Bioequivalence study Training - PowerPoint Presentation

Slide1

Bioequivalence studyTraining

Date: May 2016

Pharmaceutical

Product

Marketing

2BE is the most important requirement for the approval of GENERICS.to provide a safe and effective product for doctors and patients for the claim to act as a therapeutic equivalent compared to a reference product (innovator brand formulation/originator).for the permission of substitution with the full expectation of

the

same clinical effects, safety profile and tolerability

as the innovator´s product.

Bioequivalence (BE) study

3Bioavailability (BA): Rate and extent to which a drug is absorbed from a pharmaceutical formulation and becomes available at the site of action (e.g. bloodstream).Bioequivalence:This term describes preparations of the same drug which display same/comparable BA.Bioequivalence is assessed by comparing the BA of a test formulation to a reference product and is studied under similar experimental conditions.Bioequivalence (BE) study

4Example of Panto-Denk similar conditions for both:- Single doses- Same route of administration- Fasting conditions- Volunteers (male adults, 18-45 years, body mass index 19-29 kg/m2)- According to the European BE-guidelines and Good Clinical Practice- Randomized, etc. …

Originator

b

rand product

Generic drug

Bioavailabilities

(here nearly identical)

T

here

is no significant difference in their

bioavailability!

Bioequivalence (BE) study

5When bioavailability is the same, two formulations are said to be “bioequivalent”. That means they are expected to produce the same clinical effectsame safety profile and same tolerability.

Our bioequivalence studies prove that our

Denk

-products are bioequivalent to the originator brand

.

Doctors and pharmacists may substitute the more expensive product.

Bioequivalence (BE) study

6For the permission of substitution a Generic product has to be proven as bioequivalent to the innovator reference!Generic products have to be approved as bioequivalent to the originator product according to international acceptance criteria and standards (guidelines for industry EMA/FDA).

Bioequivalence (BE) study

7Bioequivalence (BE) studyBioavailabilityRate and extent to which a drug from a pharmaceutical formulation reaches the blood circulation.Intravenous administrationBioavailability: always 100%Oral administrationBioavailability: depending on formulation and absorption

Time

In oral solid formulations the absorption depends on excipients and manufacturing processes.

As bioavailability of IV injections is always 100%

no BE study is needed

.

e.g.

Grani-Denk

,

Zoledro-Denk

…

8Bioequivalence (BE) studyHow a bioequivalence (BE) study is conducted:Each subject is given a dose of the product (either the brand-name or generic drug), and blood samples are drawn at carefully chosen time points and analyzed for drug concentration. From this data, the basic pharmakokinetic parameters (AUC, Cmax, etc.) are calculated and compared between the innovator brand-product and generic versions. AUC (area under the curve) refers to the “total drug exposure” and Cmax to the peak concentration of the drug.Conducting a BE study is the most expensive step of generic drug development!

Acceptance criteria

2 formulations are bioequivalent if

90 %

of the ratios

are in the range from

80 %

to

125 %.

9Why is a bioequivalence study (BE study) conducted?2) How is the term bioequivalence defined?3) When looking at two bioequivalent drugs, which properties are the same?4) Why is there no BE study for I.V. injections?5) What are the acceptance criteria for bioequivalence?Train your brain – Quiz!

101) Why is a bioequivalence study (BE study) conducted?It is needed for approval of generic pharmaceutical products and provides permission for substitution.2) How is the term bioequivalence defined? Preparations of the same drug that show the same/comparable bioavailability. (FDA: “Bioequivalence means the 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…”)

3) When looking at two bioequivalent drugs, which properties are expected to be the same?

The therapeutic equivalent: Clinical effect, safety profile, tolerability, GMP produced, etc…

4) Why is there no BE study for I.V. injections? Bioavailability is always 100 % for I.V. injections

, because bioavailability is defined as “rate and extent to which a drug reaches the blood circulation” and both injections are directly administered into the veins. I.M. injections on the other hand do need a BE study as they need to be absorbed from the muscle to the blood stream first.

5) What are the acceptance criteria for bioequivalence?

90 % of the ratios in a range from 80 % to 125 %.

Train your brain

12Appendix - Bioequivalence (BE) studyBackground:The pharmaceutical industry is ever exerted to satisfy patient’s therapeutical needs and apart from active ingredients, inactive excipients play a major role in formulation development. Diluents, fillers, binders, disintegrants, lubricants, glidants, coloring agents, preservatives, coating and flavor agents are technically "inactive" from a therapeutic sense.However pharmaceutical excipients and different manufacturing processes (e.g. direct tableting vs. granulating) may be critical and might change the release mechanism, rate and extent of absorption and with this the BA of a product.Sometimes it is necessary to compare common alternatives, e.g. tablets vs. capsules, or active ingredient with its esters or another salt.