Sterilization 101

Considering and determining the mode of sterilization early in the development cycle of a new product is critical to its success.

As an example, the ability to sterilize a medical device product depends on a number of complex factors including design of the device, material selection, product packaging and final packaging.
There are four key modalities used to sterilize medical device products in their final packaging: Gamma, Ethylene Oxide, Electron Beam / X-Ray, and Steam. Below are brief descriptions and considerations for the use of each.
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Gamma Irradiation

For organizations whose goal is production of sterile product in its final packaging, of high- and/or low-density, in large and/or small volumes, gamma is a flexible, simple, efficient and effective sterilization modality.

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How it works:
High-energy photons (gamma rays) emitted from an isotope source (Cobalt-60) disrupt living cells by damaging the DNA and other cellular structures. These photon-induced changes at the molecular level cause death of organisms or render organisms incapable of reproduction.
When thinking about sterilizing with gamma, consider the following:
  • The gamma sterilization process is predictable and repeatable.
  • Though a radioactive metal is used in gamma processing, the process does not make the product radioactive nor leave a residue on the product.
  • Product can be shipped to the final user as soon as it exits the gamma irradiation facility.
  • Material selection is an important consideration when choosing gamma. Some polymers can become brittle and yellow, so organizations should work with their partner in advance to minimize the risk of this occurrence.
  • Gamma processing can be either an in-house or an outsourced process. The decision to build an in-house sterilization capability or outsource depends on a number of factors including the volume of product required, requirements of turn-around and value of the product. In some cases, you would need to work with a contract gamma processor or with Nordion to decide which is best for your business.

Pertinent industry standards:

  • ANSI/AAMI/ISO 11137-1 Sterilization of healthcare products – Radiation – Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices.
  • ANSI/AAMI/ISO 11137-2 Sterilization of health care products – Radiation – Part 2: Establishing the sterilization dose.

Ethylene Oxide (EO) Gas

For organizations whose product is particularly radiation sensitive, EO has been found to be an effective sterilization modality.

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How it works:
  • EO is an alkylating agent that disrupts DNA of microorganisms and prevents them from growing and multiplying on the surface of products being sterilized. An EO cycle includes a series of steps starting with product temperature conditioning, gas exposure, degassing and release of product.
When thinking about sterilizing with EO, consider the following:
  • The design of your product and packaging must allow for gas movement and exposure to a range of pressures at an elevated temperature.
  • The EO sterilization cycle could last several days because of pre-conditioning time and because treated products often require an 8- to 24-hour quarantine to ensure the gas is completely dispersed.
  • EO has a complicated validation process; therefore, microbiological testing is commonly conducted following the process and before product is released to ensure sterilization was achieved.
  • According to the World Health Organization (WHO), EO is carcinogenic and highly explosive. Organizations that use EO must comply with strict usage guidelines to ensure safety of the EO operations and product sterilized with the gas.
Pertinent industry standards:
  • ANSI/AAMI/ISO 11135-1 Sterilization of health care products – Ethylene Oxide – Part 1: Requirements for development, validation, and routine control of a sterilization process for medical devices.

Electron Beam (E-Beam) and X-Ray Irradiation

For organizations whose goal is production of sterile product of low-density or product packaged in small, uniform packages, E-Beam has been found to be an effective sterilization modality. X-ray could be an effective sterilization modality for the production of sterile product in its final packaging, of high density, in large volumes.

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How it works:
  • E-Beam and X-ray are very similar in how they work. An electron beam produced using an electric-powered machine source called an accelerator disrupts living cells through damage to DNA and other cellular structures. The low penetration properties of the electron beam means that the width and density of products that can be irradiated are limited.
  • X-rays are produced using an electron beam directed onto an X-ray converter target. The high-energy X-rays disrupt living cells through damage to DNA and other cellular structures. Because the radiation is in the form of photons, the depth of penetration issues with electrons is avoided; however, the conversion rate to X-rays is inefficient and therefore costly due to high electricity consumption.
When thinking about sterilizing with E-Beam and X-ray, consider the following:
  • E-Beam is ideal for sterilization or irradiation of low density, uniform product. For this reason it is often used to irradiate high volumes of plastic, wire and cable.
  • E-Beam sterilization is limited by the penetration of electrons, which is proportional to the accelerator voltage. This makes validation of heterogeneous or high density products harder.
  • Significant heating of product may occur due to the high rate of energy output of E-Beam, which may damage some products.
  • Industrial irradiators that use X-rays are relatively new. The first commercial facility designed and dedicated to sterilization of medical devices was opened in 2010. Consequently, availability of this modality on a contract basis is limited, and operational reliability is unproven.
  • X-ray sterilization is costly compared to any other modality due to the inefficiency of the technology as it exists today.
Pertinent industry standards:
  • ANSI/AAMI/ISO 11137-1 Sterilization of healthcare products – Radiation – Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices.
  • ANSI/AAMI/ISO 11137-2 Sterilization of health care products – Radiation – Part 1: Establishing the sterilization dose.

Steam Sterilization

For organizations whose product is not heat sensitive, conventional steam sterilization has been found to be an effective sterilization modality.

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How it works:
  • Steam sterilization delivers uniform heat to a product either through direct contact with the steam at a given temperature and pressure or indirectly through product packaging. Steam sterilization units can be large or small scale and are often used for in-house sterilization requirements.
When thinking about sterilizing with steam, consider the following:
  • It is non-toxic to humans.
  • It can be affordable and accessible.
  • Heat and/or moisture can be hazardous to the integrity of the product.
Pertinent industry standards:
  • ANSI/AAMI/ISO 17665-1 Sterilization of Healthcare Products – Moist Heat – Part 1: Requirement for the development, validation, and routine control of a sterilization process for medical devices.
Additional guidance available:
  • PDA (Parenteral Drug Association) Technical Report No. 48 (2010) Moist Heat Sterilizer Systems: Design, Commissioning, Operation, Qualification and Maintenance.
  • PDA Technical Report No. 1 (2007) Validation of Moist Heat Sterilization Process Cycle Design, Development, Qualification and Ongoing Control.

The Bottom Line

There are many considerations when sterilization is the required outcome: product characteristics, packaging, density, volume and more. It is best to collaborate with sterilization experts to ensure your unique product goal is achieved.
Modality Chart
Please note: Each of the referenced standards on this page have associated guidance documents. Also, for the radiation standard, there are several ASTM documents which are referenced and are now on the FDA-approved list including the following:
  • 14–341, Standard Guide for Absorbed-Dose Mapping in Radiation Processing Facilities, ASTM E2303—11.
  • 14–342, Standard Practice for Dosimetry in Radiation Processing, ASTM E2628—09 1.
  • 14–343, Standard Guide for Performance Characterization of Dosimeters and Dosimetry Systems for Use in Radiation Processing ASTM E2701—09.
  • 14–345, Standard Guide for Selection and Calibration of Dosimetry Systems for Radiation Processing, ISO/ASTM 51261 First Edition 2002–03–15.
  • 14–346, Standard Practice for Use of a Polymethylmethacrylate Dosimetry System, ISO/ASTM 51276 Second Edition 2002–12–15.
  • 14–347, Standard Practice for Dosimetry in Gamma Irradiation Facilities for Radiation Processing, ISO/ASTM 51702 Second Edition 2004–08–15.
 FDA list of recognized standards (see Section O. Sterility, Page 9).
 
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Radiation Technologies in Daily Life
We go through our lives mostly unaware of the use of radiation technologies to make things safer, cleaner and more efficient. When we travel by car or plane, get treated at hospital or even walk over a bridge, we may be experiencing the benefits of such technologies. This short 8-minute film by International Atomic Energy Agency (IAEA) goes behind the scenes to see these technologies at work and shows how they help us in our everyday lives. (Video courtesy of IAEA.)