Scientific Team / Validations
What is the main responsibility of the APH Scientific Team at the LA site?
Assay development and validation
Who is our biggest client in terms of validations?
AstraZeneca (AZ)
What is the goal of unstained slide stability studies?
Ultimately, we need to know whether the patient sample result is valid (is it within or outside the stability range?).
On a cellular level, where is LRRC15 located?
Membrane (transmembrane protein)
What general staining technique/special stain is used to differentiate cell nuclei and cytoplasm and to visualize morphology for pathologists?
H&E
What are LDTs and how do they differ from IVD kits?
Lab Developed Tests (LDTs) are created in-house, using commercial antibody concentrates, unlike IVD kits that are ready-to-use commercial products
What are the different types of validations we perform?
1st site/primary validations, 2nd site/secondary validations, addendums, Verification of Performances due reformulations, vendor discontinuations, etc.
What would accelerated unstained slide stability studies help with?
We could create earlier/preliminary unstained slide stability data -> this info could go into SOW much earlier.
What happens to LRRC15 in cancer?
LRRC15 is upregulated (high expression). It is upregulated in activated fibroblasts and mesenchymal stem cells, particularly in solid tumors such as breast, lung, pancreatic, and head and neck cancers.
In IHC, what molecule/protein binds specifically to the antigen in the tissue?
Antibody
Who approves all validations before the assay goes into production?
Dr. Yue
Despite some delayed validations, what is/was the status of the majority of the validations?
On target/finished on time!
How long are regular (real-time) stability studies?
12 months
Why is LRRC15 such a promising tumor biomarker?
Due to its association with upregulation in cancer and its link to poor prognosis in cancer.
Name at least 3 very commonly used IHC stains in our lab.
HER2, ER, PR, PD-L1, Ki-67, etc.
Aside from validation and Medical Director approval, what else needs to happen before assay can be used for patient testing?
Transfer of validated assay into production, including SOP creation and training of histotechnologists.
Aside from client-driven validations, what is the other type of validation we perform?
Strategic validation
Which is one of the markers that we used to demonstrated accelerated decrease of the antigenicity?
Ki-67
What type/category of assay are we validating for our sponsor Zai Lab?
LDT
What does FFPE stand for?
Formalin-fixed paraffine embedded
What are the key steps/activities for assay development and validation?
Validation plan, wet-lab experiments, pathologist reviews, and validation report.
How many different clients are there in terms of awarded validation projects (+/- 5)?
36
For accelerated stability studies, what are the conditions that we expose unstained slides to? (Hint: temperature and humidity)
37 °C and ≥80% humidity
What is the natural/normal function of LRRC15 in cells?
Membrane receptor and adhesion molecule (facilitates cell-cell and cell-matrix interactions, contributing to tissue structural integrity)
What is DAB?
3,3'-Diaminobenzidine. Brown chromogen to visualize the binding/detection of the antigen in the tissue.