Ensure that your system, process or procedure is demonstrably ready-for-use!
A validation means the documented proof that a process, test procedure or system meets the previously specified requirements (acceptance criteria) reproducibly in practical use.
A validation is always required if the result of a process cannot be verified by a test.
With regard to patient safety in the field of medical technology and pharmaceuticals, validations are indispensable.
Our laboratory is accredited for the following validations and the necessary tests. The following list is intended to show some of our validation activities. We can carry out other validations at any time on request.
- Packaging validation as per ISO 11607 (more)
- Performance check or transport validation according to ISO 11607 (more)
- Cleaning validation (more)
- Reprocessing validations according to ISO 17664 (more)
- Validation of the endotoxin or pyrogen determination according to Ph. Eur. 2.6.30, 2.6.14 and 5.1.10, ANSI AAMI ST 72 and USP chapters 85 and 161 (more)
- Validation of microbiological test methods (microbial count determination and sterility testing) according to ISO 11737 or Ph. Eur. 2.6.1 and 2.6.12 (more)
- Validation of gamma sterilisation (more)
- Validation of further sterilisation methods (e.g. steam sterilisation, non-standardised sterilisation methods according to ISO 17665, ISO 14937, ISO 14160) (more)
In addition to these common validation activities, we have already repeatedly proven our competence in the
- development and validation of complex, product-specific test methods.
- validation of aseptic production processes.
With our comprehensive expertise, we are sure to find the right validation strategy for your question and test.
Packaging validation as per ISO 11607
Due to our many years of experience in the field of packaging testing of medical devices, we offer comprehensive skills and advice in the field of packaging validation.
We advise our customers in the selection of testing methods. Together with our customers, we design the test planning and evaluate the test results in comprehensive reports. Our documentation and working methods are based on ISO 11607.
We consult on and check all steps necessary for a complete packaging validation, such as
- validation of the sealing process through operational qualification and performance qualification including statistical evaluation (e.g. by determining the Cpk value)
- Inspection of the compatibility of the packaging with the sterilisation process (incl. statistical evaluation and creation of X- and R-bar charts)
- Inspection of the long-term stability of the packaging using data from accelerated or real-time ageing (incl. statistical evaluation and creation of X- and R-bar charts)
Performance check / transport validation
In order to ensure product safety and sterility even during transport, the ISO 11607 standard requires performance testing in the form of transport validation.
We conduct these for our customers through the involvement of qualified cooperation partners. During a transport validation, e.g. according to ASTM D7386 or ISTA 2A, the finally packed products are exposed to various stresses which serve to simulate transport, such as temperature and humidity changes, vibration, drop test, negative pressure, etc. Once the packaging has gone through the defined test sequences, a visual examination of the individual components of the packaging system can be carried out. In addition, our test methods for checking packaging integrity are also applied here.
Sterile medical devices are usually manufactured and packaged under cleanroom conditions. This limits the contamination of the products with microorganisms or endotoxins released by them.
While sterilisation-resistant endotoxins pose an immediate risk to patients, it is necessary to limit the bacterial count in order not to endanger the success of the subsequent sterilisation.
In addition to production under cleanroom conditions, disinfectant cleaning of the medical devices prior to final packaging is crucial. By integrating a cleaning step, the cleanroom production conditions can often be limited to the subsequent packaging processes.
Validation is necessary to demonstrate an effective cleaning process. In the course of simulated cleaning with artificially contaminated products, our laboratory can test the effectiveness of cleaning for the removal/inactivation of microorganisms or endotoxins.
In addition, the cleaning process can also be examined for its suitability for removing specific production residues. This may be done through chemical analysis and/or cytotoxicity testing. The goal is to prove whether the presence of toxic residues can be expected after the production process and final cleaning.
Our technical experts will advise you comprehensively on the definition of the cleaning processes for your product, draw up the validation plan together with the selection of the appropriate test soiling and the appropriate detection systems, carry out the cleaning simulation (on site), determine the residual soiling, evaluate the cleaning success and draw up a conclusive validation report.
Reprocessing validation of medical devices according to ISO 17664
The reprocessing of medical devices can be very extensive, depending on the type of medical device. We consult and plan with our customers and work out the requirements for the validation of reprocessing.
We follow the guidelines of the DGKH, DGSV and AKI for the validation and routine monitoring of mechanical and manual cleaning and thermal disinfection processes for medical devices. In addition, we also have the know-how and methods to meet the requirements of the FDA Recommendations "Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling" of March 2015, such as the use of two quantitative methods to determine residual soilage, end-of-life checks through accumulation studies, validation of extraction conditions, etc.
Take advantage of our expertise right from the drafting of the instructions for use as well as the preparation of the validation plan. Benefit from our know-how in the selection of suitable test soiling and the matching detection systems. We offer advice on defining your device’s areas that are most difficult to clean as well as on the definition of product families and the selection of suitable test samples. We carry out the cleaning simulation on the contaminated samples and determine the residual contamination. We prepare the samples for sterilisation testing by applying suitable test microorganisms, packaging the contaminated test samples and arrange for the necessary sterilisation runs to be carried out. Then we evaluate the samples and the controls by means of sterility testing. We subsequently prepare a comprehensive validation report.
We can offer our customers the following services as part of a reprocessing validation:
- Validation of partial steps: cleaning, disinfection and sterilisation using protein-blood mixtures or microorganisms
- validation of manual and machine cleaning
- determination of the number of permissible reprocessing cycles (service life)
- accumulation studies (multiple reprocessing)
- quantitative protein determination by BCA assay
- quantitative haemoglobin determination
- qualitative luminol test or amido black detection test
- validation of extraction conditions to verify residual contamination
Validation of pyrogen and/or endotoxin determination
For the validation of the pyrogen and/or endotoxin determination, if possible three batches of a product are tested according to chapter 5.1.10 of the European Pharmacopoeia. As per ANSI AAMI ST72 two to ten products per batch are tested and three to ten products are to be inspected as a merge sample according to USP chapter 161.
The interference factor analysis is important for the detection of endotoxins and pyrogens. The goal here is to demonstrate that the detection system is not disturbed in the presence of the product. For this purpose, a known amount of endotoxin is added to the preparation and then checked to see whether this amount can be detected. The recovery should be between 50 and 200 % to be able to rule out interfering factors.
For further information on testing for bacterial endotoxins and pyrogens according to Ph. Eur. 2.6.14 or 5.1.10, according to ANSI AAMI ST 72 and USP Chapters 85 and 161 and monocyte activation according to Ph. Eur. 2.6.30 see Services/Testing laboratory Microbiology.
Validation of microbiological test methods (microbial count determination and sterility testing) according to ISO 11737 or Ph. Eur. 2.6.1 and 2.6.12
According to the intention of the pharmacopoeia, the test methods described therein are already validated. However, these methods must still be validated to see whether they are generally suitable for testing the specific sample.
In the microbiological test methods, this is done by a so-called growth suitability test, often also referred to as bacteriostatic/fungistatic test. It is tested whether certain reference strains show equally good growth reactions in the presence and absence of the product to be tested.
The ISO standard goes far beyond the requirements of the pharmacopoeia, as it does not only require a test of the growth conditions on the basis of reference microorganisms. In addition to the bacteriostatic/fungistatic test, a comparative microbial count is carried out using different nutrient media and incubation conditions to check under which conditions most microorganisms and their species are detected. Since medical devices (in contrast to pharmaceuticals) usually have to be extracted in order to remove the adhering microorganisms and transfer them into the test solution, it is usually necessary to check the microorganism’s removal procedure in order to determine the recovery rate and derive a corrective factor from this.
The test is particularly complex if the samples contain antibiotics, for example, or if they are sponge-like products. These types of products can worsen the process of removing microorganisms immensely. Products containing antibiotics can possibly cause toxic effects on the microorganisms during the detachment process.
Validation of gamma sterilisation
The validation of the gamma sterilisation is subdivided into:
In addition to the application-technical validation and dose distribution measurement, gamma sterilisation also requires the validation of microbiological sterilisation.
This is the minimum irradiation dose required to bring the product into the sterile state. The initial microbiological state - number and type of microorganisms - is determined for this purpose. On the basis of the initial state, a certain dose, the verification dose, is determined. The products are irradiated with this verification dose and then tested for sterility. If the verification dose has been successfully verified by the sterility test, the sterilisation dose shall be confirmed. In doing so, it can be guaranteed that the validated sterilisation dose reaches a Sterility Assurance Level (SAL) of 10-6.
The sterilisation validations in our company are based on the following standards: ISO 11137-1, ISO 11137-2, ISO 11737-1, ISO 11737-2 and EN 556.
As far as possible, we recommend the so-called VDmax25 method and method I. The VDmax25 method is suitable for the validation of sterilisation with a minimum dose of 25 kGy (the usual method) and a bioburden of not more than 1000 CFU/product unit.
Method I, which is also widely used, is suitable for determining a minimum irradiation dose necessary for successful sterilisation. With this method, lower sterilisation doses can be achieved with demonstrably low microbial count, which are gentle on the product.
Revalidation / dose of gamma sterilisation audits
In addition, we offer our customers sterilisation dose testing to prove consistent efficacy by means of a typically quarterly revalidation (dose audit). Compared to microbiological validation, we only need a fraction of the test sample here. The dose audit consists of a microbial count determination (bioburden determination) and a check of the verification dose determined in the validation.
Special requests regarding gamma sterilisation
At the customer's request, individual batch validations and VDmaxSD methods in accordance with ISO/TS 13004 can be carried out in our company.
Building on our numerous years of expertise, we can advise you comprehensively on the selection of the most suitable validation method for your product at any time.
The determination of the dose distribution ensures that the determined dose is adhered to in all areas with specified packaging and packing arrangement. For this dose distribution measurement / dose mapping, a large number of dosimeters are attached to the sterilisation unit as shown in the figure. These dosimeters can be used to determine the product-specific minimum and maximum doses as well as the permissible dose range at the routine measuring point.
The manufacturer must check whether the sterilised product fulfils its property profile beyond the expiry date. The packaging material must be included in this. The materials selected for the product are considered to be decisive for the application of radiation sterilisation. We will be happy to advise you on this during product and packaging development. An initial overview in the form of publications about the procedure can be found on the homepage of the Gamma Irradiation Panel. If you have any questions regarding the compatibility of your material with gamma radiation, please contact our contact persons. We generally recommend our customers to conduct a trial sterilization to determine the maximum tolerated radiation dose.
Validation of further sterilisation processes
At our company, we have extensive experience with
- general sterilisation validation according to ISO 14937
- sterilisation with liquid/chemical sterilisers according to ISO 14160
- validation of steam sterilisation according to ISO 17665
- validation of dry heat sterilisation according to ISO 20857
We will also support you in the development or validation of further new or non-standard sterilisation processes. You can thus benefit from our extensive experience. For example, we can support you in analysing the microorganisms of the product-specific bioburden that are hardest to inactivate and determining their inactivation kinetics. Building on this, the validation of the sterilisation process can then be tackled.
Your contact persons
Should you have any questions about our services, please do not hesitate to contact us.