Most single use devices are terminally sterilized by ethylene oxide gas, or gamma radiation, or electron beam radiation. The sterilization process must be present on the pre-sterilized product. By means of the cGMP medical device regulations, FDA has established some of the requirements for an acceptable sterility assurance program. More specific guidelines for validation of the sterilization processes are developed and published by AAMI in conjunction with ISO.
When auditors come to your facility to discuss sterilization requirements, they usually want to see two things: 1) the original validation package that determined what type of sterilization is best and what dose is appropriate (for radiation), and 2) review of periodic dose audits for the same product. An initial validation study usually takes 6 to 8 weeks, and is done on the largest container size in a series of the same material. That qualifies all sizes of that material to accept the same dose.
For gamma radiation, which we use for most of our products, there are several AAMI/ISO methods available to sterilize a medical device. All of these methods use product bioburden enumeration and a bioburden organism resistance test, which is referred to as the verification dose resistance experiment. The most appropriate methodology is selected based on the projected production schedule and size.
- AAMI/ISO 11137 Method 1 – For large and frequent production batches
- AAMI/ISO 13409 – For small production batches
- AAMI/ISO 15844 – For large but infrequent production batches
- AAMI/ISO VDmax – a new validation method which I use which is cheaper, and requires less samples
Initial validation costs upwards of $5,000, and periodic quarterly dose audits (or however often you make a production run) cost around $1,500. A dose audit is a sterility test of samples which have been irradiated at a defined kGy level determined as part of an AAMI dose validation study. Sterilization and reporting is usually around $1,000. These costs have to be included in your pricing, unless you have already validated the container/bottle. Chase only offers two I-Chem sizes as sterilized 400 series level products, since we had to have the containers validated, using the largest size, and we have to do a quarterly dose audit in accordance with AAMI/ISO guidelines. That becomes part of the pricing structure. We only run those quarterly, so we do a dose audit each time we do a production run.
If you have a defined kGy level for your containers, then someone must have commissioned an initial validation study, which you should have a copy of at EPSP. If you sell more than once, however, then you need to do quarterly dose audits, based on that initial validation report.