Microbiology

Your contract laboratory for microbiological analysis in Switzerland

The microbiological investigation of pharmaceutical substances for manufacturing and of the finished products is prescribed by the pharmacopoeias of the various markets (Ph. Eur., USP, JP). The investigation must be performed in a GMP certified laboratory.

Careful surveying and experience are the key factors in the evaluation of microbiological quality. Depending on the product and the phase of production, the number of germs and particles and the endotoxin count must be determined. In the microbiological stability test, the growth inhibition effects of preservatives are proven.

As a GMP accredited and FDA registered leading contract laboratory in Switzerland, we offer you holistic consultation in the areas of microbiology and hygiene monitoring. If you would like to know what tests need to be carried out, and how the results should be interpreted, we can provide support. Do you have any question on the scope of necessity of a method validation?

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Your contact person
Sales pharmaceuticals

René Wicki

GRADUATE CHEMIST HTL

Tel. +41 58 434 42 00

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Harmonised regulations EP, USP, JP

Since 2009, there have been mandatory provisions for harmonised methods for all products. As a result, data for market approval can also be used in the areas of validity of the harmonised pharmacopoeias.

A microbiology laboratory in the pharmaceutical analysis department

Product-specific validation

To comply with GMP, all methods must be validated in a product-specific manner. Three independent run-throughs must be completed on a minimum of one batch. Here, the defined acceptance criteria will be tested. These criteria are given in the pharmacopoeias (Ph. Eur., USP, JP etc.) or are determined according to the specifications of the manufacturer.

If validation is planned, a method will be developed in pre-testing. Influencing factors such as solubility, recovery, reproducibility and matrix effects will be tested in the measurement range. The central question in method development is: Is the measurement method suitable?

Products with a reinforcing or inhibitory effect

If products increase or inhibit the growth of germs, then these factors must be neutralised by suitable adaptation of the methods. To do this, complexing agents, detergents and/or filtration are used.

Microbiological testing: Membrane filtration

Endotoxins: Measurement with the LAL test

Endotoxins from gram-negative bacteria are the most common cause of toxic reactions which can be brought about by the contamination of pharmaceutical products. Generally, product-specific validation is also necessary for the measurement of endotoxins. Here however, testing of three batches is mandatory to fulfil GMP compliance.

During method development, the decision to apply either a chromogenic or a turbidimetric kinetic test must be taken. Both tests allow quantitative determination of the endotoxin content.

Microbiological stability tests

If preservatives are used in a product to prevent the reproduction of micro-organisms, then testing for a sufficient level of preservation is mandatory. The requirements are dependent upon the intended purpose of the product. For the microbiological stability tests, the product will be inoculated with germs and germ reduction will be investigated at regular intervals over a specified period of time.

Carrying out a microbiological stability test

Germ determination - the basics

For determination of the total aerobic microbial count (TAMC) and total yeast mould count (TYMC), the number of colony building units on a solid culture medium (Agar) will be determined.

Should proof of specified micro-organisms be carried out, then selective culture media will be used. Evaluation is possible after 5 to 7 days. The results that are counted are then compared with the limit values.

The Interpretation of Limit Values

Limit values are given in the pharmacopoeias according to the product category or can also additionally conform to the requirements of the manufacturer. The specification regulations given in tables in the pharmacopoeias take into consideration the fact that microbiological methods come with a certain amount of uncertainty per se. Hence, a factor of 2 is allowed in the interpretation of the results, e.g. for a specification of ≤102 CFU/g, a maximum acceptable value of 200 CFU/g is admissible.

Investigating with an optical microscope

How do we guarantee the quality of the results?

For correct determination of the germ count, high requirements apply for the quality assurance of the culture media. Both self-produced and commercially available culture media must be tested for their suitability. Freedom from germs and growth promotion must be proven in suitable tests.