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FDA minimal criteria: Diaceutics' opinion

8 Dec 2022

The concepts of precision medicine and personalized medicine date back to the 1990s when genetic information, environmental factors and lifestyle began to have an impact on the development of new drugs and their use instead of the usual one-drug-fits-all approach.

Diagnostic testing has always been fundamental to the precision medicine model as this is what enables physicians to select the most appropriate and optimal therapies based on a patient’s therapeutically actionable biomarkers. Today there are many successful stories of targeted therapies changing the landscape of cancer treatment with now well know biomarkers such as HER2, EGFR, BRCA, BRAF, PD-L1, ROS1, ALK, RET, MET, NTRK, etc.

Although many well-established companion diagnostic (CDx) tests, co-developed with therapies, have been approved by authorities, there are still challenges in the companion diagnostics application into routine practice.

In November 2022, The Center for Devices and Radiological Health (CDRH) launched a pilot program with the objective to move past the ‘one drug-one test’ situation and to introduce a concept of minimum performance criteria which allows physicians to order any test that meets those standards, instead of having to adhere to specific tests for a specific therapy. The minimum performance criteria are to be made publicly available in the clinical trial setup.

Choice of medicines available: image


The FDA announcement comes 1.5 years after the FDA initially released the industry guidance: Developing and Labeling In vitro Companion Diagnostic Devices for a Specific Group of Oncology Therapeutic Products.

Since introducing this guidance, the Group approval has been applied for:
1) Cobas EGFR Mutation Test v2
a. in NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations (plasma+tissue). Approved across 5 therapeutic products
2) FoundationOne
a. In melanoma whose tumors have BRAF V600E. Approved across 2 therapeutic products
b. In melanoma whose tumors have BRAF V600E and V600K. Approved across 3 combination treatments.
c. In NSCLC whose tumors have EGFR exon 19 deletions or exon 21 substitution mutations, NSCLC. Approved across 5 therapeutic products

The objective of the new initiative is to avoid patients undergoing multiple tests related to similar biomarkers adding complexity, cost and delays in the patient diagnostic pathway as well as potentially using valuable tissue which is increasingly becoming a limiting factor in patients receiving a timely and efficient diagnosis.


The FDA is also hoping this new initiative will lead to laboratories delivering more reliable tests.


Biomarkers associated with several targeted therapies include the famous breakthrough of immunotherapy targeting PD-1/PD-L1 shown below1). Many other targetable biomarkers or biomarker panel (including genetic and non-genetic) are under extensive research and show promising futures.


1) PD-L1 expression
a. Keytruda associated with PD-L1 IHC 22C3 pharmDx
b. Opdivo associated with PD-L1 IHC 28-8 pharmDx
c. Tecentriq associated with Ventana PD-L1 (SP142) and Ventana PD-LI (SP263)
d. Libtayo associated with PD-L1 IHC 22C3 pharmDx

Diaceutics opinion
Diaceutics, in collaboration with the Personalized Medicine Coalition (PMC) and a broad steering committee comprising of stakeholders across the pharma and diagnostic industry, laboratories and patient advocacy groups, conducted a study showing that nearly two thirds (64.4%) of newly diagnosed patients with advanced non-small cell lung cancer (aNSCLC) in the US did not receive the optimal treatment based on their genomic profile.


The results, published in JCO Precision Oncology: Impact of Clinical Practice Gaps on the Implementation of Personalized Medicine in Advanced Non–Small-Cell Lung Cancer, showed gaps in clinical practice across the patient’s diagnostic and treatment journey with just above 40% of patients being lost in steps related to test ordering, test performance and test reporting.

With approximately 30% of all FDA approvals (2018-2021) being precision medicine were therapies are dependent upon patients pretested to determine their eligibility and while the focus in precision medicine brings promise to patients, it has significantly increased the complexity in the patient diagnostic and treatment pathway.


Diaceutics believe a multi-stakeholder approach is needed to change the clinical practice and fulfil the promise of precision medicine. We believe the FDA initiative will support the ambition of allowing all patients access to a treatment optimal to them. The ‘1 drug - 1 test’ paradigm made sense in the early days of precision medicine but is now surpassed by the complexity in the market.


In our opinion the FDA pilot program of a ‘Minimum performance criteria’ will:

• Allow more flexibility to labs in choosing diagnostic assays applicable to their existing instrumentation
• Allow more flexibility to labs in choosing diagnostic assays applicable to their existing instrumentation
• Remove the need for understanding/deciding on therapy choice before choosing a specific diagnostic assay approved with the drug
• Support the labs relying on LDT options to obtain high quality outcome whether this is chosen due to financial reasons; insufficient reimbursement, no incentive to stock multiple assays for 1 biomarker, or practical reasons; lack of space for multiple instruments, lack of resources to educate and train on multiple assays for 1 biomarker etc.,

• Ease communication between treating HCP and Lab, directly or in MDT


However, the initiative raises several questions on how the program will work in practice:

• In the trial stage, how will the minimum performance criteria be secured across all sites? Who holds the responsibility to collect information, monitor, control and align on assay and methods? And at this early stage how will minimum criteria be established and secured?
• What requirements will FDA have on the minimum performance of assay standards? During trials and post launch.
• Will FDA require an IVD Class III (CDx) for initial/novel biomarkers and follow on assays can be IVD I?
• How and when will the minimal criteria be made public? Are there proprietary IP that will hinder the regulations to have an impact initially?

• Will it remove the Dx industries incentive to bring assays to market? The Dx providers today have an attractive business model catering for pharma’s need to develop a CDx in parallel with Rx development and FDA submission.
• Who and how will the quality of this broader use of assays be monitored? Especially antibody-based assays more sensitive to variability with changing parameters.

With a focus on every patient getting the opportunity to receive the right test and the right drug to treat their disease, Diaceutics are dedicated to supporting the stakeholders in precision medicine via our services and solutions.

With our unrivaled data repository and implementation services enabled by our diagnostic commercialization platform; DXRX – The Diagnostic Network® and our team of precision medicine experts we are uniquely positioned to solve commercialization challenges and drive solutions to unlock superior value from your Precision Medicine strategy.

The newly announced initiative from FDA, managed and implemented with the right support, is a step in the direction of bringing the right treatment to the right patient, releasing the potential of precision medicine short term, and laying the foundation for an even more complex future.

Innovations in diagnostic technology are disrupting the existing healthcare landscape, and patients are already benefitting from improved access to a range of cost-effective technologies. We are optimistic seeing FDA continue the promotion of personalized medicine and this latest regulatory reform will enable more patients to benefit from better testing and ultimately, better treatment.

We predict other enablers for fulfilling the promise of Precision Medicine will be:
• New technologies will continue to impact and drive precision medicine
• Finding patients earlier and referring them faster
• Meaningfully involve patients into their available treatment choices
• Appropriate reimbursement levels to be proportionate with the clinical value delivered
• Prioritized investment in diagnostic pathway
• Data to increasingly automate treatment decision support
• Labs increasingly partnering with physicians to inform their testing and treatment choices
• Platform business models, accelerate the pace of change as networks combine forces
• Automation, simplification and communication will be critical to ensuring these new technology arrivals find their rightful place and do not instead make the diagnostic pathway more complex than it already is

With a focus on every patient getting the opportunity to receive the right test and the right drug to treat their disease, Diaceutics are dedicated to supporting the stakeholders in precision medicine via our services and solutions. With our unrivaled data repository and implementation services enabled by our diagnostic commercialization platform; DXRX – The Diagnostic Network® and our team of precision medicine experts we are uniquely positioned to solve commercialization challenges and drive solutions to unlock superior value from your Precision Medicine strategy.

1) List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools) | FDA