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Dr Sumanta Mondal
GITAM (Deemed to be University)
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PREPARATION AND EVALUATION OF NANODOSAGE FORMS OF SELECTED NON-STEROIDAL ANTI-INFLAMMATORY DRUGS AND ITS MANAGEMENT IN ORAL AND
COLORECTAL CANCERS View project
All content following this page was uploaded by Dr Sumanta Mondal on 10 May 2018.
Objectives
To allow review of patterns of access and usage
To allow discovery of use of unusual privileges
To allow discovery of repeated attempts to bypass protections
To serve as a deterrent by its existence
To supply an additional form of user assurance
Lecture Notes_Dr. Sumanta Mondal_M.Pharm 1th Sem. _ GITAM Institute of Pharmacy. Page | 1
THE ORANGE BOOK
1. INTRODUCTION
1.1 Content and Exclusion
1.2 Therapeutic Equivalence-Related Terms
1.3 Statistical Criteria for Bioequivalence
1.4 Reference Listed Drug
1.5 General Policies and Legal Status
1.6 Practitioner/User Responsibilities
1.7 Therapeutic Equivalence Evaluations Codes
1.8 Description of Special Situations
1.9 Therapeutic Equivalence Code Change for a Drug
Entity
1.10 Change of the Therapeutic Equivalence Evaluation for
a Single Product
1.11 Discontinued Section
1.12 Changes to the Orange Book
1.13 Availability of the Edition
2. HOW TO USE THE DRUG PRODUCTS LISTS
2.1 Key Sections for Using the Drug Product Lists
2.2 Drug Product Illustration
2.3 Therapeutic Equivalence Evaluations Illustration
DRUG PRODUCT LISTS
Prescription Drug Product List
OTC Drug Product List
Drug Products with Approval under Section 505 of the
Act Administered by the Center for Biologics
Evaluation and Research List
Discontinued Drug Product List
Orphan Products Designations and Approvals List
Drug Products Which Must Demonstrate in vivo
Bioavailability Only if Product Fails to Achieve
Adequate Dissolution
APPENDICES
A. Product Name Index A-1
B. Product Name Index Listed by
C. Uniform Terms
PATENT AND EXCLUSIVITY INFORMATION ADDENDUM
A. Patent and Exclusivity Lists
B. Patent and Exclusivity Terms
Lecture Notes_Dr. Sumanta Mondal_M.Pharm 1th Sem. _ GITAM Institute of Pharmacy. Page | 2
THE ORANGE BOOK
1. INTRODUCTION
1.1 Content and Exclusion
Approved OTC drug products for those which are not marketed
Approved prescription drug with therapeutic equivalence evaluations
Drug products with Biologics Evaluation and Research
List of approved products that have been discontinued from marketing
1.2 Therapeutic Equivalence-Related Terms
Pharmaceutical equivalents
Contain the same active ingredient(s),
Have the same dosage form and route of administration, and
Identical in strength or concentration
May differ in shape, release mechanisms, and packaging
Pharmaceutical alternatives
Contain the same therapeutic moiety but might differ in ,
Salts, esters, or complexes form of the same moiety,
Different dosage forms,
Different strengths
Therapeutic equivalents
Therapeutic equivalents are expected to have the same clinical effect and safety profile.
Drug products are considered therapeutic equivalents if they are all of the following
Pharmaceutical equivalents
Bioequivalent
Approved as safe and effective
Adequately labeled
Manufactured in compliance with current Good Manufacturing Practice regulations
Bioequivalence and Bioavailability
Drug products are considered bioequivalent if they are pharmaceutical equivalents whose rate and
extent of absorption are not statistically different when administered to subjects at the same molar dose
under similar experimental conditions
Bioequivalence use to determine Therapeutic Equivalents
1.3 Statistical Criteria for Bioequivalence
In short Bioequivalence refers to equivalent release of the same drug substance from two or more drug
products.
The standard bioequivalence (PK) study is conducted in 24-36 adults using a two-treatment crossover
study design.
Alternately, a four-period, replicate design crossover study can also be used.
The statistical methodology for analyzing these bioequivalence studies is called the two one-sided test
procedure.
Two situations are tested with this statistical methodology
Pharmacokinetic parameters determine are AUC and Cmax.
Two criteria includes,
i. Whether a generic product (test), when substituted for a brand-name product (reference) is
significantly less bioavailable. (A limit of test-product average/reference-product average of 80%)
ii. Whether a brand-name product when substituted for a generic product is significantly less
bioavailable. (A limit of reference-product average/test-product average 125%)
A difference of greater than 20% for each of the above tests was determined to be significant
The confidence interval for both pharmacokinetic parameters, AUC and Cmax, must be entirely within
the 80% to 125% boundaries cited above.
Lecture Notes_Dr. Sumanta Mondal_M.Pharm 1th Sem. _ GITAM Institute of Pharmacy. Page | 3
THE ORANGE BOOK
Lecture Notes_Dr. Sumanta Mondal_M.Pharm 1th Sem. _ GITAM Institute of Pharmacy. Page | 4
THE ORANGE BOOK
Lecture Notes_Dr. Sumanta Mondal_M.Pharm 1th Sem. _ GITAM Institute of Pharmacy. Page | 5