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Case Examples

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 

Back­ground:

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.

Chal­lenges:

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.

Exe­cu­tion:

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.

Back­ground:

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.

Chal­lenges:

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.

Exe­cu­tion:

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.

Back­ground:

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.

Chal­lenges:

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.

Exe­cu­tion:

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.

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in.vent Diagnostica GmbH

Neuendorfstraße 17
16761 Hennigsdorf

P: +49 (0) 3302 55199-550
F: +49 (0) 3302 55199-999

Mail: ics@inventdiagnostica.de