This presentation is a summary of the BABE Concept and Biowaiver which was prepared after the Seminar on BABE in KU, Nepal by Dr. Abhijeet.

1. BIOAVAILABILITY
BIOEQUIVALENCE
AND BIOWAIVER
Manoj Bhattarai
30th July 2018

2. BIOAVAILABILITY(BA)
• The rate and extent to which the active
ingredient or active moiety is absorbed from a
drug product and becomes available at the site of
action. (FDA 2003)
• Rate and extent of unchanged drug absorprtion.
• For drug products that are not intended to be
absorbed into the bloodstream, bioavailability
may be assessed by measurements intended to
reflect the rate and extent to which the active
ingredient or active moiety becomes available at
the site of action.
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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3. BIOAVAILABILITY (BA)
Depends on
• Pharmaceutical factors: Drug Substance and Drug
Product.
• Patient related factors: Age, sex, pathological
condition.
• Route of administration:
Parenteral>Oral>Rectal>Topical.
BA < Administered Dose.
Bioavailable fraction (F):
Bioavailable dose/Administered Dose.
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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4. Usefulness of BA Studies
 Selection of a dosage form for a new drug.
 Study of the influence of:
 Excipients
 Patient related factors
 Possible interaction with other drugs.
 Development of new formulations for an existing drug.
 Comparison between different brands of the same drug.
 Comparison between different dosage form of the same
drug.
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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5. BA STUDIES
• Subjects: Healthy Volunteers.
• Male adults (20-40 years) under restricted diet
and activity
• Female adults: Only for oral contraceptives
• Patients are also used in BA studies but only
after the success in healthy volunteers.
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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6. Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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7. MEASUREMENT OF BA
Pharmacokinetic Method
Indirect Method
• Plasma level time studies
• Urinary excretion studies
• Salivary excretion studies
• Bile and Cerebrospinal fluid
studies.
Pharmacodynamic Method
Direct Method
• Acute pharmacological
response
• Therapeutic response.
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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8. PARAMETERS FOR BA DETERMINATION
Cmax:
Indicates whether the
drug is sufficiently
absorbed.
Increases with the dose
and absorption rate
Tmax:
Indicates the rate of
absorption
Decreases with increase
in absorption.
AUC:
Measures the extent of
absorption.
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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9. PHARMACODYNAMIC METHOD
Acute Pharmacological
Response
• ECG, EEG, pupil diameter
• Construction of
pharmacological effect-
time curves, dose
response curves
• Measurement of
response at least for 3
half lives.
Therapeutic response
Method
• Measures effect on
disease
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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10. BIOEQUIVALENCE
• Absence of a significant difference in the rate and extent to
which the active ingredient or active moiety in
pharmaceutical equivalents or pharmaceutical alternatives
become available at the site of drug action when
administered at the same molar dose under similar conditions
in an appropriately designed study (21 CFR 320.1(e)).
• Studies to establish BE between two products are important
for certain formulation or manufacturing changes occurring
during the drug development and post-approval stages.
• In BE studies, the exposure profile of a test drug product is
compared to that of a reference drug product.
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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11. RELEVANT TERMINOLOGIES
Chemical Equivalent: Same API and Excipients
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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12. BE TEST METHODS
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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13. IN VIVO BE STUDIES
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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14. IN VITRO BE STUDIES
V. incase systemic availability-Parmacokinetics has been shown to be linear
over the therapeutic dose range.
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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15. BIOWAIVER
• A Biowaiver means that in vivo bioavailability
and/or bioequivalence studies may be waived
(not considered necessary for product
approval). Instead of conducting an expensive
and time consuming in vivo studies, a
dissolution test could be adopted as the
surrogate basis for the decision as to whether
the two pharmaceutical products are
equivalent.
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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16. Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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17. CONDITIONS FOR BIOWAIVERS
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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18. BCS CLASSIFICATION
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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19. BCS CLASSIFICATION
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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20. Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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21. Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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22. Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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23. Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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24. Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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25. Drugs Eligible for a
BCS-based Biowaiver
The following drug substances have been identified as eligible for a
BCS-based biowaiver application as either mono component or fixed-dose
combination (FDC) products:
Medicines for HIV/AIDS and related diseases
 Lamivudine (Class I)
 Stavudine (Class I)
 Zidovudine (Class I)
Anti-tuberculosis medicines
 Ethambutol (Class III/I)
 Isoniazid (Class III/I)
 Levofloxacin (Class I)
 Ofloxacin (Class I)
 Pyrazinamide (Class III/I)
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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26. Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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27. Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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28. Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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29. References:
• BABE Seminar by Dr. Abhijeet Gothoskar in
Kathmandu University, Dhulikhel, Nepal on
July 2018.
• WHO,EMA and FDA guidelines on BABE and
Biowaiver concept!
Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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30. Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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31. Manoj Bhattarai
Alive Pharmaceutical Pvt. Ltd.
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