Principles and Practice of Pharmaceutical Medicine

Information Act, which provides free access to the
Summary Basis of Approval document for all
approved drugs in the United States, facilitates
this exercise.
If one has a close, but not identical, copy of
a drug, then the second way to an ANDA is to file a
petition under 21CFR para 314.93(b), identifying
what the differences may be from the approved
product, and making a case why the new drug
should be the subject of a forthcoming ANDA.
Successful examples have included differences
in excipients, minor differences inex vivodisso-
lution studies, and other matters which can be
argued not to have much clinical impact. FDA
will rule on this petition, and there are various
appeals procedures if the ruling is unfavorable.
The checklist of matters to cover in the petition
is as follows:

Identity of active ingredients.

Expectation of the same therapeutic effect.

Failure of the new product to meet the definition
of a ‘New Drug’ under 21CFR para 314.1 and
Section 201(b) of the Federal Food, Drug and
Cosmetic Act (21USC, 301–392).

It should be noted that the therapeutic equiva-
lence expectation is precisely that no comparative
clinical studies are required. A phase I pharma-
cokinetic study, in support of the therapeutic
equivalence, may be helpful but need not
contribute any pharmacodynamic data. With a
favorable ruling on this petition, the ANDA
may then follow.
The overall structure of the ANDA is described
in 21CFR para 314.94. Its component parts are as
follows:

Application Form

Table of contents

Basis of the ANDA, covering either the question
of identity, or the results of a petition, as
described above

Description of the conditions of use, and show-

ing its similarity to the previously approved drug

(usually best done simply by plagiarizing large

sections of the previous package insert)

Description of the active ingredients

Route of administration, dosage and strength

Bioequivalence data

Previous drug’s label and proposed labeling

Chemistry, manufacture and controls

Samples for testing in FDA’s own laboratories

Other information

Patent certification

In practice, in comparison to an NDA, the chem-

istry, manufacturing and controls section of an

ANDA is just as long, but all the other sections

are much abbreviated from an ordinary NDA. The

issue of patents is covered elsewhere, but template

wording for the certificates is provided, according

to the various types of patent, in 21CFR paras

314.94–314.95.

Post-marketing requirementsfor an ANDA are

similar to those for an orthodox NDA, and not as

stringent as for an accelerated approval for a ser-

ious or life-threatening disease (see above). The

usual processes are available for amending

ANDAs, either before or after approval.

The ANDA process has permitted large numbers

of generic drugs to be provided to the general

public at lower cost. The process was created at

the same time as the orphan drug procedures, and

the Waxman–Hatch Act in the United States Con-

gress. Many view the ANDA and the orphan drug

initiatives asquid pro quo, and certainly both

were the subject of negotiation with the US

pharmaceutical industry.

Final comments. The intent of this chapter

has been to provide the context and philosophy

behind these special procedures. All these special

IND and NDA procedures are now widely used

32.5 ACCELERATED APPROVALS: ANDAS AND GENERIC DRUGS 413