Navigating New FDA Guidance: Navigate BioPharma Prepares for the Future of Diagnostic Testing

Written by: Jennifer Griffith, Ph.D.

Due to new FDA guidance in 2024, organizations that create diagnostic tests in support of clinical trials have started down a new, four-year path. [1] In anticipation of this guidance, Navigate BioPharma had already begun to strategize and equip itself for stricter regulations for device developers. Since 1976, the FDA has provided oversight for Laboratory Developed Tests (LDTs), but that oversight has been less stringent than the more comprehensive requirements for In Vitro Diagnostic Devices (IVDDs). In the subsequent 50 years, however, the nature of LDTs has changed due to the development of more complex and powerful technologies. ?These LDTs also now play a greater role in patient decision-making. The need for more consistent reporting as the LDT landscape has evolved has prompted the FDA to enhance its oversight of LDTs, aligning it more closely with the robust controls in place for IVDDs. ?These changes will be incrementally implemented over the next four years, although the final version of requirements for assay categorization and control is not yet codified.

Navigate’s Director of GxP Development, William Bressler , notes, “the biggest shifts in requirements are in the areas of registration, design control, safety reporting, and assay validation, with the most significant being the upscaling of assay validations.” Assays primarily affected are those involved in patient decision-making and dosing. Exploratory diagnostics may be impacted by additional regulations in the future—those requirements are yet to be defined fully, but assays that guide medical decisions (e.g., treatment selection) are clearly within the scope of the FDA LDT ruling. As a result, technical experts must increase the rigor of assay validation procedures. Enter the key differentiator: documentation. New levels of and activities for compliance include a variety of outputs ranging from demonstration of good manufacturing practices to enhanced safety reporting to design control documents to health authority submissions. Quality Control processes, including Quality Management systems and oversight, add another layer of complexity and logistical coordination. Therefore, the FDA changes impact the entire organization—not just the lab.

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At Navigate BioPharma, our teams work together to meet these FDA IVD and EU IVDR (In Vitro Diagnostic Regulations) requirements for our partners. Our scientific experts perform their assay services and data analysis with diligence and excellence, and they also understand and execute writing tasks well. They are well-versed at creating assay work instructions, protocols, validation reports, and manufacturing documents to comply with both IVD and IVDR regulations and serve as key collaborators on compliance and regulatory tasks such as design documents, IDE (Investigational Device Exemption) applications (US), and PSA (Performance Study Application) submissions (EU). The success of our scientists’ efforts is greatly supported by subject matter experts (SMEs), optimized processes, and quality-controlled systems. Navigate employs a team of specialized Quality, Regulatory, and GxP SMEs who ensure that our procedures stay current and refined for maximum efficiency. We utilize MasterControl as our Quality Management System (QMS) for integrated document, training, and quality event management. The system allows us to host our Quality-controlled documents, to create a clear and streamlined workflow for document approval, and to assure timely access and compliance for document requests. Our project managers organize all these teams to maintain timelines and ensure swift communication. Developing and validating an assay under stricter FDA oversight requires experienced, knowledgeable team members from diverse functions to align on meeting higher level criteria to ensure successful health authority submissions under demanding deadlines. As Bressler notes, Navigate “has made the required transition to being able to fully support regulated IVD devices, both domestically and rest-of-world.”

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With the change in FDA guidance this year, many clinical research organizations are recognizing their need for a partner whose diagnostic tests and support services comply with the more stringent IVD requirements. [2] At Navigate, we have experience with regulated IVD devices for three of our four technology platforms: Ligand Binding, Genomics, and Digital Pathology. Our fourth platform, Flow Cytometry, will include a regulated IVD assay in 2025. Navigate is certified for ISO15189. Our Quality Management System is fully compliant with ISO13485, and we are preparing for the certification audit. Our QMS also meets the requirements of CFR 21 Parts 803, 809, 812, and 820. We have coordinated health authority submissions for the US, EU, China, and Japan (in process). By the end of 2024 alone, Navigate BioPharma will have submitted an IDE application in the US and PSA submissions in 10+ EU countries.

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Changes to align and strengthen standards for regulated LDTs and IVDs benefit patients by aggregating safety data and evaluating performance according to clear and unified standards. Bressler explains that these changes “increase the statistical power in monitoring of safety and other reportable events, which is a definite patient advantage.” As so many LDTs have progressed over the past 50 years, becoming de facto IVDs, the need for greater oversight has grown. Recently the EU and currently the FDA have upgraded their requirements for IVDs to ensure this oversight. [3] Navigate is well-positioned to support these improvements, benefiting patients as well as our customers as we move into the next four years.

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References:

[1] Federal Register :: Medical Devices; Laboratory Developed Tests https://www.federalregister.gov/documents/2024/05/06/2024-08935/medical-devices-laboratory-developed-tests

[2] Laboratory Developed Tests: Small Entity Compliance Guide | FDA https://www.fda.gov/regulatory-information/search-fda-guidance-documents/laboratory-developed-tests-small-entity-compliance-guide

[3] EUR-Lex - 02017R0746-20240709 - EN - EUR-Lex (europa.eu)

https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A02017R0746-20240709