Sterilization

Sterilization with with Gamma has a long history of over 30 years. X-Ray sterilization is increasingly used, since high performance and high- penetration (7 MeV) machines are on the market. Both methods are considered equivalent for sterilization.

Advantages of the process are:

• High intrinsic process safety
• Fast throughput
• Easy, parametric release, immediate usability without further testing
• Treatment in whole boxes (e-beam) or even pallets (Gamma)
• Treatment through dense packaging materials
• Easy process documentation and validation
• Widely accepted and recommended method
• Cold process, even for heat- sensitive goods

Possible obstacles may be:

• Transport to/ from contractor necessary
• Materials have to be qualified for the process

Radiation sterilization is mostly performed with:

• Medical devices
• Packaging materials
• Labware
• Raw materials
• Some cosmetic and pharmaceutical goods

Standards

Radiation sterilization is a standardized process, especially for medical devices. Relevant standards specific for radiation sterilization are for example:

Responsibilities

The manufacturer keeps the ultimate responsibility for his product. Responsibilities are normally defined as follows:

Topic	HARD	Supplier
Definition of the dose range		*
Validation of the dose definition		*
Validation of the dose suitability		*
Microbiological validation		*
Treatment SOP	*
Irradiator commissioning	*
Definition of the loading pattern	*	*
Assurance of the loading pattern	*	*
Dosimetry	*
Release of the final product		*
Stability tests		*
Packaging		*
Responsibility for transports		*

Sterility assurance

For medical products labeled as sterile, normally the following requirements are applicable:

• A sterility assurance Level (SAL) of at least 10-6 must be achieved.
• Historically, a radiation dose of 25 kGy minimal has been proven to be safe and effective to sterilize medical goods. Traditionally, this dose has been applied and no further verifications were made. 
  
• However, with the introduction of new standards, such as ISO 11137, requirements became more stringent. 
  

Today, the following methods to prove the effectivity of the applied radiation dose are common:

• A minimal dose of 25 kGy is applied. The bioburden of the goods before sterilization is monitored and documented to be low and consistent.
  
  
• A formal dose setting procedure as described in ISO 11137 is performed and the necessary dose to achieve the required SAL is determined.
  
  
• A Validation with bioindicators can be performed upon request. For Medical devices this proceeding is normally not recommended, a dose setting should be performed as described in the relevant standards (ISO 11137). However according to USP and European Pharmacopeia for pharmaceutical goods and packaging materials Bioindicators are still common. The goods are artificially contaminated with Bacillus pumilus or spore strips are placed in the load. It is useful to remove the bioindicators after half the routinely applied dose to be able to extrapolate the safety for the routine process.

Goods other than medical devices can be treated with lower doses, as for them a sterility assurance level as for medical devices is not always required. Common doses for packaging materials, labware and similar are between 5 and 15 kGy minimal dose. This will give less stress to materials and can save cost.
However, for an individual material, it is always recommended to test samples at the expected minimal and maximal dose, to assure a conforming treated product.

logarithmic decay of microorganisms under radiation

Units:

Bq: unit of activity: 1 Bq = 1 decay/s
Curie (Ci) : old unit : 1 Ci = 3.7 *1010 Bq
Gy, kGy: unit of absorbed dose: 1 Gy = 1 J/kg, 1 kGy = 1 kJ/ kg
rad, Mrad old unit 1 rad = 0.01 Gy, 1 Mrad = 10 kGy