Over the past 10 to 15 years, there has been a steady trend towards personalised medicine, particularly in the field of oncology. This has led to increased use of in vitro diagnostic products, or investigational IVDs, to determine the right medicine for the patient.
It is worth noting that personalised medicine is not a new concept and, in fact, dates back thousands of years to the Hippocratic period [1]. The arrival of epidemics, where patients reacted differently to diseases with the same symptoms, initiated the concept of personalisation of the disease, where the path through the illness varied according to the individual.
However, during the 18 centuries since the Hippocratic period, the concept of the patient as an individual gave way to a one-size-fits-all approach and resulted in a healthcare system that did not consider patients as individuals with different responses to disease [2].
From the 1950s, personalised medicine again gained traction and that trend has gained momentum in the last 20 years.
The advantage of a personalised approach is patients should expect to receive the right treatment for their type of cancer. The problem, however, is that the diagnostic might not always get the diagnosis right, meaning the patient is put on a treatment that won’t benefit them.
This creates a liability problem for in vitro diagnostics as well as a testing challenge. Because every patient is different, it may be that there is a right test but that the test carried out on the patient in question is not the right one.
FDA highlight concerns
The issues are well understood by regulators. The US Food and Drug Administration (FDA), for example, has raised concerns about the use of IVDs to guide the management of patients, stating: “use of an investigational IVD in a therapeutic product trial may pose significant risk to subjects. FDA is concerned that sponsors (including sponsor-investigators) and IRBs may not understand that many IVDs used as a critical part of therapeutic product trials are investigational.” [3]
The FDA has, therefore, issued guidance to support sponsors and investigational review boards when making determinations about the nature of risks of investigational IVDs used in therapeutic product studies. [4]
EU strengthens Regulations
Last year the EU introduced the In Vitro Diagnostic Regulation (IVDR), and more recently amended the transitional period to ensure high standards for safety and quality while also seeking to avoid market disruption. [5] The EU generated the European Parliament legislative resolution of 15 December 2021 on the proposal for a regulation of the European Parliament and of the Council amending Regulation (EU) 2017/746 as regards transitional provisions for certain in vitro diagnostic medical devices and deferred application of requirements for in-house devices (COM(2021)0627 – C9- 0381/2021 – 2021/0323(COD))
Setting the regulatory strategy
From an industry perspective, cost is a consideration, and more stringent guidance and regulation will have huge repercussions for the industry and for innovation.
To manage this complex situation, companies or innovators will need to define a gold standard for the type of indication. Once established and agreed with the regulatory authorities, they will have to conduct follow-up testing in order to demonstrate that their IVD is better, or more specific, than the gold standard. This will be guided by following the collation of clinical data.
Under these circumstances, the discovery of a new marker or IVD procedure, even if initially retained within an academic setting, demands market and regulatory consideration if it is going to be of any use in the near future.
Here, companies might turn to regulatory consultancy experts to support their approach. This might start with an evaluation of the market to define those standards using bibliography searches, reports and so on.
The challenge here is that many of these next-generation IVDs are developed in academic institutions, which rarely have expertise in turning great ideas into reality. Generally, these ideas would be sold to industry in order to bring them to fruition. However, IVD manufacturers are more hesitant about developing highly complex, highly specific products that would be expensive to bring to market and expensive to maintain on the market. This inevitably raises questions about innovation with IVDs and the risk to patients as well as the liability risks posed.
Finding a clear pathway
The shift from using IVDs to confirm a diagnosis to now using them to guide a diagnosis means manufacturers and regulators will need to find a pathway to ensure these products can continue to be used to support patients without making the cost of testing too onerous for the industry to withstand while ensuring patients have a diagnosis that meets the gold standard.
“When it comes to using IVDs (to guide treatment for personalised medicine) companies or innovators will need to define a gold standard for the type of indication and prepare a regulatory strategy to define its advantages.”
[1] Milestones in Personalized Medicine: From the Ancient Time to Nowadays-the Provocation of COVID-19, Visvikis-Siest, S. et al., Front Genet, Nov 2020, Sec. Genomic Medicine Volume 11 – 2020. https://pubmed.ncbi.nlm.nih.gov/33424917/
[2] Challenge of personalized health care: to what extent is medicine already individualized and what are the future trends? Fierz, W. (2004). Med. Sci. Monit. 10, 111–123. https://pubmed.ncbi.nlm.nih.gov/15114285/
[3] Investigational IVDs Used in Clinical Investigations of Therapeutic Products. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigational-ivds-used-clinical-investigations-therapeutic-products
[4] Investigational IVDs Used in Clinical Investigations of Therapeutic Products, 2017, FDA. https://www.fda.gov/media/109464/download
[5] Regulation (EU) 2022/112 of the European Parliament and of the Council of 25 January 2022 amending Regulation (EU) 2017/746 as regards transitional provisions for certain in vitro diagnostic medical devices and the deferred application of conditions for in-house devices. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=uriserv%3AOJ.L_.2022.019.01.0003.01.ENG