Our services

Control of microbial burden of non-sterile pharmaceutical products (EP 2.6.12/2.6.13, USP 61/62)
  • Method suitability test
  • Sample analysis


Bacterial endotoxins test (EP 2.6.14, USP 71)
  • Method suitability test
  • Sample analysis
Particulate matter analysis (EP 2.9.19, USP 788/789)
  • Method I, Light obscuration method
  • Method II, Microscopy method
Preservative efficacy testing (EP 5.1.3, USP 51)
  • Method suitability test
  • Sample analysis
In vitro genotoxicity test (ICH M7) - AMES test
  • Bacterial reverse mutation test (Ames test) OECD TR 471
  • Ames test Micro Plate Fluctuation assay

The Ames test is an in vitro assay for the detection of the genotoxic potential of various chemical substances including nitrosamines.

The bacterial reverse mutation test uses amino-acid requiring strains of Salmonella typhimurium and Escherichia coli to detect point mutations, which involve substitution, addition or deletion of one or a few DNA base pairs.  Following the OECD 471 Guideline for the Testing of Chemicals, four S. typhimurium strains, TA98, TA100, TA1535, and TA1537, and one E. coli strain, WP2 uvrA, will be used.

Biological assays

Microbiological assay of antibiotics - EP 2.7.2, USP 81

Heparin biological activity

  • Method development (USP 1032)
  • Method validation (USP 1033)
  • Sample analysis
Environmental moniroting sample analysis

Exposure, contact plates- Incubation and analysis

Filter validation studies (PDA TR 26, ISO 13408-2:2018)

Sterilizing filtration is the process of removing microorganisms from a fluid stream without adversely affecting product quality. To this end, most filter manufacturers provide results of tests performed according to applicable compendial methods to qualify their filters as suitable for pharmaceutical applications. However, this qualification documentation supports but does not replace, performance qualification as part of process validation conducted by the filter user. Qualimetrix facilitates this task, by undertaking the following tests according to PDA technical report No 26/2008, for which a short description is given:

  • Filterability test: The scope of the filterability test is to evaluate the potential clogging of the membrane by measuring the rate of the filtration (filtered weight against time), under constant pressure. This test also serves as a means of predicting manufacturing-scale performance by using flux and pressure conditions representative of the actual process.
  • Filter extractables (and potential leachables): It is a crucial part of filter validation studies to ensure that the filter does not adversely affect the process stream. To this end, filter extractable and possibly filter leachable species should be assessed. Extractables are chemical compounds that can be extracted from product contacting surfaces when exposed to an appropriate solvent under exaggerated conditions (i.e. time and temperature). Leachables are chemical compounds that migrate from a contact surface into the drug product or process fluid during storage or normal use conditions. The first step of the approach followed is to perform an extraction study with a suitable model solvent simulating worst-case conditions. Non-specific methods, such as non-volatile residue (NVR) and Fourier-transform infrared spectroscopy (FTIR) are employed to provide general quantitation and qualification of potential leachables. This represents the essential and simplified approach. nvr
  • Alternatively, and upon client’s request, an extensive extractable species profile assessment can also be implemented, by using various extraction media, to cover and extract the total pool of potential leachables, and by employing specific orthogonal techniques (LC/UV/MS, GC/MS, ICP/MS) to address their chemical diversity and provide information with respect to both their identity and concentration levels. The second step is to evaluate the levels of extractables following a risk-based methodology in order to determine the need for conducting a leachable species study. Both extractables and leachables testing for filters and other production-related materials (e.g., tubes) are an integral part of our services portfolio.
  • Compatibility: It is well known that numerous chemical interaction possibilities exist in a filter system. The effects of these interactions should be adequately characterized prior to filter selection and in most cases a simple chemical compatibility chart will not often provide enough information for predicting filter system compatibility, thereby requiring additional testing. Integrity testing is a non-destructive test that relates to microbial retention and is a determinant of compatibility. This test can be performed by means of either a diffusive / forward flow or bubble-point test. It is worth noting that both extractables and integrity testing constitute a combination of tests that serve to establish compatibility and detect subtle incompatibilities that a single test is usually not able to reveal.
  • Viability study: In order to determine the appropriate challenge test methodology, the test organism’s viability should be verified by direct inoculation into the carrier fluid (product or surrogate). To this end, the test filter membranes are exposed to the product solution, under worst case processing conditions in order to determine the effect of the product on the viability of Brevundimonas diminuta (ATCC 19146) for a given filtration time and define the most suitable method of performing a liquid bacterial challenge test for product and process specific filter validation.
  • Bacterial challenge: The bacterial challenge test validates filter membrane classification and demonstrates complete microbial removal from the product. The challenge organism is inoculated into the product (or surrogate) to deliver a minimum challenge level of 107 cfu/cm2 of filter surface area. The bacterial retention validation study should demonstrate that the filtration process of the product with the use of the specified filter, achieves the consistent removal of the high levels of the standard bacterium Brevundimonas diminuta (ATCC 19146) during the simulated processing conditions.

Optionally and upon request, an adsorption test can also be performed, in order to assess potential product binding to the filter membrane that could affect product composition and concentration.


ESPA Banner