Biowaivers detail explanation topic .pdf

I am a pharmacist. These slides describe detail topic explanation biowaivers. I hope Pharmacy department students get more benefits about it.

1. Biowaivers
Dr. Muhammad Usman
Assistant Professor
IPS, UVAS, Lahore
[email protected]

2. Introduction
•The term “Biowaiver” is applied to regulatory
drug approval process when application is
approved based on evidences other than in-vivo
equivalence testing.
•BCS Classification system was introduced by
Department of Health and Human Services, US
FDA (HHS-FDA) with the aim to grant biowaiver
only to SUPACs(Scale Up and Post Approval Changes)but
application of biowaiver has been extended to
certain orally administered generic products.
Dr. Muhammad Usman 2

3. Introduction
•A Biowaiver means that in-vivo Bioavailability or
Bioequivalence studies may be waived (NOT
considered necessary for product approval).
•Only in-vitro testing (Dissolution) is performed
instead of conducting expensive and time
consuming in-vivo testing.
•The major advantage is the simplification and
reduction of time required for product approval
and availability to market.
Dr. Muhammad Usman 3

4. Biowaiver types of Products
•The FDA will waive the requirement for submission
of in vivo evidence demonstrating the bioavailability
of the drug product if the product meets one of the
following criteria.
1)The drug product is an IV solution and contains the
same API combined with same solvent and in same
concentration as in the IV solution that was approved
(NDA).
2)Topicallyapplied preparation.
3)Solid oral dosage form that is not intended to be
absorbed(e.gAntacids, Radiopaque medium etc.)
Specific in-vitrostudies may be required for example
BE of cholestyramine is performed in-vitroby binding
of bile acids to the resins.
Dr. Muhammad Usman 4

5. Biowaiver types of Products
4) Drug product is intended to be administered
through inhalationas a gas or vapor and
contains the same API in same dosage form as in
the product that was approved (NDA).
5) Oral solutions, elixir, syrup, tincture or similar
other solubilized form and contain no excipient
which can significantly affect the absorption of
active ingredient.
Dr. Muhammad Usman 5

6. 6) Lower strength of immediate release or
extended release products.
Dr. Muhammad Usman 6
Biowaiver types of Products
A
B
1000 mg
1000 mg
Bioequivalent
500 mg
500 mg
Biowaiver
A
B
250 mg
250 mg
A
B

7. BCS Classification
Dr. Muhammad Usman 7
High Solubility Low Solubility
High
Permeability
Class-I Class-II
Low
Permeability
Class-III Class-IV
Solubility:
A drug substance is considered highly soluble when the highest dose strength is
soluble in 250 mL or less of aqueous medium over the pH range 1–8.
BCS Based Biowaiver

8. •Permeability:
To be classified as highly permeable, a test drug should have an extent of absorption
>90% in humans.
1.in vivo intestinal perfusion studies in humans;
2.in vivo or in situ intestinal perfusion studies in animals;
3.in vitro permeation study using excised human or animal intestinal tissues
4.in vitro permeation study across a monolayer of cultured human intestinal cells.
•Dissolution:
An immediately release drug product is considered rapidly dissolving when not less
than 85% of the label amount of drug substance dissolves within 30 minutes using USP
Apparatus I at 100 rpm or Apparatus II at 50 rpm in a volume of 900 mL or less in each
of the following media:
(1)An acidic media such as 0.1 N HCl or simulated gastric fluid without enzymes,
(2)A pH 4.5 buffer,
(3)A pH 6.8 buffer or simulated intestinal fluid USP without enzymes.
Dr. Muhammad Usman 8

9. According to HHS-FDA
Dr. Muhammad Usman 9
BCS Based Biowaiver
Class I
BCS Class
According to WHO
Class I
Class II
Class III
If > 85% dissolved within 30
minutes at pH 1.2 to 6.8
(75 rpm)
If > 85% dissolved within 15
minutes at pH 1.2 to 6.8
(75 rpm)
BCS Class

10. Dr. Muhammad Usman 10
Other considerations for
Biowaiver
Rapidly
Dissolving
Must NOT
affect
absorption
of API
Must NOT
contain API
with Narrow
Therapeutic
Index
Product
should not be
designed to
be absorbed
from oral
cavity
Dissolution Excipients
Therapeutic
Index
Formulation