510k submissions

This article explains the process for preparing the sterilization validation and shelf-life section of a 510k submission.

Sterilization validation and shelf-life, Section 14, is typically one of the last sections of a 510k submission to be completed. However, most of the work in preparing this section of your 510k submission should be completed more than a month before actually completing the associated testing. The reason why you can write this section, before receiving the results, is that your results are 99% predictable. If you are unlucky enough to be part of the 1% that have surprising results during sterilization validation, then you will need to make changes and repeat your testing.

Design Planning Aspects Related to Sterilization Validation

During your design and development process, sterilization validation testing is part of design verification testing—not design validation. This testing is verification, rather than validation because you are testing in accordance with recognized standards (i.e., design inputs) to ensure that the sterilization process parameters are adequate to consistently meet the sterility specification (i.e., design output). In your design plan, it is critical to understand which of the following three categories your sterilization process falls under:

1. Traditional Sterilization (e.g., ethylene oxide)
2. Non-traditional Sterilization (e.g., Hydrogen Peroxide)
3. Novel, Non-traditional Sterilization (e.g., Chlorine Dioxide)

You must identify which category your sterilization process falls into because the review process used by the FDA for each category of the sterilization process is different. Traditional sterilization processes have recognized standards that a reviewer can easily compare your validation methods with.

Non-traditional sterilization methods are becoming more popular for products that are sensitive to degradation caused by high temperature, or exposure to radiation or ethylene oxide. However, the FDA has identified non-traditional sterilization processes as being a priority for inspection. Therefore, after your product receives 510k clearance, you can expect an FDA inspection sooner than products that use traditional sterilization methods (i.e., 6-12 months instead of 12-24 months). 

The novel, Non-Traditional Sterilization

The novel, non-traditional sterilization methods require a different 510k clearance process, because the FDA requires an internal consultation from the Infection Control Devices Branch (INCB) before issuing 510k clearance. A consultation is needed for evaluation of the sterilization process because reviewers lack sufficient expertise in the field of microbiology and Sterilization to evaluate novel sterilization processes. The INCB can also provide a consult for non-traditional sterilization processes, but this is not typically needed if the process is following established ISO Standards for sterilization validation. 

For the novel, non-traditional sterilization processes, and INCB consult is required, and it is recommended to consult with the FDA early regarding the use of this type of sterilization process. Part of the reason for this early consultation is that a pre-clearance priority inspection is required before issuing the 510k. The FDA published draft guidance on this topic in 2008 that can be found on the following webpage – Click Here.

The image below shows where the INCB is located within the hierarchy of the FDA’s organization.

Creating Summary Technical Documentation (STED)

The sterilization validation and shelf-life section of a 510k submission may be copied from the summary technical documentation (STED) that you prepare for CE Marking applications or a Canadian Medical Device License Application. Instead of including all of the protocols and testing reports from your validations, the regulators only require a summary of the validation activities and results. If the STED is thorough and well-organized, the reviewer should not request validation reports. However, if the STED is incomplete, then the reviewer is likely to request a copy of the validation reports.

Any STED should include the following elements:

1. Identification of the validation dates
2. Identification of the organization(s) that performed the validation
3. Reference to the ISO standard or other recognized standard that was used
4. Identification of any deviations from the referenced standard
5. Number of lots and samples per lot tested
6. Description of the testing performed—including testing parameters
7. Identification of the document control numbers and revisions for protocols and reports
8. Acceptance criteria for the validation
9. Summary of the results

For your STED specific to sterilization validation and shelf-life, you will also need to ensure you include a description of the packaging used to maintain the device’s sterility (primary packaging) and a description of the packaging used to protect the primary packaging (i.e., secondary packaging).

For a 510k submission, you will only need to make a few modifications to the STED that you use for European CE Marking and Canadian licensing. First, you need to ensure you are referencing standards recognized by the FDA. If you followed a different method, the differences need to be documented in Section 9 of your submission on FDA Form 3654 for each Standard.

Second, you will need to include a reference to Ethylene Oxide (EO) residual testing summarized in Section 15 for biocompatibility (not applicable to non-EO methods of Sterilization). EO residual testing must be performed in accordance with ISO 10993-7. You should also include an outline of the validation methods that were used in your comparison of substantial equivalence in Section 12 of your submission. Finally, you should reference the methods used briefly in your executive summary (i.e., Section 10) and the 510k summary (i.e., Section 5)—assuming that you did not use a 510k statement.

If you are writing your first STED for sterilization validation and shelf-life, I recommend reviewing the RTA checklist in advance.

You may want to organize your STED with headlines that address each of the questions outlined in the RTA checklist.

You should also be aware that although the FDA references the 2002 guidance document K90-1 for the format and content of the sterilization validation section, there is a 2008 draft guidance the represents the FDA’s current thinking on the topic of sterilization validation. That draft guidance document is also identified as a priority for the FDA to release as a final guidance in FY 2015 (i.e., before October 1, 2015).

Additional 510k Training

The new 510k book, “How to Prepare Your 510k in 100 Days,” ships on Monday, February 6th, 2017. There is also an on-line 510k course series consisting of 24 webinars. Please visit my webinar page to purchase individual webinars. We also have live 510k workshops