What does “sterile” mean according to the US Food and Drug Administration (FDA)?
According to the most stringent definition, a product or object is considered sterile if all living microorganisms—including bacteria, yeasts, viruses, and molds—are completely absent. Sterile is defined for regulatory reasons using acceptance criteria that are derived from the estimated chance of contamination. For the majority of items, the likelihood of one contaminated product out of a million made products is an acceptable amount of contamination risk. However, depending on the medical equipment or product’s intended purpose, sterility requirements may be more strict or less strict.
Why are sterilization validations necessary, and what are they?
The process that a product or device goes through to become sterile must be validated to demonstrate that sterility acceptance requirements are regularly met, as the sterility of a medical device or product is dependent on acceptance criteria. Only a verified sterilization procedure in accordance with current good manufacturing standards (cGMP) can guarantee sterility. Relying solely on routine sterility testing of finished goods is insufficient to prove sterility. Therefore, experiments that gather information about a sterilization procedure and statistically demonstrate that the procedure can reliably sterilize medical devices or items under “worst-case scenario” circumstances are known as sterilization validations.
Describe radiation sterilization, also known as radiation sterilization.
A non-thermal sterilization technique called “sterilization by radiation” uses gamma radiation, beta particles (an electron beam), x-rays, or ultraviolet light to kill microorganisms in a product. The only other sterilizing technique that doesn’t require high temperatures is radiation sterilization, aside from sterile filtration. For products that cannot be sterilized using heat or chemicals, radiation sterilization is a great substitute.
What things can radiation sterilize?
Items that can be sterilized by gaseous means are identical to those that can be disinfected by radiation. Plastics, heat-labile materials (such as electronics), and powders are common items and materials that are sterilized using radiation. Radiation is not advised for biologics since it destroys microorganisms’ nucleoproteins.
How are validations for radiation sterilization carried out?
Products are exposed to a specific radiation dosage in order to achieve radiation sterilization. The quantity and kinds of microorganisms on the product (product bioburden) determine this radiation dosage. As one might anticipate, microbial resistance to radiation sterilization is higher in populations with a higher bioburden, while it is lower in populations with a lower bioburden. Therefore, a higher radiation dose will be needed to sterilize a medical device or product with a higher bioburden. In contrast to the conventional overkill approach used with the majority of heat-based sterilizing techniques, sterilization validations for radiation employ a bioburden approach. Therefore, for products that will be sterilized by radiation, product bioburden control and monitoring are essential. It’s interesting to note that dosimetric measurements and product bioburden are more accurate than biological indicators when it comes to radiation sterilization validations. The following describes the actions taken and evaluated for validations of radiation sterilization.
The following tasks are evaluated in radiation sterilization process validations:
#1: Verification of Doses
To maintain the effectiveness of the sterilization cycle, analysts employ pre-sterilization bioburden controls and routine assessments of the impact of production processes on bioburden levels. The amount of radiation required to produce sterility may rise in response to increases in bacterial spore densities or bioburden. In fact, analysts can calculate a radiation dose that results in only one nonsterile unit in a million sterilized items due to the bioburden’s inherent radiation resistance levels and concentrations. The radiation dosage must coincide with the real bioburden of the products being sterilized during dosage verification.
#2: Compatibility of Product Materials
After establishing the minimum dosage required for sterility, analysts frequently calculate the maximum radiation dose by estimating the highest dose that a product is expected to receive during the radiation sterilization procedure. Materials are affected by radiation both immediately and over time. As a result, some materials may seem unaltered right after being exposed to radiation and then gradually decay. Material compatibility studies should assess the functionality of all radiation-exposed materials during the course of the product’s intended use. The most significant post-radiation risk for pharmaceutical items is the material compatibility of the medication product and its primary container.
#3: Qualification of Equipment
Software and equipment controls for gamma sterilization (and other radiation sterilization) systems must be evaluated both initially and on a regular basis. System timings, scan speed, and source intensity are a few examples of radiation sterilization system controls. Products are moved through the radiation sterilization cycle by a conveyor belt system found in the majority of radiation chambers. Equipment qualifications are therefore also necessary for machines that move goods.
#4: Dose Mapping in Empty Chambers
Radiation sterilization procedures can sometimes be validated without the need for empty chamber dose mapping. A helpful performance baseline for the radiation sterilization system is offered by open chamber dose mapping.
#5: Dose Mapping for the Entire Chamber (Load)
Finding the radiation dose distribution across the processed objects (load items) is the goal of load dose mapping. Products are placed in pallets, transporters, or containers after being sterilized. An item loading design that minimizes radiation dose fluctuation throughout the product’s materials is determined using load dose mapping. Dosimeters placed inside the load being sterilized (internally) and at key points throughout the radiation system (externally) are used to map sterilized objects. The location of the lowest and maximum dose exposures inside the radiation system and the group of sterilized goods can be determined using load dose mapping. Later, regular monitoring of the sterilizing process is supported by the dose mapping data.
#6: Verification of Dosimetry
Dosimetry is essential to radiation sterilization for both original development and continuous process verification. A local measurement of the radiation level in a specific region of the radiation sterilization system is provided by dosimeters. To keep dosimeters accurate, they need to be calibrated on a regular basis in accordance with ISO standards. Both for the first validation of sterilization and for regular management and monitoring of the sterilization process, dosimeter calibrations should be recorded.
#7: Verification of the Radiation Sterilization Process
Verifying the lethality of the radiation dosage received by the items processed through the radiation-sterilizing equipment is the main goal of sterilization validation. Replicating investigations that demonstrate the dosimetry results match the necessary minimum radiation value for sterility assurance is how sterilization cycle efficacy is achieved. These investigations also need to show that the sterilizing procedure does not exceed the maximum radiation exposure.
How are verified radiation sterilization procedures routinely monitored and controlled?
To retain validated status, controls for the radiation sterilization process need to be watched over and maintained. To ensure that radiation sterilization procedures continue to function efficiently, the following procedures must be followed:
Employee education
Calibration of dosimeters and equipment
Physical measurements and documentation of data
Monitoring of bioburden
Management of change control systems
Regular audits of radiation doses
Preventive maintenance and equipment qualification
Frequent mapping of load dosage
In brief
Overall, only a validated sterilization procedure following current good manufacturing principles (cGMP) can guarantee the sterility of medical products and devices. Validations of sterilization demonstrate that the sterility acceptance criteria, which are one unsterile product per million or less, are regularly fulfilled. A non-thermal sterilizing technique called radiation sterilization uses gamma radiation, beta particles (an electron beam), x-rays, or ultraviolet light to kill microorganisms in a product. Products and medical equipment that cannot resist heat or chemical sterilization techniques are sterilized by radiation. Dose verification, product material compatibility, dosimetry verification, and overall statistical confirmation of the sterilizing process are all activities that must be evaluated as part of radiation sterilization validations. In general, be sure the contract testing company you select can offer the proper sterilizing validations for your particular product or medical device requirements.
