Editorial: Quality Assurance in Compounding, Part XII

United States Pharmacopeia (USP) Chapter <71> Sterility Tests

Does a sterility test ensure sterility of a manufactured product or compounded preparation? The answer is "no." From USP Chapter <71>, "These Pharmacopeial procedures are not by themselves designed to ensure that a batch of product is sterile or has been sterilized. This is accomplished primarily by validation of the sterilization process or of the aseptic processing procedures."

The results of potency testing for solid and liquid dosage forms should be representative of the entire batch of product/preparation. This testing can be conducted either in-process (as is the trend) or on the final product/preparation. However, sterility testing is done on the final product/preparation and is only an indication that the tested unit is sterile or nonsterile. The only way to be ensured that the entire batch is sterile is to test each and every unit. Sterility is basically assured at the level of only 1 in 1,000,000 (10⁶) being contaminated. So, it is not an absolute quality check.

If a vial used for testing contains only one microorganism (nonsterile) and the quantity used (according to Tables 2 and 3 in Chapter <71>) is less than the container, it is possible that the microorganism may not be in the portion transferred to the media; consequently a "sterile" result may result from a "nonsterile" preparation. If a batch of 30 vials was processed and there was only one microorganism in one of the vials and the test requires 10% or 4 containers, whichever is greater, then there is a good likelihood that the vial containing the microorganism may not be selected for the test and a result of "sterile" would be returned when one vial is nonsterile. This is true of manufactured products as well as compounded preparations.

Sterility testing is more of a "process" control procedure to determine if all the activities and materials utilized together result in a "sterile" product/preparation. A "nonsterile" result may occur due to problems in the manufacturing/compounding procedures or due to improper laboratory technique. Both the laboratory and manufacturer/pharmacy should investigate to determine the source of the problem.

As we are all aware, recalls due to nonsterile products in the market place do occur; however, the clinical results can be devastating. As we would certainly not want any manufacturer to produce sterile products without sterility testing, compounding pharmacies should not compound sterile preparations without a sterility testing program in place. If outsourced, a qualified laboratory should be used; if done in-house, the method needs to be verified and routinely checked.



Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief

If you are not a current subscriber to the International Journal of Pharmaceutical Compounding, look at what you are missing!

1. A new series on the practical implementation of USP Chapter <797>
2. Articles explaining the complete process used for revising USP Chapter <797>
3. The intriguing history of Premarin, involving some behind-the-scenes activities and unfair practices
4. The politics of human hormones (bioidentical hormones)
5. Responses to national organizations that formerly downplayed bioidentical hormones but now seem to support them

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This Regulatory Update has been provided by the International Academy of Compounding Pharmacists (IACP). For more information, www.iacprx.org.

Plan on joining hundreds of compounders in Washington, DC for IACP's Compounders on Capitol Hill July 7-10. Your presence is important! See www.iacprx.org/site/PageServer?pagename=Annual_Meeting for more information and to register today.

Hormone Confusion
Due to all the confusion and misrepresentation by many individuals and organizations related to the use of the word "bioidentical," maybe we should consider using the term "human hormones" instead! We already have "human insulin," so why not have "human hormones," including "human estradiol," "human estrone," "human estriol," "human progesterone," "human testosterone," and others?

The word "natural" is confusing as many think that the "human hormones" come from natural sources. True, the starting point may be yam or soy, but that is only as a source of the chemical nucleus to chemically synthesize the individual human hormones; nothing of the yam or soy should be present in the final USP-grade material.

One last thing, as a comparison with insulin, insulin begins as a product from two different strains of E. coli, where it is then chemically modified to form human insulin. A pretty good analogy with human hormones; starting with a natural source with chemical modification to a human hormone.