Biomarker and Companion Diagnostics in medicinal products registration process: a bridge between the pharmaceutical and device worlds. Defining the right quality strategy considering the different phases of drug development: from research to phase III clinical trials

In recent years, medical advances in therapeutics and diagnostics have shed light on new aspects of clinical practice, laying the foundations for the so-called “personalized medicine” which uses molecular profiling to identify the most appropriate treatment strategy for the right person at the right time or to identify a predisposition to certain diseases enabling targeted and timely prevention. In many cases, the resulting treatment is based on predictive biomarkers which are a fundamental part of drug development process, as they could help to comprehend and define the disease biology. They are linked to new therapeutic approaches, being a differentiator of that new therapy in the marketplace. Biomarkers can also reveal the pathogenic processes or pharmacologic responses to a therapeutic intervention and in this case, they require a Companion Diagnostic (CDx). CDx are a particular class of In Vitro Diagnostic (IVD) coupled with a therapeutic drug and aimed at assessing its applicability to a specific class of patients selecting those individuals who can benefit more from a certain treatment and with a lower risk. When a CDx is developed there is also a parallel development of the novel therapy as well as the biomarker-based assay. However, over the years there’s a variety of factors that are critical for the success of drug and CDx development. An early engagement and discussion with pharma companies, with the diagnostic partners and with the service providers to select the right assay and the right platforms should be an integral part of the development strategy. For these reasons, considering the significant role that CDx play in the clinical use of biomarkers, their development, validation, manufacturing, and distribution processes must be tightly regulated. From May 2022 a new EU Regulation has become effective to increase the requirements for IVD and CDx: Regulation EU 2017/746 of the European Parliament (IVDR) which repeals the previous Directive revolutionizing the IVD market. The new IVDR provides for different new features with more stringent conformity assessment procedures and increased obligations for both manufactures and notified bodies, which are the entities authorized to certify products based on specific procedures. At the same time, since CDx are coupled with a specific drug, their production and development must also be done in accordance with GxP (Good x Practices) quality guidelines to ensure the product is safe and meets its intended use. Guidance documents from several regulatory agencies, as the EU IVDR, have attempted to outline the steps in the CDx creation and the complexity of the drug–diagnostic co-development process. However, the lack of a standardized framework that bridges CDx guidelines compliance with GxP principles during the co-development process still represent a critical research gap in this field. For these reasons, considering the increasing complexity introduced by the new IVDR and its integration with the GxP principles, the aim of the project is to define the right quality strategy for the identified biomarker candidate and the corresponding CDx and then for CDx development considering the GxP regulation in the pharma context and the IVD requirements in the device context. In particular, the first year has been dedicated to the learning of the GxP, to the deepening of the knowledge of CDx/IVD regulations, of the main biomarker and CDx platforms and of the quality principles, under the supervision of the company tutor. Studying the proposed material, together with attending to company meeting, a satisfactory basic knowledge of the topic, fundamental to the development of the project in the successive years, has been reached. The second year, instead, has been devoted to the issue and adaptation of a quality strategy proposal, while the third year has been used to evaluate results of the quality strategy definition that has been formalized in an internal document