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Frequently Asked Questions

What is involved in an Ethylene Oxide sterilisation validation

Reference Standards

  • ISO11135
  • ISO 10993-7
  • AAMI TIR documents

Installation Qualification

Installation qualification, or commissioning, verifies that the equipment has been installed and operates in accordance with its specification. The qualification is conducted in the absence of product.

2.0 Cycle Selection

The development and selection of a sterilization process for a particular medical device must establish that the procedure is both effective and compatible with the device. Cycle selection is typically based on the nature of product bioburden, packaging, manufacturing conditions, product materials and product volumes.

During an Ethylene Oxide (EO) sterilization process, products can be subjected to different stresses, including elevated temperatures and changes in humidity. Thus, product design should ensure that functionality and safety are not compromised by exposure to the anticipated range of sterilization conditions.

The product may also react with or retain EO residuals. A determination that the proposed process does not result in unacceptable levels of Ethylene oxide or by-products in the product must be made.

The effect of re-sterilization and maximum process parameters should also be investigated during this cycle selection study.


Protocol Preparation

Before initiating Performance Qualification, a protocol must be developed covering the key areas of Physical and Microbiological Performance Qualification.

Validation Load Selection

Single Product Load

When a single product is to be sterilized, the loading pattern should be defined for routine sterilization and the load used for validation should be assembled in an identical manner.

Physical Performance Qualification

The purpose of Physical Performance Qualification is to ensure that the sterilization load reaches acceptable levels of temperature and Relative Humidity (RH) by the end of the minimum preconditioning time, and further, that these levels are maintained within acceptable limits throughout exposure to EO. Analysis of the data gathered will identify any areas in the load that are difficult to heat or humidify. Profiling should be carried out for different configurations.

Microbiological Performance Qualification

The rate of microbiological inactivation for a given process is usually assessed using Biological Indicators of B. atrophaeus which contain a known population possessing resistance to EO sterilization. The appropriateness of these indicators should be established and documented.

During validation, BIs should be located within the parts of the products which present the worst-case scenario for gas and humidity penetration as identified in the Physical Performance Qualification. The remainder of the BIs should be distributed throughout the load at specified intervals.

EO residual Testing

Part of the sterilisation validation requirements under ISO 10993-7 is to evaluate product and packaging performance after exposure to the process. To ensure product safety, the levels of EO, Tolerable contact time and EO by-products should be determined after sterilization and de-gassing.

Review Reporting and Approval

A final report will be issued for customer approval. It will summarize the validation and detail the cycle specification. This report should be read in conjunction with the protocol and should be signed by the same individuals who approved the protocol.

What is the Half-cycle method ?

This method involves determination of the minimum time of exposure to EO, with all other process parameters except time remaining constant, at which there are no survivors. Two further experiments should be performed to confirm the minimum time. Both should show no growth from the BIs. The specified exposure time should be at least double this minimum time. A cycle of short duration cycle also called a sub-lethal cycle from which survivors can be recovered should also be run to demonstrate the adequacy of the recovery technique.

What is the Product Test Unit?

When more than one product is to be validated at the same time, the selection of test units must be justified and documented. Assess the complexity of each product with regard to gas pathway dimensions, material permeability, gas and humidity penetration, packaging materials, accessories, instructions for use booklets. The most difficult to sterilise location within the product must be identified and used in the validation. When the product is inoculated it is called an internal inoculated unit or iPCD

From the above, select the most challenging product from each family and compare these against an external Process Challenge Device (PCD) in a sub-lethal cycle. This will determine the ranking of the products and identify a suitable PCD for routine processing. 

What is Product Bioburden ?

This is the level of microbial organisms that could be present on the product prior to sterilisation. It is important to know the levels and types of microorganisms on the product. The microbiological contamination of product prior to sterilization should be minimized and controlled. For that reason, it is essential that this population is determined during validation and routinely monitored thereafter.

The applicable standard is ISO 11737

When should Revalidation be considered ?

Revalidation should be performed in cases where new products or changes in existing product, packaging or loading pattern which cannot be shown to be equivalent to those previously validated, are introduced.

Revalidation may include all or some aspects of the original validation. ISO 11135 standard recommends that the validation be reviewed at defined intervals against specified acceptance criteria and in accordance with documented procedures. A decision on whether revalidation is required must be documented and approved. 

Is it possible to validate a mixed load ?

When a range of products from a single manufacturer are to be sterilized together, the load

used for validation should reflect the most difficult combination of products. Validation for the mixed load should document the rationale for its selection (based on complexity and configuration), and the composition should be recorded in the protocol.

Factors, which may be considered in such a load, are those likely to affect penetration of heat, humidity and gas. For example: density (kg/m3),carton size, pallet configuration, packaging, as well as factors such as the compatibility of the products and minimum and maximum routine volumes of any one product/pallet in the load.

Gamma Irradiation are used in Gamma Sterilisation ?

  • ISO 11137
  • ISO 11737
  • AAMI TIR documents

What is Gamma Irradiation ?

Gamma radiation effectively kills microorganisms throughout the product and its packaging with little temperature effect through destabilisation of the DNA material.

Characterized by deep penetration and low dose rates of gamma radiation, permeable packaging materials are not required. Since there is no requirement for pressure or vacuum, package seals are not stressed. With gamma radiation, time is the only variable requiring control, so the possibility of deviation is minimal. As soon as the delivered dose of radiation is verified, products may be released for shipment. There are no residuals and no radioactivity concerns with Gamma sterilisation. 

What is E-Beam Irradiation ?

Electron beam processing has the ability to break the chains of DNA in living organisms, such as bacteria, resulting in microbial death and rendering the space they inhabit sterile.

Characterized by its low penetration and high dosage rates, electron beam radiation is a form of ionizing energy that performs best when used on low-density, uniformly packaged products

Electron beam processing involves irradiation (treatment) of products using a high-energy electron beam accelerator. Electron beam accelerators utilize an on-off technology, with a common design being similar to that of a cathode ray television. The electrons have a negative charge, they are repelled by the cathode and attracted to the anode. They travel in straight lines through the empty tube. The voltage applied between the electrodes accelerates these low mass particles to high velocities

Electron beam processing is used in industry primarily for three product modifications:

  • crosslinking of polymer-based products to improve mechanical, thermal, chemical and other properties,

  • material degradation often used in the recycling of materials, and

  • sterilization of medical and pharmaceutical goods

What is the difference in penetration rates between Gamma and E-Beam ?

The different forms of radiation penetrate items to quite different degrees. Electrons are much less penetrating than X-Rays and gamma rays. Most electrons collide with the product irradiated within a few atomic layers of the surface but each collision creates secondary electrons under the surface. These continue to create more electrons in a shower effect. Radiation is scattered forward and the peak dose actually lies a short distance below the surface. Thereafter it diminishes quite quickly. Electrons from electron accelerators have a usable penetration of about 3 mm in water for each million volts of accelerating potential. A 10 million volt (MeV) beam will therefore penetrate about 3 cm. In lower density materials, the penetration will be correspondingly higher.

What is dose mapping used for?

  • It provides information on products that can be processed together

  • Used to determine if a product can be added to an existing product category

  • Can be used to determine the impact of configuration changes in the variation of the dose

  • Dose mapping should be conducted to establish the effect of process interruption and results compared to normal processing

  • Dose mapping should be carried out if the density of the product changes, or if processing 2 products of different densities to determine effect on the dose and the dose distribution compared data with 2 products irradiated separately

  • May also dose mapping on partial containers to look at dose distribution, would also need to include adjacent load containers

What Considerations to be addressed during irradiation validation?

  • Product Material types
  • Bioburden levels
  • Product load density
  • Orientation of product in load
  • Density & Configuration of load
  • Max Acceptable dose

Description of the criteria to be established during irradiation validation ?

  • Preparation of a protocol
  • Description of the irradiation unit
  • Establishment of a maximum acceptable dose
  • Establishment of a sterilisation dose
  • Dose Mapping Exercises
  • Location of dosimeters
  • Review and approval of report