Microbiological quality control of non-sterile products

When determining whether a substance or preparation complies with established microbiological quality, it is important to use the correct media. The three internationally most important Pharmacopoeias (EP/JP/USP) published harmonized versions of their chapters on microbial examination of non-sterile products in 2009. In addition, the 2016 edition of the Chinese Pharmacopoeia is, for the most part, harmonized in terms of media composition and performance criteria, although growth promotion testing is required to be performed with strains from the Chinese strain collection. These methods address the total aerobic count (TAMC and TYMC) as well as the test for specified microorganisms.

Our culture media portfolio for microbial examination of non-sterile products is fully compliant with the harmonized Pharmacopoeia. As compendial methods change, be assured that we monitor this thoroughly, and any changes to composition or performance testing will be implemented quickly so that you won’t need to worry about the regulatory compliance of our media. We provide a choice of products for all culture media and substances required for

  • Sample Preparation
  • Microbial Enumeration Tests
  • Tests for Specified Microorganisms
Compendial Methods

European Directorate for the Quality of Medicines and Healthcare. (2017): The European Pharmacopoeia. 9th Ed. Chapter 2.6.12 Microbiological examination of non-sterile products: Microbial enumeration tests and Chapter 2.6.13 Microbiological examination of non-sterile products: Test for specified products. Strasbourg, France. Japanese Ministry of Health, Labour and Welfare. (2016): The Japanese Pharmacopoeia. 17th Ed. Chapter 4.05 Microbial Limit Test I. Microbiological examination of non-sterile products: Total viable aerobic count and II. Microbiological examination of non-sterile products: Test for specified products. Japanese Ministry of Health, Labour and Welfare. Tokyo, Japan. United States Pharmacopeial Convention. (2014): The United States Pharmacopeia 38/National Formulation 33, Supp. 2. Chapter <61> Microbiological examination of non-sterile products: Microbial enumeration tests and Chapter <62> Microbiological examination of non-sterile products: Test for specified products. Rockville, Md., USA.

Preparation of the Sample

Depending on the properties of the products to be tested, there are choices of dilution media and additives.

Table 1.Sample preparation

Many products bear antimicrobial properties which may be countered by adding neutralizing agents. The following agents are suggested by Pharmacopoeia

Table 2.Neutralizing agents for interfering substances

Microbial Enumeration Tests

Microbial Enumeration Tests are quantitative methods to determine a product’s level of contamination with mesophilic bacteria and fungi that grow under aerobic conditions.

The tests are comprised of total aerobic microbial count (TAMC) and total yeast and mold count (TYMC).

Depending on the product to be tested, the most appropriate enumeration method can be chosen from

Membrane Filtration, Plate-Count methods, or the Most- Probable-Number (MPN) method.

Before a method is chosen, the suitability needs to be proven in the presence of the product. This involves the preparation of suitable test strains, growth promotion tests of the culture media, as well as suitability tests for the counting method in the presence of the product.

Table 3.Sample preparation

Diagram: Microbial Enumeration Tests

Diagram: Microbial Enumeration Tests

Tests for Specified Microorganisms

Tests for Specified Microorganisms

Depending on the microbiological quality specification of each non-sterile pharmaceutical product, the manufacturer is required to determine the absence or limited occurrence of the following seven organisms:

  1. Bile-Tolerant Gram-Negative Bacteria
  2. Escherichia coli
  3. Salmonella
  4. Pseudomonas aeruginosa
  5. Staphylococcus aureus
  6. Clostridia
  7. Candida albicans

These organisms serve as general indicator organisms, but depending on the nature of the product, its designated use, the recipient group and method of application, other pathogenic microorganisms may be relevant. The following overview of required media is limited to explicit Pharmacopoeia requirements.

Test for Specified Microorganisms

Test for Specified Microorganisms
Materials
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