FDA Urges Sponsors to Conduct Third Party Validations Prior to Submission – Since the start of 2024, there have been several high-profile cases in which unreliable, incorrect, and even fabricated data have been generated by third parties.  This includes, but has not been limited to, the manufacture of drug substance, drug product, clinical trial data collection, and clinical trial statistical results and output.  The FDA has urged Sponsors to carefully evaluate the third parties and to independently verify third party results before submitting to the FDA.  For over a decade, Facet has worked with Sponsors and third-party auditors to ensure support provided by partners meets or exceeds FDA requirements.  Facet’s strategic statisticians can provide important third-party validation of nonclinical and clinical trial results so that you can have confidence in the trial results and conclusions when you submit your final study reports.  If you have third party validation needs, contact Facet today!

Updates on FDA’s LDT proposed rule  – Results from laboratory developed tests (LDTs) provide physicians and patients with important health information on which medical decisions are made.  As a result, FDA and other stakeholders have argued that it is critical that the results of these tests are accurate and reliable.  Historically, LDTs have been regulated predominantly under the Clinical Laboratory Improvement Amendments (CLIA) of 1988, and to a lesser extent, under enforcement discretion by FDA under the Medical Device Amendments.  LDTs undergo CLIA certification (specific quality standards, and accuracy and reliability evaluations) and the Centers for Medicare and Medicaid Services (CMS) are responsible for CLIA certification enforcement.  In 2010, FDA expressed concerns that LTDs were becoming more widely used and complex.  A few noteworthy cases of unnecessary surgeries resulting from LDT inaccuracies (false positives for ovarian cancer blood markers as discussed in Miller et al., 2024) led FDA to argue that CLIA certification was no longer adequate to manage the risk to patients.  FDA urged Congress to give FDA sole authority (and financial support) to regulate LDTs.  In 2020, the Verifying Accurate, Leading-edge IVCT Development (VALID) Act was proposed to create a new, LDT- and IVD-specific regulatory framework, however, the VALID Act has yet to be passed by Congress.  In September 2023, FDA got tired of waiting and proposed a draft rule that LDTs and IVDs would be regulated as medical devices under the Federal Food, Drug, and Cosmetic Act.  The announcement was met with widespread regulatory, legal, financial, and practical criticism.  On March 21, 2024, these criticisms were further discussed in the House Energy and Commerce subcommittee hearing.  In an interesting stroke, notice was made public that the Office of Management and Budget received the draft final LDT rule on March 1 (prior to the subcommittee hearing), suggesting that FDA is done incorporating feedback and has moved to have to the final rule published.  If you have an LDT/IVD currently in use under CLIA certification or you are developing an LDT/IVD, contact Facet today to discuss how you can comply with FDA’s proposed (soon to be final) LDT rule.

Miller MB, Watts ML, Samuel L. FDA’s proposed rule for the regulation of laboratory-developed tests. J Clin Microbiol. 2024 Feb 14;62(2):e0148823. doi: 10.1128/jcm.01488-23. Epub 2024 Jan 11. PMID: 38206042; PMCID: PMC10865810.

FDA eSTAR for 513(G) Submissions  – The electronic Submission Template And Resource (eSTAR) is an interactive PDF form that facilitates the preparation of a complete medical device submission.  For some time, Sponsors have been required to use the eSTAR for 510(k) submissions (unless exempted), 510(k) combination product submissions, and Dual 510(k)/CLIA Waiver IVD submissions.  In fact, Facet was one of the first to use the eSTAR for a combination device-led application!  Use of the eSTAR has been and continues to be voluntary for De Novo, PMA, and Pre-Submissions.  For the first time ever, FDA is now encouraging (but not requiring) Sponsors to use the eSTAR for 513(g) requests for information.  Facet strongly encourages the use of the eSTAR whenever possible because it increases Sponsor efficiency through automation, ensures Sponsors prepare and submit a robust and complete application, and facilitates timely review by FDA.  Our experience with the eSTAR has led to important tips and tricks that can help you when you are preparing medical device submissions to FDA using the eSTAR.