APPROVED PRESCRIPTION DRUG PRODUCTS - FDA Law Blog

252 Pages·2009·9.27 MB·English

APPROVED PRESCRIPTION DRUG PRODUCTS
with
THERAPEUTIC EQUIV ALENCE EVALUATIONS
The products in this list have been approved under sec
tions 505 and 507 of the Federal Food, Drug, and Cosmetic
Act. This volume and accompanying first supplement are
current through August 31, 1980.
u.s.
Department of Health and Human Services
Public Health Service
Food and Drug Administration
Bureau of Drugs
1980

RXD AND DRUG ACMINISTRATION
APProVED PRESCRIPTION DRUG ProDUCTS
- with Therapeutic Equivalence Evaluations -
Table of Contents
I. Preface
A. Introduction
B. Definitions
c. General Policies Governing the List
D. Legal status of the List
E. Precautions to Users of the List
F. Codes and Specific Policies for Therapeutic Equivalence Evaluations
G. Description of Special Situations
H. Updating Procedures
II. Listings
A. Format Guide
B. Drug Product List
C. Trade Name Index
D. Application Holder Index
E. Application Holder Abbreviation List
F. Appendix: Prescription Drug Products Deemed Approved -
Pending Resolution of Safety or Effectiveness Issues
Addi tional copies of the List and supplements may be obtained by subscrip
tion from:
United States Goverment printing Office
Washington, D. C. 20402
(Refer to the p.lblication by name)
For sale by. the Superintendent of Documents, U.S. Government Printing Office
Washington, D.C. 20402

FOOD AND DRUG ADMINI STRATION
APPROVED PRFS::RIPTION DRtX; PRODUCTS
- With Therapeutic Equivalence Evaluations -
I. PREFACE
A. INTRODUCTION
The Approved Prescription Drug Products list (the List) provides a list
of currently marketed prescription drug products that have been approved for
marketing on the basis of safety and effectiveness by the Food and Drug
Administration (FDA). In addition, it contains therapeutic equivalence
evaluations for multiple source drug products. These evaluations have been
prepared to pvomote public education in the area of drug product selection,
to foster containment of health costs, and to serve state health agencies in
the administration of their drug product selection laws.
For several years there has been a trend toward repeal of anti
substitution legislation that once was common in most States. In addition,
most States have adopted laws intended to encourage or mandate the substitu
tion of one product of a particular drug entity for another, with the intent
of saving money for the consumer and containing costs in drug procurement
and medical reimbursement programs. These State laws generally require that
either substitution be limited to drugs on a specific list (the positive
formulary approach) or that substitution be permitted for all drugs except
those prohibited by a particular list (the negative formulary approach). .
A number of States have sought the assistance of FDA in preparing both
posi tiv e and negativ e formular ies. For example, on January 23, 1978 FDA
responded to a request fDOm the New York State Health Department to evaluate
their list of drug products for therapeutic equivalence. Subsequently, a
similar evaluation was made of a list suJ:mi tted by the State of Illinois.
The basic policies awlied in evaluating these lists for the States of New
York and Illioois are identical to the policies applied in developing this
List.
Because of the number of requests for assistance in developing drug
lists fran other States, it became awarent that FDA could not serve the
needs of each State on an individual basis. The agency also recognized that
a single list based on common policies would be preferable to attempting to
evaluate drug products on the basis of differing definitions and criteria in
various State laws. As a result, on May 31, 1978, the Camnissioner of Food
and Drugs sent a letter to officials of all States informing them of FDA's
intentim to prepare a list of all prescriptim drLB products that are
approved by FDA for safety and effectiveness, and, in the case of multi
source products, those products containing the same active ingredients and
are identical in strength, dosage form, and route of administration that the
agency evaluates f~ therapeutic equivalence.
The Approved Prescription DrLB Prodocts list, which was distributed as
a proposal in January 1979, includes currently marketed prescripticn drug
prodocts approved by FDA through new drug applicaticns (NDA's) or abbrevi
ated new drug applicatims (ANnA's) under the provisicns of section 505 of
the Federal Food, Drug, and COS1letic Act (the act), or in the case of
antibiotics, through analogous applicaticns known as Forms 5 or 6 under
secticn 507 of the act. In preparing the List, FDA initially drew fran its
computerized files of approved drLB sul::missicns. In order to minimize the
potential for error, an autanated list of approved NDA's, ANnA's, and
ant ibiot ic Forms 5, as of Apr il 1978, was published as an inter im document
in May 1978 and sent to state officials and agencies, including health
officers, boards of pharmacy, and drLB procurement agents, for review and
cooment. By notice published in the Federal Register of June 30, 1978
(43 FR 28557), the interim List was also made available to the public, with
a request for additims, deletims, or correcticns. In addition, on two
separate occasims, FDA sent to each applicaticn holder data \\Qrksheets
listing its prodocts that FDA had identified as being approved and corree
tims were solicited. The agency received an excellent response with
ccnsiderable updating inf~maticn, indicating a serious and careful review
by the firms. Informaticn received in response to these requests was
reviewed and when applicable was incorporated into the autanated file.
Informatim regarding approved antibiotic Forms 6 (the antibiotic applica
tim analogous to the ANDA) also was included. The List, together with its
first supplement, contains approved NDA' s, ANDA' s, Forms 5, and Forms 6
through the last month prior to publication. Those prescription drug
products for which approval has been withdrawn for whatever reason are
excluded fran the List.
The therapeutic equivalence evaluaticns in the List reflect FDA's
applicatim of specific criteria to the approved multisource drug products
on the List. The evaluatims are presented in the form of code letters that
indicate the basis for the evaluaticn made. An explanaticn of the code
atpears later in this preface. The List, including the therapeutic equiva
lence evaluaticns, was distributed in January 1979 as a proposal so that
interested parties could review and comment m it. This publicaticn
reflects correcticns and additicns made as a result of those cornnents
received.
In addi tim to the list of approved drug products and therapeutic
equivalence evaluatioos, this publicatioo also includes: an index of drug
products by trade or brand name, an index by name of the holder of the
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approved application, a list of application holders including an abbreviated
name designation, and an appendix of drug products still being evaluated for
effectiveness in the Drug Efficacy study Implementation (DESI) program.
A complete discussion of the background and basis of FDA's therapeutic
equivalence evaluation policy was p..1blished as a proposal in the Federal
Register on January 12, 1979 (44 FR 2932) . The final rule, which includes
FDA's responses to the p..1blic comnents rece i ved on the proposal, was
recently published in the Federal Register.
B. DEFINITIONS
Approved Prescription Drug Products - This term refers to currently
marketed prescription drug products approved by FDA through new drug
applications (NDA's) or abbreviated new drug applications (ANDA' s) under the
provisions of section 505 of the Federal Food, Drug, and Cognetic Act (the
act) or, in the case of antibiotics, through analogous applications known as
Forms 5 or Forms 6 under section 507 of the act. All drug products on the
List have been fully reviewed and awroved for safety and effectiveness by
FDA. The law also permits drugs to be legally marketed without such fully
approved applications under certain circumstances, but the drugs so marketed
do not appear on the List. They consist primarily of: 1) drugs marketed
prior to 1938 that are rot subject to the pre-market clearance procedures of
the law, and 2) drug products marketed between 1938 and 1962 that were
approved for safety but rot effectiveness ("deemed awroved") and are still
being reviewed under the administrative procedures of the Drug Efficacy
Study Implementaticn (DESI) program. The drug products still in the DESI
administrative process are listed in an awendix to the List.
Pharmaceutical Equivalents Drug products are considered to be
pharmaceutical equivalents if they contain the same active ingredients and
are identical in strength, dosage form, and route of administration (e.g.,
chlordiazepoxide HCl, 5 mg. capsules, made by tVXl or more different manu
facturers) . pharmaceutically equivalent drug products, sometimes called
chemical equivalents, are formulated to contain the same amount of active
ingredient in the same dosage form and to meet the same or comparable
standards (i.e. identity, strength, p..1rity and quality), but they may differ
in characteristics such as color, taste, shape, packaging, expiration time,
and, within ce,ttain limits, labeling.
Pharmaceutical Alternatives - Drug products are considered to be
pharmaceutical alternatives if they contain the same therapeutic moiety but
differ in the salt or ester of that moiety or in the dosage form or strength
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(e.g., tetracycline hydrochlor ide, 250 mg. capsules vs. tetracycline
phosphate complex, 250 mg. capsules~ diazepam, 2 mg. tablets vs. diazepam,
10 mg. tablets). Different dosage forms and strengths within a product line
qy a single manufacturer are thus pharmaceutical alternatives, as are
controlled release products when compared with conventicnal formulations of
the same active ingredient.
Therapeutic Ek;rUivalents - Drug products considered to be therapeutic
equivalents are pharmaceutical equivalents and can be expected to have the
same therapeutic effect when crlministered to :patients under the conditicns
specified in the labeling. The cona:pt of therapeutic equivalence, as used
in developing the List,awlies cnly to products containing the same active
ingredients and does not encompass a comparison of pharmaceutical .;literna
tives or two different active ingredients used for the same disease (e.g.,
propoxyphene HCl am pentazocine for the treabnent of :pain). FDA evaluates
as therapeutically equivalent those drug products that meet the follCMing
general criteria: (1) They are pharmaceutical equivalents in that they
(a) cootain identical amounts of the same active drug ingredient in the same
dosage form, and (b) meet compendial or other awlicable standards of
identity, strength, quality, and purity~ (2) They are bioequivalent in that
(a) They do not present a knCMn or potential bioinequivalena: problem, or
(b) If they cb present such a known or potential problem, they are shown to
meet an appropriate bioequivalence standard; (3) They are adequately
labeled~ (4) They are. manufactured in compliance with Current Good Manu
facturing Practia: regulations.
FDA coosiders drug products to be therapeutically equivalent if they
meet the cr i ter ia outlined al:ove, even though they may differ in certain
other characteristics, e.g., color, flavor, :packaging, expiration time, and
minor aspects of labeling. When such differences are important in the care
of a particular :patient, it is awropriate for the prescribing physician to
require that a particular brand be dispensed as a medical necessity. As
loog as this coosideraticn is met, however, FDA believes that products
coosidered therapeutically equivalent can be substituted with the full
expectaticn that the substituted product will produce the· same therapeutic
effect as the prescr ibed prodoct.
C. GENERAL roLICIES OOVERNIN3 THE LIST
The fundamental policy governing the List is that FDA considers
pharmaceutically equivalent drug products to be therapeutically equivalent
provided they are approved for both safety and effectiveness, are manufac
tured in accordance with Current Good Manufacturing Practice regulatioos,
meet the same or equivalent standards, and, in those instances where
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