# Presentation: 000988

## Regulation of Generic Drugs

**Office of Generic Drugs**
**Craig Kiester**
**Regulatory Support Branch**

## Outline

- Mission
- Legislative History and Waxman-Hatch
- What is a Generic Drug?
- Patents/Exclusivity
- Orange Book

## OGD Mission

**OGD Mission**

*  **To ensure that safe and effective generic drugs are available to the American People.*

## Legislative History

**Legislative History**

- _1906 Pure Food and Drug Act_ - establishes regulation of Food and Drugs.
- _1938 Food, Drug and Cosmetic Act_ - introduced safety standards.
- _1962 Kefauver-Harris Amendments to the FDA&C Act_ - tightened safety standards and introduced requirement that drugs must be effective.
_*1984 Waxman-Hatch Act*_ - created an abbreviated mechanism for approval of generic copies of all drugs approved approved after 1962, by stating that preclinical and clinical tests did not have to be repeated for generics.

## Innovator Incentives (Patents)

- Prior to 1984, a patent would run for 17 years from issue date or 20 years from filing
- W/H set to restore some incentive for innovation because pre-market approval requirements have increased
- W/H may restore up to 5 years not to exceed 14 years from the product’s approval date

## Innovator Incentives(cont.)

- URAA (June 8, 1995) made all patents in force or filed as of this date have the longer term of  17 years from issuance or 20 years from filing
- All patents filed after June 8, 1995 have an expiration date of 20 years from filing

## Exclusivity Incentives

- NCE protection - 5 years
- New salt or ester - 3 years
- New use or dosage form - 3 years

## Generic Incentives

- All approved products eligible for generic competition
- Eliminated requirement for duplicative clinical trials
- Created a regulatory process for faster approval of                generic drugs

## Definition of a Generic Drug

**Definition of a Generic Drug**

*A drug product that is comparable to a brand/reference listed drug product in *
*dosage form, strength, route of administration, quality and performance characteristics, *
*and intended use.*

## NDA vs. ANDA Review Process

## What are the Generic Drug Requirements?

**What are the ****Generic Drug Requirements?**

-  Same active ingredient(s)
-  Same route of administration
-  Same dosage form
-  Same strength
-  Same conditions of use

## Labeling

- “Same” as brand name labeling
- “Sameness” eliminates confusion and unsupported claims by different manufacturers
- May differ in excipients, PK data and how supplied

## When can a Generic Drug be Marketed?

**When can a Generic Drug ****be Marketed?**

- After patent & exclusivity protection ends, or
- patent owner waives its rights, or
- patent challenge is won, and
- FDA requirements are met

## Patent Protection

- Applies to NDAs only
- Delays final approval of ANDAs
- Agency is concerned with drug substance,                drug product and method of use patents
- Published in Orange Book

## Patent Certifications

- Paragraph I - Patent not submitted to FDA
- Paragraph II - Patent already expired
- Paragraph III - Tentative approval
- Paragraph IV - Court involvement

## Exclusivity Provisions

- Market protection
- 3 or 5 year period
- NCE prohibits ANDA submission
- Mutually exclusive
- 180 day exclusivity for first ANDA applicant(s) filed with a p IV certification to a particular patent/drug product

## 180 Day Exclusivity

- Blocks approval of subsequent ANDAs
- Awarded to first applicant(s) to file PIV to a listed patent/drug product, on the same day
- Triggered by either first commercial marketing or a court decision.
- Shared Exclusivity (multiple patents or multiple filers)

## Tactics to delay Generic Competition	 

- Serial Patent Filings: multiple 30 month stays
- Agreements not to market: Generic and Innovator
- Agreements not to initiate litigation: Generic and Innovator
- Citizen’s Petitions: change in BE studies, not same drug product...
- Changes to Reference Listed Drug Product.

## Title XI of the Medicare Modernization Act

- Passed as law 12/8/2003
- Some provisions retroactive to August of 2003
- Only one 30 month stay per ANDA (some exceptions)
- Exclusivity based on drug product not by patent
- Provisions for Forfeiture of 180 day exclusivity

## APPROVED

- U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
- PUBLIC HEALTH SERVICE
- FOOD AND DRUG ADMINISTRATION
- CENTER FOR DRUG EVALUATION AND RESEARCH
- OFFICE OF MANAGEMENT
- DIVISION OF DATABASE MANAGEMENT

**APPROVED**
**DRUG PRODUCTS**

**WITH**
**THERAPEUTIC EQUIVALENCE EVALUATIONS**
**20****TH**** EDITION**

- THE PRODUCTS IN THIS LIST HAVE BEEN APPROVED UNDER
- SECTION 505 OF THE FEDERAL FOOD, DRUG, AND
- COSMETIC ACT.

**2000**

## “Orange Book”

**“****Orange Book”**

-  Therapeutic equivalence codes
- “A” = Substitutable
- “B” = Inequivalent, NOT substitutable

-  Expiration dates:  patent and exclusivity

-  Reference Listed Drugs/brand drugs identified by
-    FDA for generic companies to compare their
-    proposed products with