On April 26, 2019, CDRH released the final guidance, Recommended Content and Format of Non-Clinical Bench Performance Testing Information in Premarket Submissions (“Final Guidance”). We previously blogged on the draft version (“Draft Guidance”) here. Overall, the Final Guidance is much the same as the Draft Guidance, though FDA has added more detailed descriptions of the recommended information.
Like the Draft Guidance, the Final Guidance provides recommendations for Test Report Summaries and Complete Test Reports to be submitted in premarket submissions, including “premarket approval (PMA) applications, humanitarian device exemption (HDE) applications, premarket notification (510(k)) submissions, investigational device exemption (IDE) applications, and De Novo requests.” Final Guidance at 3. Test report summaries should include the following elements: tests performed; objective(s) of the test(s); a brief description of the test methods, including sample size, device(s), and any consensus standard(s) utilized; pre-defined pass/fail criteria (when applicable); results summary; discussion/conclusions; location of complete test report and summary table (optional). Complete test reports should include: test performed; objective of the test; description of test methods (test sample information, test sample size/selection, test methods); pass/fail criteria; data analysis plan; test results (data, data analysis, protocol deviations); and discussions/conclusions.
There are a few notable differences, first of which is the title. The Draft Guidance included “Complete Test Reports” in the title whereas the Final Guidance’s title covers “Information” more broadly than just complete test reports. That being said, the overall guidance does not broaden in scope and the name change appears a more appropriate description as the guidance covers both complete test reports and summary information included within a premarket submission.
The Final Guidance also adds clarity to several points, including:
- The recommendations are applicable for non-clinical testing performed by either a device manufacturer or a third-party testing facility.
- Bench tests using ex vivo, in vitro, and in situ animal or human tissue are within the scope of a non-clinical bench performance test. A new footnote is also added where FDA states their support of reducing, refining, and replacing animal testing when feasible and alternate methods are “suitable, adequate, validated, and feasible.” at 3.
- For testing excluded from the scope of the guidance, reprocessing validation, human factors validation, software verification and validation, and computational modeling studies are added in addition to biocompatibility evaluation and sterilization validation.
- Test report summaries should be provided either within an executive summary section of the premarket submission or provided as a separate document within the premarket submission. An example summary table has been added including columns for test performed, device description/sample size, test method/applicable standards, acceptance criteria, unexpected results/significant deviations, and results. Complete test reports, when submitted, should be provided as separate attachments.
- A complete test report means the “entirety of the testing documentation submitted for a study” which may be included in a single document or within multiple documents in the premarket submission. at 8.
- There are situations where pre-defined pass/fail criteria may not be applicable, such as tests conducted for characterization purposes. In these situations, a description of the acceptance criteria used to allow for interpretation of the data should still be provided.
- A data analysis plan used to analyze results, including all planned quantitative and/or qualitative assessments, is recommended in the test report.
- When recommended information comes from an FDA guidance document or FDA-recognized consensus standard, the full information can be replaced with the full reference to the cited document. If there are options or choices within the referenced document, the options selected or choices made should be included.
The Final Guidance no longer recommends including information in test reports justifying why the test methods or results support substantial equivalence. As we noted in the prior blog, the test report is not the place for this information as the connection between an engineering test and a planned 510(k) submission may not be known by an engineer performing testing and writing a test report. This information is certainly important within a 510(k) and the Final Guidance now more broadly states “[y]our premarket submission should also discuss how the non-clinical bench performance test results support the overall submission” and that the “information can be provided in the test report summary or another location in your premarket submission.” Id. at 5.
The Quality System Regulation (QSR), in 21 C.F.R. § 820.30 Design Controls, includes requirements for design verification and validation, yet these requirements are not mentioned anywhere within the guidance. While the Final Guidance may appear on its surface to provide a comprehensive list of information to include within “complete test reports,” it fails to identify some information required for verification and validation results by the QSR (e.g., the date, and the individual(s) performing the tests). Also, as we noted in the prior blog, the Final Guidance still recommends that test reports state whether the test sample is a final, finished device though this may not be known at the time many test reports are written during product development. With the recently announced CDRH reorganization and creation of a new Super Office, Office of Product Evaluation and Quality (OPEQ), we hope to see better alignment in the future between what is expected in a premarket submission and what is already required of device manufacturers in the QSR.
The Final Guidance may be helpful to companies in writing or revising their design controls procedures as it does provide useful descriptions of information to include within test reports. However, it is important to ensure the procedures cover QSR requirements as well as the recommendations of the guidance to ensure the resulting test reports are considered complete for both a premarket submission and in an FDA inspection.