Microbial limit test

United States Pharmacopeia (1995) 23rd revision. Rockville, MD US Pharmacopeial Convention. (Note the section dealing with microbial limit tests.)... 

Microbiological aspects will need to be discussed, but the amount of information will depend on the type of product. For nonsterile products there will need to be a description of the microbiological attributes of the product and, if appropriate, a rationale for not performing microbial limit tests. For preserved products the selection of the antimicrobial preservatives will need to be discussed and the effectiveness of the selected system demonstrated. For sterile products there will need to be appropriate process validation data and information on the integrity of the container-closure system. 

The tests for microbial limits and recommendations for microbial quality criteria of raw materials, excipients, drug substances, and pharmaceutical products have been established in pharmacopoeial compendia for over 30 years. These tests are listed in the USP 24 Chapter (61) Microbial Limits Tests and in the Ph. Eur. 3rd ed.. Biological Tests 2.6.12 and 2.6.13, Microbial Contamination of Products Not Required to Comply with the Test for Sterility (total viable count, tests for specified microorganisms) and the JP XIII 30 Microbial Limit Test. 

The USP 24 General Notices state that alternative methods may be used to determine that products comply with the pharmacopoeial standards for the advantages in accuracy, sensitivity, precision, selectivity, adaptability to automation or computerized data reduction, or any other special circumstances. Such alternative or automated methods shall be validated However, when disputed, the compendial method is conclusive as it is the official or referee test. In addition, USP Chapter (61) Microbial Limit Tests states that automated methods may be substituted provided they are validated and give equivalent or better results, whereas USP Chapter (71) Sterility Tests states that alternative procedures may be employed to demonstrate that an article is sterile, provided the results obtained are at least of equivalent reliability. 

Tablets, powder- and liquid-filled capsules Microbial limit test, TAMC, TCYMC only Test development, scale-up and validation batches only 0, 6, 12, 24, 36 months...

Topical liquids, ointment, creams a. Microbial limit test, TAMC, TCYMC only b. USP AET for various use A < 0.75 test development, scale-up and validation batches only A > 0.75 all batches on stability for microbial limit first three batches for AET a. b. 0, 6, 12, 24, 36 months 0, middle of stability period and expiry... 

The following principles apply to microbial limit testing within a pre- and postmar-keted product stability program. 

The inclusion of the a routine microbial limit test in a marketed product stability protocol depends on the pharmaceutical dosage form. Typically, the test would be used only for nonsterile products, especially oral liquids, nasal sprays, and topical liquids, lotions, and creams that have sufficient water activity to support the growth of microorganisms. In contrast, tablets, powder- and liquid-filled capsules, topical ointments, vaginal and rectal suppositories, nonaqueous liquids and inhalation aerosols with a water activity too low to allow for the product to support the growth of microorganisms would not be routinely tested. 

To establish a microbial-limit testing history, all development, clinical, scale-up and process validation batches of new nonsterile dosage forms would be tested to verify that the pharmaceutical ingredients, manufacturing process, and packaging does not contribute to the bioburden of the product. After the testing history has been... 

USP 24 Testing Chapters (51) Antimicrobial Effectiveness Testing, (61) Microbial Limit Tests and (71) Sterility Tests, United States Pharmacopeial Convention, Inc., Rockville, MD, 2000. USP 24 Informational Chapters (1116) Microbiological Evaluation of Clean Rooms and other Controlled Environments, (1111) Microbiological Attributes of Pharmaceutical Articles, (1151) Pharmaceutical Dosage Forms, (1225) Validation of Compendial Methods, and (1231) Water for Pharmaceutical Purposes, United States Pharmacopeial Convention, Inc., Rockville, MD, 2000. 

A microbial limit test was performed on a routine basis and the 20 consecutive batches each showed conformance to specifications. 

Solubility characteristics in suitable solvents, including color and clarity evaluation pH value if API is soluble in water Microbial limits testing... 

BAM) for its microbial limit tests. Where the sample size is not defined in the limit, the results are based on the sampling procedures described in BAM. 

In general, bioburden counts in parenteral solutions are obtained by conducting the total aerobic counts and total yeast and mold counts as specified in the USP microbial limits test (61) or an equivalent test [72], In addition, membrane filtration of larger than specified volumes may also be used to detect any microbial contamination when sample results are expected to contain a negligible number of microbial flora or in the presence of potential confounding factors, such as antimicrobial... 

Usually, total aerobic bacteria, molds, and yeasts are counted by using a standard plate count in order to test the microbial limits. The microbial limit test may be customized by performing a screening for the occurrence of Staphylococcus aureus, Pseudomonas aeruginosa, Pseudomonas cepacia, Escherichia coli, and Salmonella sp. [56],... 

Opalchenova, G.A. Comparison of the microbial limit tests in the british, european, and united states pharmacopeias and recommendation for harmonization. Pharmacopeial Forum 1994, 20 (4), 7872-7877. 

The Microbial Limit Test is, like the Test for Sterility, only confirmatory. It is not generally mandatory to test each batch of every non-sterile product for compliance with microbial limits. The exception is in the United States where it is mandatory to test every batch of non-sterile product. At the time of writing (early 2001), the FDA has proposed a relaxation of this rule for future registrations. However, in the case of tablets there is no requirement to register microbial limits, and therefore testing is not mandatory. The logic behind this is that the water content of tablets is too low to allow proliferation of microbiological contaminants. 

Products not Required to Comply with the Test for Sterility (Total Viable Count, Tests for Specified Micro-Organisms) and JP Xin 30, Microbial Limit Test. 

---