Chemistry Reference
In-Depth Information
and recommendations about the application. The technical review and recommendations
from different review teams are combined in an action letter recommending approval,
approvable, or nonapprovable decision on the application and a justi
cation for that
recommendation. If an application is not approved, FDA issues a Complete Response
Letter to the sponsor listing all de
ciencies in the application that the sponsor must
address in order for the application to be reconsidered for approval. The de
ciencies may
be major (e.g., unexpected safety issues or failure to demonstrate effectiveness of the
drug that may require additional clinical trials) or minor (e.g., labeling changes).
The
final approval of an NDA, in some cases, is also dependent on a preapproval
inspection of the sponsor
s manufacturing facilities and clinical trial sites in which the
FDA investigators audit and verifies manufacturing-related statements and commitments
made in the NDA against the sponsor
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s manufacturing practices. Preapproval inspections
are generally conducted for product (i) that is a new chemical or molecular entity, (ii) that
has a narrow therapeutic range, (iii) that represents
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first approval for the applicant, or
(iv) that is sponsored by a company with a history of CGMP problems or that has not
been the subject of a CGMP inspection over a considerable period. Approval can be
delayed if the facility is not ready for inspection. In addition, manufacturing de
ciencies
found during inspection must be corrected before an approval is granted by the FDA.
Upon approval, all new drugs are available by prescription only.
Some new drugs, especially those for serious and life-threatening diseases that lack
satisfactory treatments, may be granted an
accelerated approval
by the FDA before
measures of effectiveness are available. For these drugs, FDA relies on less traditional
measures called surrogate endpoints to evaluate effectiveness. These are laboratory
findings or signs that may not be a direct measurement of how a patient feels, functions,
or survives, but are considered likely to predict bene
rm
the initial results, FDA may withdraw an approval granted under the accelerated
approval rules.
Most new drugs, like other new products, are frequently under patent protection
giving their sponsors sole right to sell these drugs while the patent is in effect. When the
patents or other periods of exclusivity expire, other drug product manufacturers may
apply to the FDA to obtain market authorization to sell generic versions of these drug
products in the United States. A generic drug product is one that contains the same active
ingredient(s) as the innovator drug product, although the inactive ingredients may vary. It
must also be identical in dosage form, strength, and route of administration and have the
same use indications. They are required to meet the same requirements for identity,
strength, purity, and quality, and be manufactured under the same strict standards of
FDA
t. If studies do not con
s good manufacturing practice regulations required for the innovator drug prod-
ucts. The Waxman
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Hatch Act of 1984 requires the generic drugs to be bioequivalent to
the innovator drug, that is, they must deliver the same amount of active ingredients into a
patient
-
s bloodstream in the same amount of time as the innovator drug. For approval,
generic drugs sponsors need to provide scienti
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c evidence that the generic drug is
interchangeable with or therapeutically equivalent to the originally approved drug. All
approved products, both innovator and generic, are listed in FDA
s publication titled
Approved Drug Products with Therapeutic Equivalence Evaluations
, commonly known
as the Orange topic. The publication also identi
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es the Reference Listed Drug (RLD)
