Federal Law - Bringing New Drugs to Market

New Drug" definition

A drug that is not generally recognized by experts
as safe and effective for use under the conditions recommended in the
drug's labeling.

New Drug" examples

New molecular entity
Drug already approved by FDA w/ new: AI, therapeutic indication,
formulation/manufacturer, dosing schedule/route of admin, combination
of products.

1. Pre-clinical studies

FDA approval not required prior
Assesses therapeutic effects and safety on animal subjects
Investigators/sponsors req'd to follow GLP

2. Investigational New Drug (IND) Application

1st application form to be submitted prior to administering "new
drug" to humans

It is illegal to distribute a drug unless it has an approved
_______ on file.

IND contents

Drug name
Composition
Methods of manufacturing and QC
Pharmacologic and pharmacokinetic data

How long does FDA have to decide if IND is suitable for testing?

30 days

3. Clinical Trials

Has 3 phases
FDA can terminate at any point if deemed necessary
Pt/representative must provide informed consent in each phase

Phase 1 Clinical Trials

Subjects: < 100 healthy individuals

Phase 1 Clinical Trials

Purpose is to evaluate drug safety, toxicity, absorption, metabolism,
and elimination

Phase 2 Clinical Trials

Hundreds of subjects affected by disease or symptoms of condition

Phase 2 Clinical Trials

Purpose is to determine effectiveness of drug and doses at which
efficacy occurs

Phase 3 Clinical Trials

Hundreds to thousands of subjects

Phase 3 Clinical Trials

Purpose is to collect all necessary data to meet safety and efficacy
standards for FDA approval.

Treatment IND

Allows for administration of IND to pts not enrolled in clinical
trial. Must be imminent, life-threatening w/ no current cure or where
current drugs are not effective.
Must have safety and efficacy data AND be in phase II or III of
clinical trial.
Must submit treatment protocol to FDA

4. New Drug Application (NDA)

Must include:
Reports of investigations showing drug safety and efficacy
Drug components & composition
Methods of manufacturing, processing, & packaging
Samples of drug and components
Any proposed labeling

Minimum length of time FDA reviews NDA

6 months

If approved, the NDA is ___________ and the drug may be ___________
by the manufacturer.

on file"; marketed

5. Post-marketing Surveillance

Subjects are all patients receiving drug

5. Post-marketing surveillance

Purpose is to report adverse effects on widespread population.

5. Post-marketing Surveillance

Concerned w/ long term safety profile in larger pt population
Manufacturer must maintain and est. post-marketing records &
provide annual reports.
FDA determines if drug stays on market

FDA MedWatch Program

System which HCPs can report any problems with use of drugs. Part of
Post-marketing Surveillance.

Type P

Priority" therapeutic classification
Major therapeutic gain
No other effective drugs available/has significant advantages
compared to current drugs

Type S

Standard/similar" therapeutic classification
Similar to other drugs on the market

Type O

Orphan drug" therapeutic classification

Chemical Classification

Types 1 - 6

Fast Tract Products

Accelerated review request if drug:
Intended to treat serious/life-threatening condition
Will fulfill unmet medical need Likely to provide
clinical benefit

Act that granted Fast Track Products

FDA Modernization Act of 1997

Abbreviated New Drug Application (ANDA)

May be submitted when "innovator" drug patent expires.
First applicant to complete demonstrating equivalent generic is
awarded 6 months exclusivity on sale of generic

ANDA requires _______ data than IND/NDA, but must prove
_______________ _______________.

less, Pharmaceutical equivalence

The Approval Process

Pre-clinical studies IND application Clinical
trials NDA Post-marketing surveillance

Supplemental New Drug Application (SNDA)

New use for existing drugs
Used when manufacturer wants to change drug's:
Synthesis production procedure manufacturing
location packaging labeling dosage
form/strength therapeutic indication

Orphan Drugs

Used for treatment of "rare diseases" affecting small pt population

Rare disease

Affects <200,000 persons in US

Orphan Drug Act of 1983

Offered tax relief, exclusive marketing rights, and faster NDA
approval to encourage development of orphan drugs.