Since the EU IVDR came into effect in May 2022, Discovery’s clinical laboratory in Kassel, Germany has supported 40 biopharma client projects under Health Institution (HI) status, with zero Performance Study filings required. That track record, built over four years, translates to an estimated $300,000 or more in savings per project and months shaved off clinical trial startup timelines. Our Kassel facility is one of the few CRO labs in the EU recognized by local authorities as a qualified Health Institution, a status that enables us to deploy lab-developed tests (LDTs) under the IVDR 5(5) exemption and bypass the Performance Study Application (PSA) process entirely.
Under EU IVDR requirements, a device should be CE-IVD if it is to be used for any medical purpose in a clinical trial. This is often difficult to support for 1) novel therapeutics requiring a precision diagnostic, as novel biomarkers will most often not have a CE-IVD kit available; or 2) label expansions for existing therapeutics, which may fall outside of the instructions for use of the CE-IVD kit (e.g., new indication, new cutoff, etc.). If there are no CE-IVD devices available to support patient enrollment in a clinical trial, two options are available. The first is a Performance Study Application (PSA) as part of the pharma client’s regional clinical trial applications. The PSA must be provided to the competent authority in each member country prior to initiation of clinical sample testing, and review times, translations, and other activities can readily add from 90 to more than 200 days in addition to analytical validation of the assay (reference). The second option is to deploy a lab developed test (LDT) as a health institution under the IVDR 5(5) exemption. This eliminates the need for the PSA filing and can shorten time to first patient sample by 3 months to 6 months. Discovery’s clinical laboratory, located in Kassel Germany, is qualified as a Health Institution and is uniquely positioned amongst CROs in that it can provide testing using both in-house devices and novel devices using the Performance Study Application pathway. This approach is not permitted to the vast majority of CROs, as the facility must be located in an EU member country to be eligible for Health Institution status.
We have an excellent scientific team at Kassel, Germany and all of our LDTs are validated fit-for-purpose based on CLSI standards. This includes preparation of a full Design History File according to Annex I IVDR and associated regulatory requirements. In general, the laboratory can develop a novel biomarker clinical trial assay within 6 to 8 months, or 5 to 6 months to re-purpose an existing CE-IVD kit for new applications. Since IVDR has come into effect May 2022, our experience can be summarized as follows:
By the Numbers: Four Years of Health Institution testing
- We have supported 40 client projects that utilized our Health Institution status to support prospective clinical testing
- A total of 30 different biopharma clients.
- More than 22 different biomarkers, with approximately 60% of all projects being development of novel biomarkers (and the others being deployment of the “usual suspects” such as HER2, PDL1, KRAS, etc. for new applications)
- Clinical trials based in 22 EU member states and the UK
- Multiple technologies:
| Methodology | Count | Percentage |
| FISH | 9 | 23% |
| IHC | 20 | 50% |
| NGS | 1 | 3% |
| PCR | 9 | 23% |
| Sanger Sequencing | 1 | 3% |
The preponderance of IHC in the list above is largely driven by industry focus on development of antibody drug conjugates, bispecifics, and other drug classes that target membrane expression of tumor proteins and antigens.
One important note is that as a Health Institution, we do not have direct contact with regulators in each individual member state. We rely on the pharma sponsor of the clinical trial application to inform us if there are any further requests from regulators for clarifications. Our working model is that no news is good news, and to date we have not received any feedback beyond requests for additional information or documentation. No requests for further analytical validation, and no requests for a full Performance Study.
In conclusion, we have gathered significant experience utilizing our Health Institution status to get new biomarker tests into the clinic quickly and inexpensively. While there continues to be the perception this is a high-risk approach, our experiences do not align with this concern, and we see the use of LDTs performed at a Health Institution as a valid alternative to the more burdensome and costly PSA. For every project we have supported, we have likely saved the client at least $300,000 to support PSA filings, and potentially millions more preventing delays in clinical trial startup in the EU (estimating a $1 million per month burn rate for a typical development-stage biopharma sponsor). On balance, it is possible to save both time and money while keeping regulatory risk low.
T. Scott Reid
Scott Reid is Vice President and Global Head of Companion Diagnostics for Discovery Life Sciences. He has spent many years in the diagnostics and laboratory services industry, including SOPHiA Genetics, NeoGenomics Laboratories, Laboratory Corporation of America. His focus is development of precision diagnostics tools to help enable clinical trials, especially with regards to companion diagnostic development and commercialization. Scott holds a PhD in Biochemistry and an MBA from Duke University.
