Information on sterility testing

Sterility testing for cell therapeutic drugs is a critical part of ensuring that these products are free from microbial contamination and safe for patient use. The testing process typically covers several key components:

1. Testing Methodology

  • Direct Inoculation Method: A small sample of the product is introduced into a culture medium. If the product is sterile, no microbial growth will occur. This is one of the most common methods for sterility testing which we perform at Lab Quade using a fully automated blood culture bootle (e.g. Bactec FX) system.

  • Membrane Filtration Method: A sample of the cell therapeutic product is filtered through a membrane that traps any microorganisms present. The membrane is then placed in a suitable growth medium to detect microbial growth.

2. Test Organisms

Sterility testing must ensure that the product is free from a wide range of potential pathogens. The organisms tested for typically include:

  • Bacteria: Common pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.

  • Fungi: Such as molds and yeasts (Candida albicans, Aspergillus niger).

  • Mycoplasma: Mycoplasma species, which are often associated with cell-based therapies and can be difficult to detect due to their small size.

3. Sterility Testing Conditions

  • Incubation: The inoculated samples are incubated for an appropriate duration (typically 7 to 14 days) under conditions conducive to the growth of different types of microorganisms (such as different temperatures for bacteria and fungi). Preliminary reports are available after 48hours.

4. Test Duration

The sterility test usually lasts for at least 14 days (sometimes longer or shorter depending on the product and regulatory guidelines), with samples being checked at regular intervals for any signs of microbial growth. As Lab Quade uses fully automated systems positive results can be forwarded to the client within minutes.
A preliminary report is available to the client with 48hours.

5. Type of Products Tested

  • Cell Therapeutic Drugs: This can include stem cell-based therapies, gene therapies, and other biologics. These products require sterility testing to ensure that any microbial contamination during the manufacturing process is detected.

  • Starting material

  • Cell Culture Media: Often tested alongside the therapeutic product itself, since contamination in the media could lead to contamination of the final product.

  • Final Formulation: The product as it is intended for patient use, whether it’s a liquid or cellular suspension.

6. Regulatory Guidelines

Sterility testing must follow specific regulatory guidelines such as those from:

  • U.S. FDA (e.g., 21 CFR Part 610)

  • European Pharmacopoeia (EP)

  • United States Pharmacopeia (USP, including USP <71> for sterility testing)

  • International Conference on Harmonisation (ICH): Provides recommendations for sterility testing in biotechnology-derived products.

These guidelines specify acceptable limits for microbial contamination and the testing protocols to be used.

7. Contamination Detection

If any microbial growth is detected during sterility testing, it indicates contamination, and the product fails the sterility test. The source of contamination needs to be identified. Lab Quade features high-end mass spectrometry identification equipement.
Along with genetic profiling the type of contamination can be identified within short time frames.

8. Reporting

Lab Quade provides preliminary reports after 48hours, as well as final reports after 7 or 14 daye. However these times can be adjusted to the clients/regulatory body needs. All reports are available in english and german language and send to the clinet by email and paper copy.