation is vital to determining the origin of the microorganism and its avenue of entry.  The organism’s identity, combined with environmental monitoring data, provides actionable information to improve a pharmacy’s processes and prevent future contamination.