Bioequivalence

Question 1

Generic Drug Products

Answer 1

Copies of brand name drugs with same active ingredient and same intended therapeutic use as the innovator product.

They look different from the innovator product and are cheaper

Question 2

When and Why were regulations on generic drugs instituted?

Answer 2

1962

Products with the same amount of active ingredients were giving different therapeutic responses - mostly due to dissimilar Cp vs t, resulting in impaired absorption and fraction of drug absorbed (F).

There was also increasing efforts to define BA and BE and produce assessment procedures

Question 3

What was the Thalidomide tragedy? What was the result in terms of drug regulations?

Answer 3

drug to cure morning sickness in late 1950’s

found to be cause of birth defects (phocomelia - poor limb development, deaf, blind, disfigure, cleft palate etc.)

withdrawn from market 1961

prior to 1962 drugs approved only on basis of safety - new regulations were drafted under the food, drug, and cosmetic act

Question 4

Drug amendments of 1962

Answer 4

• proof of efficacy requirement NDA
• generics must meet safety, efficacy, BE criteria
• resulted in decreased generic production

Question 5

Classifications of Fraction of Drug absorbed (F) and BE

Answer 5

• factors affecting dissolution or release of drug from dosage form
• factors related to excipients that may affect stability, absorption, or metabolism

Question 6

Which act was instituted in 1984?

Answer 6

Drug price competition and patent term restoration act aka Hatch-Waxman Act

Question 7

What was the Hatch-Waxman Act?

Answer 7

The Drug Price Competition and Patent Restoration Act

• established abbreviated new drug application procedure (ANDA), which approved generics of drugs considered safe and effective
• • generics must meet pharmaceutical equivalence and BE
• • role in drug discovery and development - BE relates directly to safety and efficacy

Question 8

What are the benefits of the Hatch-Waxman Act to Society?

Answer 8

pharmaceutical industry, health care practitioners, and the general public benefit

• increased availability of generics, decreased costs of health care
• pharmacist plays key role - product selection, what is best for the patient, communication pipeline

Question 9

What is the goal of BE testing?

Answer 9

-determine if two pharmaceutically equivalent drugs are interchangeable and produce same therapeutic outcome (ensure generics and brand name drugs are switchable)

Question 10

What is the role of the pharmacist in product selection?

Answer 10

• knowledge about BA and BE ensure confidence in addressing patient concerns regarding brand name vs generic, advising doctors, and reducing costs of drug therapy

Question 11

What was the ruling on July 23, 2011 made by the Supreme Court regarding?

Answer 11

makers of generic drugs can not be sued for failing to warn consumers of the possible SE of products if they copt the exact warnings from the brand name equivalents

Question 12

Absolute Bioavailability

Answer 12

extent or fraction of drug absorbed upon extravascular admin vs IV

Question 13

Relative Bioavailability

Answer 13

extent of drug absorbed upon extravascular admin vs dose size of standard by same route (ie: generic and brand name)

Question 14

Bioavailability

Answer 14

the relative amount of drug which enters systemic circulation and the rate at which it appears in the blood stream

Question 15

Bioequivalence

Answer 15

comparative bioavailability assessment of 2 or more formulations containing the same active ingredient to be administered by the same route - extent and rate of absorption are the same

Question 16

Bioequivalence Requirement

Answer 16

requirement imposed by FDA or TPD as a condition of marketing that there must be in vivo and/or in vitro testing of drug product

Question 17

Drug Product

Answer 17

finished dosage form that contains active ingredient (usually) with inactive ingredients

Question 18

Pharmaceutical Equivalents

Answer 18

drug products that contain identical amounts of same active ingredient and meet the same compendial standard of identity, strength, quality, purity, potency, and uniformity, disintegration/dissolution time
- does not have to contain same inactive ingredients

Question 19

Pharmaceutical Alternative

Answer 19

drug products with identical therapeutic moiety, but not necessarily same amount of dose or dosage form

Question 20

Pharmaceutical Alternative

Answer 20

drug products with identical therapeutic moiety, but not necessarily same amount of dose or dosage form

Question 21

Pseudo-generics

Answer 21

exact versions of innovator product - same ingredients, same factory, but repackaged

Question 22

Bioequivalent Drug Products

Answer 22

Pharmaceutical equivalents with no difference in rate and extent of absorption at the same dose, under similar conditions

Question 23

Therapeutic Equivalents

Answer 23

drug products which are pharmaceutical equivalents and have the same clinical effect and safety profile

Question 24

FDA Bioavailability vs TPD Bioavailability

Answer 24

a) rate and extent to which the active ingredient is absorbed from drug product and becomes available at site of action
- highlights “systemic availability”

b) rate and extent of absorption of drug into systemic circulation
- highlights “is absorbed”

Question 25

FDA Bioequivalence vs TPD Bioequivalence

Answer 25

a) lack of difference in the rate and extent ti which the active ingredient becomes available at the site of action when administered at the same molar dose under similar conditions
b) test and reference products have same Galenic form, contain same dose of active ingredients, and profiles of drug and/or metabolites are similar