Presented By: Juned Siddique Md Waseem Sumit Chauhan

Approved Drug Products with Official Title Therapeutic Equivalence Evaluation

Orange Book

Called because of the documents Orange colored Cover Page

FDAs list of all drugs approved in USA as safe & effective Authoritative Source of Information on the Therapeutic Equivalence of Drug Products

1950s

Many states enacted laws banning substitution of drugs Economic pressure led to repeal of these anti substitution laws

1970s

In order to regulate substitution, FDA announced its intention to create list of approved drugs & Therapeutic Equivalence determination

1st Edition

October 1980

5 Main Sections:

Introduction
Drug Product List

Appendices
Patent Exclusivity Info Addendum

Drug products which contain the same Pharmaceutical active ingredients in the same strength Equivalents and dosage form delivered by the same route of administration

Bioequivalent Drug Products

Those products which have shown comparable bioavailability when studied under similar conditions (e.g. the rate and extent of absorption of a test drug does not significantly differ from that of the reference drug)

Therapeutic Equivalents

Pharmaceutical Equivalents that are Bioequivalent. Only drugs which are Therapeutic Equivalents may be legally substituted for FDA approved drugs in Orange Book.

FDA Considers therapeutically equivalent & therefore substitutable

T.E. CODES

FDA Considers NOT to be therapeutically equivalent due to actual or BE problems

A DRUGS
AA (no known or suspected BE problems)
AB (actual or potential BE problems have been resolved

B DRUGS

Reference Listed Drug Condition of Approval

The listed drug identified by FDA as the drug product upon which applicant relies in seeking approval of its ANDA Bioequivalence to the innovator drug product must be proven. Once proven, the generic drug is listed in the ORANGE BOOK

Designating a Single Reference Listed Drug as Standard FDA hopes to avoid possible Generic variations

Multi Source

Pharmaceutical Equivalents available from more than one manufacturer. Therapeutic Equivalence code is included (Section 505)

Only one approved product available Single Source for that active ingredient, dosage form, route of administration & strength. No Therapeutic Code included.

FDA Considers therapeutically equivalent & therefore substitutable Multisource drug products listed under the same heading and having same strength generally will be coded AB In certain instances, a number is added to the end of AB code to make it 3 character code (AB1, AB2, etc) Assigned only in situations when more than one reference listed drug of the same strength has been designated under same heading

Labeling Difference Different amount of Drug Package Size

Pharmaceutical Equivalents Powders for reconstitution.

Strength should not vary by more than 1%

Difference not considered as Pharmaceutically equivalent

FDA Considers NOT to be therapeutically equivalent & therefore substitutable

BC BD BE BS BT

BX

BN BP

BR

Amino Acid & These products differ in amount and Protein kinds of amino acids they contain. Hydrolysate Considered TE where nitrogen balance is sole objective injections Waived Exclusivity
For an NDA qualifies for exclusivity, the FDA will delay approval of application ANDA until the expiration of exclusivity

Before making changes FDA announces Introduction & invites Comments Comments along with BE data sent to Director, Division of BE Comment period will generally be 60 days

Arranged Alphabetically by Active Ingredient

Contains Product Identification Information

Contains application number, drug product number and approval dates N NDA & A - ANDA

Active ingredient headings for multi ingredient products arranged alphabetically

Identifies drug that qualify under the Drug Price Competition and Patent Restoration Act for period of exclusivity
It Prevents submission or effective approval of ANDAs