A Push for Rigorous Regulation & Validation
In the United States, IVDs are regulated by the Food and Drug Administration (FDA) as medical devices under the Medical Device Amendments of 1976. This bill requires that manufacturers must submit studies confirming the test’s accuracy and usefulness in diagnosing a particular condition before bringing it to market1. In order to be cleared by the FDA, IVDs must demonstrate safety and effectiveness through both analytical and clinical validation. For analytics, the focus is on ensuring the test is correctly and reliably measuring a specified analyte. Whereas, for clinical validation, the focus is on determining whether it can accurately identify a particular clinical condition in a given patient2.
In European markets, including EU member states and EFTA states, IVDs are regulated by the In Vitro Diagnostic Regulation (IVDR) as of May 25, 2017. Beginning May 26, 2022 medical device manufacturers will be required to comply with the new IVDR in order to be placed in the European market6. With this new regulation, manufacturers will need to provide more rigorous clinical evidence including conducting more clinical performance studies and providing more evidence of safety and performance according to the device’s assigned risk class. Additionally, the IVDR will require more stringent documentation while implementing unique device identification for better traceability and recall6.
Biological Sequences: A Tool for Traceability in Patent & Commercial Applications for IVD
Although biological inventions do not require for the DNA or protein sequences to be disclosed, within the context of patent eligibility or infringement issues, their structure and function value is gaining more importance7. Further, the biological sequence information can provide an additional level of traceability and reproducibility.
Biological sequences are being viewed both legally and practically within patent applications, and as such, there are specific guidelines to follow. Notably, due to their function, biological sequences can only be determined with computer-aided technology; highlighting the importance of the sequences’ submitted format7. The most common format used is FASTA, which is a text-based format8.
Further, at the manufacturing level, there has been an industry push to hold vendors accountable to defining their antibody reagents based on unique identification numbers, known as Research Resource Identifiers (RRIDs). This will lead to a considerable increase in research traceability and reproducibility as scientists will be provided access to a database with information about what reagents to use and how they perform across systems, including original catalog numbers and vendor names.
Only 11% of landmark preclinical studies can be replicated
Although most of the reagents used in clinical trials cleared by the FDA or European Medicines Agency are considered reliable, due to the lack of industry regulation including quality control protocols, indefinite reproducibility remains to be a concern. This lack of vigilance has resulted in the widespread unintended use of cross-reactive antibodies, inaccurate data sets, and catastrophic waste of funds and time; ultimately significantly slowing progress in medical science9.
It is estimated that by 2019 global spending on antibodies rose to US$3.4 billion9, yet, one study suggests US$1.7 billion could have been wasted. Within this 2008 study, 6,000 commercial antibodies were tested and only half could successfully recognize their specified targets10. Further, within C. Glenn Begley’s study of 53 landmark preclinical studies, only 6 results were able to be replicated.