Chemistry Reference
In-Depth Information
associated with the drug.
Phase 3
includes expanded controlled and uncontrolled trials
once enough evidence suggesting effectiveness of the drug has been obtained. The
studies in this phase are intended to gather additional information about effectiveness and
safety that is needed to evaluate the overall bene
risk relationship of the drug. The
studies in this phase, performed on several hundred to several thousand patients, also
provide adequate basis for the information in the physician labeling.
New Drug Application
(NDA) is the vehicle through which the sponsor formally
proposes that the FDA approves the sale of a new drug in the United States.
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It includes
test data and analysis from the clinical
t
-
trials in human subjects, along with full
information on manufacturing speci
cations, stability and bioavailability data, method
of analysis of each of the dosage forms the sponsor intends to market, packaging and
labeling for both physician and consumer, and the results of any additional toxicological
studies not already submitted in the IND application. The 1992 Prescription Drug User
Fee Act (PDUFA) established a two-tiered system for the drug approval process.
Standard Review
is applied to a drug that offers, at most, only minor improvement
over existing marketed therapies. The goal for completing a Standard Review is
10 months. Most NDAs undergo a Standard Review.
Priority Review
designation is
given to drugs that offer major advances in treatment, or provide a treatment where none
existed. The goal for completing a Priority Review is 6 months.
The results of the clinical trials comprise the single most important factor in the
approval or disapproval of a new drug. In addition to the clinical and nonclinical data and
analyses, an NDA must also provide suf
cient information on chemistry, pharmacology,
medical, biopharmaceutics, statistics, manufacturing and control of the drug to allow
FDA to determine safety and effectiveness of the drug for the proposed use, risk
t
of the drug, proposed labeling, and whether the manufacturing methods and controls are
adequate to preserve the identity, strength, quality, and purity of the drug.
The FD&C Act that was enacted in 1938 only required NDAs to contain information
pertaining to the safety of the new drug. The Kefauver
-
bene
Harris Amendments to the FD&C
Act, 1962, added the requirement of the NDAs to contain evidence of the effectiveness of
the new drug for its intended use and that the established bene
-
its of the drug outweighed
its known risks. The requirements of the NDA were again modi
ed in 1985, mainly to
restructure the ways in which information and data are organized, thereby expediting the
FDA review process. Although the exact requirements are a function of the nature of a
speci
c drug, the NDA must provide all relevant data and information that a sponsor has
collected during the product
s research and development.
A review of an NDA involves FDA reviewers, from multiple scienti
'
c aspects,
including, chemistry, pharmacology/toxicology, medical, biopharmaceutics, and statis-
tics, recon
cacy
of the drug. If needed, additional or reanalysis of the submitted data is performed.
The review team looks for possible issues with the application, such as weaknesses of
the study design or analyses. Reviewers determine whether they agree with the
sponsor
rming and revalidating the sponsor
'
s conclusions on the safety and ef
is results and conclusions, or whether additional information is needed to
make a decision. Each reviewer prepares a written evaluation containing conclusions
'
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Title 21, Code of Federal Regulations, Part 314. New Drug Application, 2012 ed.
