An academic talk

1. Track, Trace & Understand
Science of Life from Real world Evidence
Obaid Ali, R.Ph., Ph.D.
Chief Scientific Officer, CQS
9th Annual Neuroscience Conference IBRO – APRC – University of Karachi - 13th August 2023

2. Key Reference of talk: US-FDA

3. Key medical product development
tool capable of facilitating
development and innovation.
Biomarkers

4. Characteristic that is measured as an
indicator of
• Normal biological process
• Pathological process
• Response to an exposure …
• Response to an intervention …
Biomarkers

5. Types
• Histologic characteristics
• Radiographic characteristics
• Molecular characteristics
• Physiological characteristics
Biomarkers

6. Categories
1. Susceptibility
2. Diagnostic
3. Monitoring
4. Prognostic
5. Predictive
6. Pharmacodynamics
7. Safety
Biomarkers
Description
A. Name
B. Source
C. Measurable characteristic
D. Analytical method

7. Valuable information may reduce
uncertainty in regulatory decisions
Qualified & approved for stated
context of use (COU)
Biomarkers
Development of Drug

8. • Collaborative process
• Shared resources
• Reduce burden
• Working in consortium
• Encourage knowledge sharing
Biomarkers
Qualification
Qualified biomarker does not mean qualification of biomarker measurement method

9. COU
• LOI
• QP
• FQP
Approved or not approved
Biomarkers Qualification
Process

10. • Letter of Intent
• Provides initial information
• Shares context of use
• How biomarker will be measured?
FDA … values to address unmet drug
development needs and overall proposal
feasibility based on current scientific
understanding
What is LOI

11. • Qualification Plan
• Proposed biomarker development plan
• Focus on COU in drug development
• Identify knowledge gaps
• Proposed opportunity to fill the gaps
• Detailed analytical method
FDA accept and may ask for Full
Qualification Package
What is QP

12. • Full Qualification Package
• Supporting evidence for biomarker
and COU
• All accumulated information
organized by topic area
FDA will make final decision based FQP
for COU and use in regulatory approval
of new drug
What is FQP

13. • Improved diagnosis of disease
• Predict future disease severity
• Predict prognosis
• E.g. blood pressure for CVS, sugar for Diabetes.
❑ Improved understanding of impact of tobacco products
❑ Effectiveness of medical treatment or device
❑ Bridging non-clinical research to clinical research
Significance of
Biomarkers

14. 4-(methyl nitrosamino)-1-(3-pyridyl)-1-
butanol (NNAL)
• Tobacco exposure
• Informative for assessing potential
health risk of tobacco product
Example

15. • Immune corelates – for effectiveness of
vaccine
• Sensitive marker for drug induced
cardiac injury
• Sensitive marker for drug induced
liver injury
• In vitro and in vivo test for assessing of
treatment induced genetic damage
Example

16. • Patient reaction to metal implants
• Susceptibility to hypersensitivity
• Chronic immune response
• Advance and promote device safety
Example

17. 2016 - Prognostic biomarker to predict rate
of loss of kidney function in orphan
disease
Surrogate endpoint considered for
accelerated approval, shortening the
required duration and size of Phase III
trial.
TKV
Total Kidney Volume

18. 2016 - Plasma biomarker as assessed by
immunoassay
Prognostic biomarker used with other
characteristics to enrich for Chronic
Obstructive Pulmonary Disease (COPD)
exacerbations for inclusion in
interventional clinical trials
Fibrinogen

19. 2012 - Serum/plasma cardiotoxicity
biomarkers as assessed by immunoassay
Safety biomarker to indicate cardiotoxicity
in rats, dogs or monkeys when testing
known cardiotoxic drugs and may be used
to help estimate non-toxic human dose
Cardiac troponins
T (cTnT) & I (cTnI)

20. Analyzing new measures of tumor
response and progression developed
specifically for cancer immunotherapies
through pooled analyses of oncological
clinical trial data
Designed to capture atypical response seen
with immunotherapies (tumor size
followed by tumor burden) … infancy stage
iRECIST

21. Thanks