Dissolution & Bioavailability Group

1. CCK Technical Groups – Session 1-A
Dissolution & Bioavailability Group
13 Jan 2019
Obaid Ali & Roohi B. Obaid

2. Reference:
Dissolution Method Development for Generic Drug Product
Banu Sizanli Zolnik, DOB, OPQ, CDER, FDA

3. To control consistency
To control the process
To assure the quality
Tool

4. Critical for formulation
development
Tool

5. To get waiver from bio-studies
Tool

6. To use as in-vitro
bioequivalence studies
Tool

7. Alcohol induced dose dumping
Tool

8. Post marketing approval
manufacturing change
Tool

9. Process Parameter
Material Attributes
Formulation Variables
Dissolution

10. Evaluation
Discrimination
Criteria
Method

11. Solubility
Apparatus
Media
Evaluation

12. Rotation speed
Sink conditions
Surfactant
Evaluation

13. Differentiates drug product
manufactured under target
conditions
VS
Formulation with meaningful
variations for the most relevant
manufacturing variablesDiscrimination

14. Particle Size
Clinical Batch
Multiple batches
Discrimination

15. Manufactured
product variants
with different
release
characteristics
1- Manufactured product variants with different release characteristics
1

16. Manufactured
product variants
with different
release
characteristics
Select optimal
dissolution
method with
adequate
discriminating
power
1
2
2- Select optimal dissolution method with adequate discriminating power

17. Manufactured
product variants
with different
release
characteristics
Select optimal
dissolution
method with
adequate
discriminating
power
Determine
bioavailability for
product variants
1
2
3- Determine bioavailability for product variants
3

18. Manufactured
product variants
with different
release
characteristics
Select optimal
dissolution
method with
adequate
discriminating
power
Determine
bioavailability for
product variants
Determine
dissolution rates
resulting in
similar in vivo
performance
1
2
4- Determine dissolution rates resulting in similar in vivo performance
3
4

19. Manufactured
product variants
with different
release
characteristics
Select optimal
dissolution
method with
adequate
discriminating
power
Determine
bioavailability for
product variants
Determine
dissolution rates
resulting in
similar in vivo
performance
Dissolution
specifications
chosen to ensure
similar (BE)
product
performance1
2
5- Dissolution specifications chosen to ensure similar (BE) product performance
3
4
5

20. Manufactured
product variants
with different
release
characteristics
Select optimal
dissolution
method with
adequate
discriminating
power
Determine
bioavailability for
product variants
Determine
dissolution rates
resulting in
similar in vivo
performance
Dissolution
specifications
chosen to ensure
similar (BE)
product
performance
Illustration of
dissolution profile
based on BE
batches/ reference
1
2
6- Illustration of dissolution profile based on BE batches/ reference
3
4
5
6

21. BE batches
85%
drug is dissolved
Time
Q = 80% of drug
Criteria

22. Application is not supported
with dissolution method
development data
Common Deficiencies

23. Failed to demonstrate that the
dissolution method is
discriminating
Information on critical material
attributes & process parameters
are missing
Common Deficiencies

24. Data do not support the
proposed acceptance criteria
Common Deficiencies

25. There is no dissolution data for
the lower strength waiver
Multi media testing for MR
products
Common Deficiencies

26. Method transfer report is not
available when method
validation is done at different
sites
Common Deficiencies

27. Dissolution data collected on
aged lots
Common Deficiencies

28. Individual dissolution data is
not submitted
Common Deficiencies

29. Remember
Dissolution method is product specific, nothing
cannot be assumed, everything has to be justified

30. Thanks