Evaluation of quality and interchangeability of medicinal products - EAC/EC/WHO Training workshop /...

Evaluation of quality and interchangeability of medicinal products - EAC/EC/WHO Training workshop / 10-14 September 20071 |

Prequalification programme:Priority essential medicinesPrequalification programme:Priority essential medicines

Training Workshop for evaluators from National Medicines Regulatory Authorities in the East

African Community:

Evaluation of quality and interchangeability of medicinal

products.

Dar Es Salaam

United Republic of Tanzania

10 – 14 September 2007


Training Workshop on Evaluation of quality and interchangeability of medicinal products.

Training Workshop on Evaluation of quality and interchangeability of medicinal products.

Bioavailability versus bioequivalence

Presenter: Drs. J. Welink

Senior pharmacokineticist

Medicines Evaluation Board, NL

WHO adviser

E-mail: [email protected]


AbsorptionAbsorption

Pharmacokinetics

Describe the transport processes of drugs throughout the body


AbsorptionAbsorption

Pharmacokinetics

Use mathematical models to describe:

Absorption

Distribution

Metabolism

Excretion

dA/dt = dAa/dt – k.A


KineticsKinetics

The Kinetic Concept receptor

drug

effect


KineticsKinetics

The Kinetic Concept

receptor

drug concentration

effect

absorption distribution elimination


KineticsKinetics

The Kinetic Concept

absorption

dissolution

disintegration

bioavailability


BioavailabilityBioavailability

Bioavailability

Bioavailability describes the fraction of the

the dose of a drug that enters into

the systemic circulation.



Bioavailability

Bioavailability means the rate and extent to which

the active substance or therapeutic moiety is

absorbed from a pharmaceutical form and

becomes available at the site of action.

plasma



Evaluation of bioavailability in vivo:

• extent (and rate) of absorption

• relative bioavailability



oral / i.v. mass balance

extent of absorption



oral/i.v. absolute bioavailability

Estimates the efficiency of absorption of the drug from the formulation versus

an intravenous bolus injection

F = AUC oral / AUC iv



mass balance study

radio labeled drug

Recovery:

-expired air

-feaces -urine

Urine: intact = at least abs. bioavailability

Feaces: intact = may be not absorbed………



relative bioavailability

absolute bioequivalence

food-effect different formulations

interactions



Relative bioavailability food effect:

Time (h)

Plas

ma

Con

c. m

g/L

no change in absorption:

Time (h)

Pla

sma

Con

c. m

g/L

delay in absorption:

Time (h)

Pla

sma

Con

c. m

g/L

increase in absorption:

Time (h)

Pla

sma

Con

c. m

g/L

decrease in absorption:



Interactions:

Absorption

Distribution

Metabolism

Excretion

food effect

inhibition

protein-binding displacement

induction

decrease

increase



Plasma Conc.-Time curveimmediate/prolonged release

0

20

40

60

80

100

120

0 10 20 30 40 50 60 70

Time (h)

Pla

sm

a C

on

c. m

g/L

Plasma Conc.-Time curveprolonged release

0

20

40

60

80

100

120

0 10 20 30 40 50 60 70

Time (h)

Pla

sm

a C

on

c. m

g/L

Relative bioavailability diff. formulations:

Plasma Conc.-Time curvedelayed release

0

20

40

60

80

100

120

0 10 20 30 40 50 60 70

Time (h)

Pla

sm

a C

on

c. m

g/L


Bioequivalence Bioequivalence

Bioequivalence

Pharmaceutical equivalents:

Medicinal products are pharmaceutical equivalents if they contain the

same amount of the same active substance in the same dosage form

that meet the same or comparable standard.

Pharmaceutical alternatives:

Medicinal products are pharmaceutical alternatives if they contain the

same active moiety but differ in chemical form of that moiety or in the

dosage form or strength.



Bioequivalence

Bioavailability

Pharmaceutical equivalent

Pharmaceutical

alternatives



Bioequivalence:

Two medicinal products are bioequivalent if

they are pharmaceutical equivalents or alternatives

and if their bioavailabilities (rate and extent) after

administration in the same molar dose are similar

to such degree that their effects, with respect

to both efficacy and safety, will be

essential the same.



Essential similar products:

A proprietary medicinal product will be regarded as essential

similar to another product if it has the same qualitative and

quantitative composition in terms of active substances, and

the pharmaceutical form is the same and, where necessary,

bioequivalence with the first product has been demonstrated

by appropriate bioavailability studies carried out.



Bioequivalence:

= bioavailability with pre-defined criteria for the rate

and extent of absorption!!


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