Toxikon-Europe performs sterility tests under the most stringent test conditions in a sterility isolator. All materials and test items enter the isolator through a transfer hatch. Before entering the manipulation area the outer surfaces of all materials are decontaminated using Vaporised Hydrogen Peroxide (VHP). This prevents the manipulation area from being contaminated and assures an absolute sterile working environment. When performing sterility tests in a well validated isolator, the risk of a false positive sterility test is virtually down to zero. When the test is performed in a sterility isolator, the influence and the efficacy of the surface decontamination should be validated. This way, false negative results can be excluded.
In order to validate the possible penetration of VHP through the packaging material, the test items are inoculated with a small number of S. aureus. Subsequently the outer surface of the test items are decontaminated in the transfer hatch of the isolator and the viability of the micro-organism is determined.
Pyrogens are a group of substances capable of eliciting a fever response upon injection or infection. Endotoxin is a subset of pyrogens that is strictly of gram negative bacterial origin. Dozens of microbiological compounds have been found to either induce fever but many do so only weakly or only at very high doses. Most reactive (by far), most occurring and most resistant to extreme conditions of all possible pyrogens are gram-negative bacterial endotoxins. This is why the focus of pyrogens is mainly on endotoxins. LAL-activation is considered analogous to the response that is considered to be pyrogenic but is more specific for bacterial endotoxin and at much lower levels of detection. Endotoxins or Lipopolysaccharides (LPS) are a part of the outer cell wall of gram negative bacteria.
Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests: USP <61>, EP 2.6.12
These tests will allow quantitative enumeration of mesophilic bacteria and fungi that may grow under aerobic conditions. The tests are designed primarily to determine whether a substance or preparation complies with an established specification for microbiological quality. Validation: Suitability of the counting method in the presence of product.
For each type of product where bioburden is to be determined, the applied microbial recovery method should be determined during a validation study prior to the routine application of the desired method.
An artificial bioburden of less than 100 CFU of one of the following organisms will be applied onto the test item: Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Candida albicans or Aspergillus niger. Subsequently the bioburden of the test items will be determined using the selected method. A count of any test organism not differing by a factor greater than 2 from the value of the control in absence of the product must be obtained.
If growth inhibition is noticed, the use of a suitable neutralizer should be validated.
Total Aerobic Count
2 x 10 mL of the product will be membrane filtered and the membranes transferred once to Trypticase Soy Agar (TSA) plates and once to Potato Dextrose Agar (PDA) plates. TSA plates will be incubated for 3-5 days at 30-35°C. PDA plates will be incubated for 5-7 days at 20-25°C. The results are expressed as CFU/g. Acceptance criterions can be found in specific monographs of the pharmacopeia.
Toxikon Europe provides Lot release testing services for medical devices:
- Sterility tests: (ISO 11737-2) - Bioburden: (ISO 11737-1) - Bacterial Endotoxins (LAL): USP 85, USP <161>, EP 2.6.14
Also Specialty Studies such as:
- Sterilisation Validation Programs: ISO 11137 - Anti-microbial Efficacy / Time Kill Kinetic Assays - Cleaning Validation and Life Cycle Validation of Reusable Medical Devices - Microbial Integrity Studies
We currently provide programs for assessing product and technology compatibility/feasibility, method development and validation together with regulatory support. Once regulatory approval is obtained, technology and method can be transferred to the manufacturing site if decided to insource, or testing can be provided by Toxikon. We support you in overcoming hurdles as large equipment investments, having a multi-disciplinary team available (technical, validation, quality and regulatory experts) and time constraints.
Current RAPID micro services include: - Sterility testing (< 4 hours) - Microbial Limit testing of non-sterile products (2 days) - Microbial quality control of pharmaceutical water and cell growth medium (< 4 hours) - Environmental Monitoring (4 hours) - Endotoxin testing (2 hours)
Toxikon Europe provides comprehensive analytical services for all stages of product development, from concept to final product. Toxikon is a contract research organisation, FDA registered and ISO 17025 GLP GMP accredited, providing a complete suite of services for the qualification and registration of medical devices. Other capabilities are lot release testing, material characterization and extractable/leachable studies. Laboratories in Europe and USA.
With nearly 40 years of experience in medical device testing (including biocompatilbity, analytical chemistry, toxicology, microbiology, and risk assessment), we strive for operational excellence while continuing to implement the latest techniques and methods in our laboratories. This is only possible due to the intense scientific and regulatory collaborations we have forged with individuals both internal and external to Toxikon; including key opinion leaders (KOLs), subject matter experts (SMEs), and authorities on pertinent topics and guidelines.
Our partnerships have provided Toxikon with the broad vision necessary to navigate the complex and ever-evolving regulatory landscape, not only for today, but also for the future. This allows us to focus on the customer. We take great consideration to propose only the necessary activities needed to successfully support the preclinical development of their product, ultimately mitigating risk accordingly and maximizing project efficiency.