To provide you with an idea of what we can do and which roles we are able to play in your projects, we would like to provide you with a quick glimpse into some of our previous work regarding diagnostic studies.
We do not disclose the names of our customers but will give as much information of our projects as contractually permitted. The list of our clients comprises the top ten of global players in IVD as well as major pharmaceutical companies. Annually, we conduct about 5 – 10 validations for IVD devices.
SARS-CoV‑2 / Influenza / RSV multiplex-assay validation
Large Chinese medical device companies (900 — 1300 employees) commissioned us with the clinical validation of lateral-flow and PCR-based multiplex assays that test for SARS-CoV‑2, influenza A, influenza B, and RSV, referred to as index tests in the following.
All index tests were designed as point-of-care products so the immediate testing after sampling had to be warranted. Because multiple pathogens were targeted by the index tests, a study design had to be developed that complied with EU Common Specifications 2022/1107 Annex XIII (common specifications for SARS-CoV‑2 testing devices) and the non-standardised requirements of influenza and RSV tests. For the latter two, statistical sample size calculation was conducted.
Moreover, because the studies were to be conducted during summertime in Europe, prevalence of the required pathogens was low.
Collaborations with suitable SARS-CoV‑2 test centres, hospitals, and doctors’ offices were established and ethical clearance for the studies was obtained. We chose a prospective clinical performance study design so the recruitment of donors at the point-of-care according to their symptoms was obligatory. Each patient donated individual swabs for index testing and reference testing. Index testing was conducted immediately after sampling. The swabs for reference testing were stored refrigerated and transported to the collaborating laboratory for qRT-PCR analysis within 24h. Additionally, due to the low prevalence of some target pathogens, retrospective sample sources had to be tapped to reach the desired sample size. This included sample collections in East Asia and challenging logistics to transport the samples safely to Germany for testing.
All study data was sorted, verified, evaluated, and archived by us. We generated the clinical performance study reports according to all applicable guidelines which were submitted to the customers together with the raw data. Notified bodies have not issued any complaints regarding the clinical performance data generated by us.
Layman study and usability assessment including minors
A Chinese medical device company with 500 employees required a layman study for the final validation of their lateral-flow SARS-CoV‑2 antigen rapid test, referred to as index test in the following. The index test was intended to be marketed in the EU and in China.
The study design needed to comply with the requirements of the EU and the NMPA, so both regulatory frameworks had to be integrated. Symptomatic individuals with unknown infection status had to be recruited as probands for the layman study.
The intended purpose of the device was altered repeatedly before the start of the study, which required multiple last-minute design changes. Particularly, the target population of the index test was expanded to include users below the age of 16 (i.e., minors). This meant that proband education and sampling procedures needed to be age-appropriate which required high organisational flexibility.
In accordance with EU and NMPA guidelines, the study was conducted prospectively with randomised donor inclusion. Two consecutive ethics votes were obtained, one for the initial study design with adult probands only, and an additional one for the inclusion of minors. Age-appropriate information forms were generated for each age-group.
A suitable self-testing environment was established at our company-owned study centre exclusively for lay user studies. Potential probands were recruited and supervised by trained personnel. Professional testing and lay user testing of each proband were conducted in parallel. Additionally, nasopharyngeal swabs were collected and sent to the collaborating medical laboratory for verification of the results by qRT-PCR.
For usability testing, questionnaires for user feedback collection and user observation were designed. Performance and usability data was appraised, evaluated, and reported according to all applicable guidelines.
A European pharmaceutical company required the development of an IVD product to stratify patients into responders and non-responders for the corresponding immunologic medicinal product. This included the prior identification of a suitable biomarker.
The extent of the project required efficient and transparent communication with multiple stakeholders that were specialised in the different fields of expertise. Our tasks included sample sourcing, analytical performance experiments, as well as the production of standardisation material. The regulatory framework of companion diagnostics (CDx) development and validation comprises both pharmaceutical and diagnostic regulations which had to be integrated and accounted for.
We conducted the complete procurement of clinical samples which included difficile ethical clearance and the generation and management of case report forms. The study required patients (75 % women) that were starting a therapy with one of three different therapeutics without having been under this kind of therapeutic agent before. Samples were collected before (t0) and during the treatment (after 10 – 14 weeks, t1; after 20 – 28 weeks, t2). A validation panel containing serum from patients with at least 15 different autoimmune diseases was produced to analyse the effect of possible interferences for the CDx. Quartets of serum, K3-EDTA‑, Na-citrate‑, and Li-heparin-plasma were collected from donors.
After identification of the biomarker, large-volume samples (500 ml) were required as standardisation material which were collected at our company-owned study centre in Hennigsdorf. Furthermore, we conducted stability experiments with the marker in our laboratory. The result of our work is a CDx medical device that will allow a personalised treatment of patients. Currently, the product is in authorisation phase.