Advancing Sterility Testing in Pharmaceuticals
Sterility testing is a critical process in the pharmaceutical industry, essential for verifying the absence of viable microorganisms in sterile products before their release. This testing is crucial for ensuring the quality, safety, and compliance of sterile products, including parenterals, injectables, medical devices, and ophthalmic products. Advanced techniques and adherence to regulatory standards are vital for protecting patient well-being and maintaining product purity.
Microbial data deviations can lead to severe consequences, such as compromised patient safety. Therefore, strict adherence to sterility standards is necessary for regulatory compliance and to meet the requirements of major pharmacopeial chapters, including USP <71>, Ph. Eur. 2.6.1, and JP 4.06, harmonized in ICH Q4B Annex 8 guideline.
Using a closed filtration sterility test system with a peristaltic pump enhances test integrity by minimizing the risk of secondary contamination, ensuring reliable and accurate results, and improving contamination control. Such closed systems also improve laboratory safety by reducing the exposure of personnel to hazardous substances and providing precise control over fluid flow rates for consistent results.
In the late 1960s, Sartorius collaborated with scientific institutes and the German pharmaceutical industry to develop the reusable closed sterility test, a precursor to today's single-use systems. The Sterisart® family, a product of continuous innovation over decades, exemplifies a commitment to quality, safety, and regulatory compliance, setting new standards in sterility testing.
Consumables & Instruments
Featured Resources
Related Resources
Additional Resources
Frequently Asked Questions
Sterility testing is designed to verify the absence or presence of viable microorganisms in a sample of a product or substance. It is critical for products such as injectable drugs, vaccines, surgical implants, and other medical devices that come into direct contact with the human body. Sterility testing is a method used to assess a Critical Quality Attribute (CQA) of products that require aseptic conditions, determining the purity, efficacy or safety of sterile healthcare products.
- Direct Inoculation Method: A sample of the product is directly transferred or injected into a suitable culture medium. This method is adopted only if the product is non-filterable
- Membrane Filtration Method: This is the method of choice, prescribed by all pharmacopoeias. In this method, the product is filtered through a membrane filter with a defined pore size. The filter retains any microorganisms present in the sample.
Membrane filtration is suitable for testing larger volumes of liquid products and is less susceptible to interference from antibiotic substances, making it suitable for a broader range of products.
Sterility testing mandates the use of membrane filters featuring a nominal pore size of no more than 0.45 µm. The membrane material must be compatible with the product under examination. For instance, some products may contain antibiotics (bacteriostatic/fungistatic) substances that nonspecifically adhere to the membrane, potentially hindering microbial growth. It is essential that the membrane material remains chemically inert to avoid interference with the product or microbial growth. Additionally, certain products might contain substances capable of interacting with or damaging specific membrane materials. Evaluating the throughput or flow rate of the membrane is another crucial factor. These aspects are typically evaluated through growth promotion and method feasibility tests during the validation process.
Using an appropriate nominal pore size helps to avoid false-negative results. If the pore size is too large, smaller microorganisms may pass through the filter, leading to false negatives. A nominal pore size of 0.45 µm ensures that the membrane effectively captures a broad range of microorganisms, allowing for accurate detection of microbial contamination in the tested product.
The growth promotion test verifies that the culture medium used in the sterility testing process is suitable for supporting the growth of a wide range of microorganisms.
Method feasibility testing helps assess whether the selected sterility testing method is suitable for the specific product. Potential challenges and limitations, such as potential interference from the product matrix, can be identified, allowing for optimization of critical testing parameters such as the type of canister/membrane used, the type of rinsing fluid used, and whether a pre-dilution of a product sample is required.
Environmental isolates are tested in addition to the microorganisms specified in the major pharmacopeial chapters to allow for the identification of facility-specific risks. This enhances the comprehensiveness and robustness of quality control measures and helps identify any potential weaknesses or limitations in the test method. Some regulatory authorities may require the testing of environmental isolates as part of validation protocols.
Major pharmacopeial chapters such as USP <71>, Ph. Eur. 2.6.1, and JP 4.06 provide guidance on growth promotion tests, method feasibility tests, the minimum quantity and number of items per batch to be used for testing. Regulatory/industry guidance documents, such as the ICH guideline Q4B Annex 8, TGA guidelines for sterility testing of therapeutic goods, 21 CFR 610.12 – General Provisions, PIC/S PI 012-2, are also invaluable sources of information.
Method revalidation is typically performed when there is a change in the product formulation, an existing test method, or a change in the manufacturing process/ environmental condition that may impact product sterility. However, the Pharmaceutical Inspection Co-operation Scheme (PIC/S) 11.6.2.4 and the Therapeutic Goods Administration (TGA) guidelines on sterility testing (407) also recommend periodic revalidation (every 12 months) to ensure the ongoing reliability of the method.
