The provision of customized single-use consumables entails project-specific validation in practically every customer project as the configuration of any system is unique to some extent. Most of the relevant regulations and standards for validating single-use consumables originated from the medical device market or the market for finished pharmaceuticals with high volume production and lower part cost compared with average single-use consumables.

 

Achieving the right balance between product safety, regulatory requirements and commercial aspects for customized single-use consumables requires in-depth knowledge of all applicable regulations and standards as well as of the technical aspects and risks associated with any product, from the raw materials through to the production technology used. The scope of our validation capabilities encompasses:

 

  •          Particle testing
  •          Bioburden
  •          Endotoxins
  •          Leakage (pressure decay testing)
  •          Sterility
  •          Shelf-life
  •          Packaging
  •          Transportation / shipping

Applicable Regulations and Standards

  •          ISO 13485: Quality Management Systems for Medical Devices
  •          ISO 14644: Clean-Room Environmental Controls
  •          ISO 11137: Sterilization of Medical Devices
  •          ISO 11737: Bioburden
  •          E.P. 2.6.14 and USP <85>: Bacterial Endotoxins Test
  •          E.P. 2.9.19 and USP <788>: Particulate
  •          ASTM F 1980:2007: Standard Guide for Accelerated Aging of Sterile Barrier Systems for Medical Devices
  •          Materials of Construction (free of animal-derived ingredients or meeting EMEA410.01 rev.03)
  •          USP <661> Extractables / BPOQ Protocol
  •          ISO 10993 Biocompatibility
  •          USP <87> / USP <88> Cytotoxicity/Bioreactivity
  •          Transportation Validation (ISTA-2A or ASTM D7386-12)

Endotoxin Testing USP85

Typical single-use consumables are frequently used for fluid management in both upstream and downstream processes. Consequently, they have direct product contact and can potentially add undesired materials to the process. Bacterial endotoxins are examples of such undesired materials.

 

Bacterial endotoxins are gram-negative bacterial products which can be toxic and may cause symptoms such as fever. These materials cannot be completely removed by sterilization as the sterilization process will not inactivate the toxins even when cleaning and sterilization is effective in killing the bacteria. Consequently, bacterial endotoxin testing is an essential component of batch release testing. Details on test limits and methods are available on request.

Sterility ISO 11137

The sterilization process of any product must be validated to verify that it effectively and reliably kills any organisms that may be present on the presterilized product. If requested, our single-use consumables are sterilized to achieve a sterility assurance level (SAL) of 10-6, which corresponds to the probability of one in a million items being nonsterile. Validation is performed according to the ISO 11137-2 VDmax 25 method. Based on the annual production volume of every item, the sterilization dose is audited during routine production runs.

Leakage Testing

Parker Prädifa performs leakage testing using pressure decay (destructive and nondestructive) and submergence tests. Pressure decay testing is done with a dedicated device inside a clean room class 7. The device has a sensitivity of 1 Pa monitoring air loss inside single-use assemblies after they have been pressurized and the pressure has been stabilized. The acceptance limits for the pressure decay test are product specific and heavily depend on the component materials and size as various tubing materials for instance behave differently during a pressure decay test. The test result requires in-depth understanding of material performance characteristics. The submergence air bubble test is performed to verify if the acceptance limits used for every product during pressure decay testing are suitable. Parker pressure decay test results can be used to establish a correlation to integrity testing done after manipulation at the customer’s site.

Shelf Life

All sterile products requireshelf life testing of the product’s packaging as well as itsfunctionality in order to verifythe impact of aging on thematerials. In order to avoiddelays entailed by real-timeaging studies of the product(s),accelerated aging tests accordingto ASTM F 1980:2007 areperformed. In accelerated agingtests, it is important not to selectexcessively high temperaturesettings even though this reducestesting time and cost. Plasticcomponents in particular maychange in terms of mechanicalproperties and surfacecharacteristics if temperaturesfor accelerated aging are settoo high. Typical shelf life is 24months but may be extendedbased on the customer’s project-specificrequirements.

Contact

Parker Hannifin GmbH
Engineered Materials Group Europe
Arnold-Jäger-Strasse 1
74321 Bietigheim-Bissingen
Germany

Phone  +49 7142-351-0
Fax +49 7142-351-293