PHSC1424 Biopharm - Unit 6 Lecture 2 Bioavailability and Bioequivalence Studies (MAY ADD MORE)

Pharmaceutical alternatives

two drugs with the same active ingredient that may differ in salt, dosage form, or strength

Different dosage forms or strengths

example of pharmaceutical alternatives

Active ingredient

What is the same for pharmaceutical alternatives?

Salt, dosage form, strength

What might differ for pharmaceutical alternatives?

Pharmaceutical equivalents

two drugs with the same active ingredient, salt, dosage form, and strength; same USP standards (strength, quality, purity, identity), and may differ in shape, color, excipients, release mechanism, packaging, labeling, and expiration date

Same drug products and form from different manufacturers

example of pharmaceutical equivalents

Active ingredient, salt, dosage form, strength, USP standards

What is the same for pharmaceutical equivalents?

Shape, color, excipients, release mechanism, packaging, labeling, expiration date

What might differ for pharmaceutical equivalents?

Therapeutic equivalents

two drugs that are considered to have the same clinical effect and safety profile; defined by the Drug Price Competition and Patent Term Restoration Act of 1984

Clinical effect and safety profile

What is the same for therapeutic drug equivalents?

Generic manufacturers can gain FDA approval via ANDA

What did the Drug Price Competition and Patent Term Restoration Act of 1984 allow?

New pre-clinical data or proof of safety/efficacy

What do ANDAs not include?

Good manufacturing practices and bioequivalence

What do ANDAs have to ensure?

Hatch-Waxman Act

created a regulatory framework that allows generic versions of brand-name drugs to enter the market after the brand-name drugs' patents expire

Bioavailability (F)

defined in 21 CFR 320.1 as 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

Rate and extent to which active ingredient or moiety is absorbed

How does the FDA/DEA define bioavailability?

Bioequivalence

defined in 21 CFR 320.1 as 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 becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study

Absence of significant difference in rate and extent to which active ingredient or moiety in pharmaceutical equivalents or alternatives is available at site of action

How does the FDA/DEA define bioequivalence?

Bioequivalence studies

typically used for generic drug substitution for brand name products, clinical trial formulations and marketed drug product, early and late clinical trial formulations, drug stability formulations versus clinical trial formulations, and significant alterations in drug formulation

FDA-approved drug products, discontinued drug products, and drug patents and period of market exclusivity

3 things the FDA orange book lists

FDA Orange Book

provides ratings for therapeutic equivalence between medications via a coding system indicating bioequivalence of the generic drug to the reference listed drug (RLD) used to gain FDA approval

A or B, 2

Codes in the FDA Orange book start with what letters and must contain at least how many letters?

A-rated

drugs that have been determined to be bioequivalent to the brand drug

B-rated

drugs that are considered not to be bioequivalent to the brand drug

AA

A-code rating meaning conventional dosage form with no bioequivalence problems

AB

A-code rating meaning the product meets the necessary bioequivalence requirements

Therapeutically equivalent, displaying bioequivalence and pharmaceutical equivalence

A generic medication with an AB rating has in vivo or in vitro study results proving that it is what?

Reference Listed Drug (RLD)

brand-name drug that went through FDA approval via the NDA process

Aqueous solutions, they require no dissolution

products where bioequivalence studies are typically not necessary, and why

Oral drugs

products where bioequivalence studies are required

Yes, but it can vary by state

Can pharmacists substitute less expensive generics for brand-name drugs?

Yes, but it can vary by state

Can pharmacists substitute less expensive generics for brand-name drugs?

12-15 years

How long does the NDA process take?

1-1.5 years

How long does the ANDA process take?

NDA

process that new drugs have to undergo

Preclinical and IND submission, clinical trials, NDA submission, FDA review and decision

4 parts to NDA process

ANDA

process that generic drugs have to undergo

Identify reference listed drug (RLD), bioequivalence and CMC studies, ANDA submission, FDA review and decision

4 parts to ANDA process

Generic

Are brand or generic drugs utilized more?

Brand

Do brand or generic drugs make up more total spending?

Crossover design

bioequivalence study design where every subject gets both treatments and serves as his/her own control, and a washout period separates the treatments

Washout period

must separate treatments in a crossover design; at least 5 PK half-lives

At least 5 half-lives

How long should a washout period in a crossover design be?

24-36

How many health volunteers should be utilized in a crossover bioequivalence study?

12-18 spanning at least 3-4 half-lives

How many blood samples, including predose, should be taken for each subject?

3-4

minimum blood samples taken during terminal elimination phase to accurately estimate elimination rate constant and half-life