NDA Approval
Process
Presented By : Pooja Ghatole GUIDED BY :-
M Pharm(Sem-1 ) Dr. D. L. Visokar
Subject –Regulatory Affairs (Dept.Of Assistant professor
Pharmaceutics) Department
Roll No – PH105 of pharmaceutics
Modern College Of Pharmacy Nigdi
Definitions
Drug :
Drug are the substance intended to be used for or in the diagnosis,
treatment, mitigation, or prevention of any disease or disorder in human being
or animal.
New Drug :
Drug that has not been declared safe and effective by qualified expert
under the condition prescribed, recommended, or suggested in the and that
may be new chemical formula or an established drug prescribed for use in new
way.
A new substance of chemical, biological, or biotechnological origin in bulk or
prepared dosage form used for diagnosis, treatment, mitigation or prevention of
any disease or disorder in human or animal which except during local clinical
trial has not been used in the country to any significant extent and during local
clinical trials has not been recognized in the country as effective and safe for
the proposed claims.
Preclinical Testing :
A pharmaceutical company conducts laboratory and animal studies to show
biological activity of the compound against the targeted disease, and the compound is
evaluated for safety. These tests take approximately three and one-half years.
Investigational New Drug Application (IND):
After completing preclinical testing, the company files an IND with FDA to begin to
test the drug in people. The IND becomes effective if FDA does not disapprove it within
30 days.
The IND shows results of previous experiments, how, where and by whom the new
studies will be conducted; the chemical structure of the compound; how it is thought to
work in the body; any toxic effects found in the animal studies; and how the compound is
manufactured.
In addition, the IND must be reviewed and approved by the Institutional Review Board
where the studies will be conducted, and progress reports on clinical trials must be
submitted at least annually to FDA.
Clinical Trials, Phase I.
These tests take about a year and involve about 20 to 80 normal,
healthy volunteers. The tests study a drug's safety profile, including the safe
dosage range. The studies also determine how a drug is absorbed, distributed,
metabolized and excreted, and the duration of its action.
Clinical Trials, Phase II.
In this phase, controlled studies of approximately 100 to 300 volunteer patients
(people with the disease) assess the drug's effectiveness and take about two
years.
Clinical Trials, Phase III.
This phase lasts about three years and usually involves 1,000 to 3,000 patients in
clinics and hospitals. Physicians monitor patients closely to determine efficacy
and identify adverse reactions.
New Drug Application (NDA):
Following the completion of all three phases of clinical trials, the company analyzes
all of the data and files an NDA with FDA if the data successfully demonstrate safety
and effectiveness.
The NDA must contain all of the scientific information that the company has gathered.
NDAs typically run 100,000 pages or more.
By law, FDA is allowed six months to review an NDA. In almost all cases, the period
between the first submission of an NDA and final FDA approval exceeds that limit; the
average NDA review time for new molecular entities approved in 1992 was 29.9
months.
❖Approval.
Once FDA approves the NDA, the new medicine becomes available for physicians
to prescribe.
The company must continue to submit periodic reports to FDA, including any cases
of adverse reactions and appropriate quality-control records. For some medicines,
FDA requires additional studies (Phase IV) to evaluate long-term effects.
New Drug
Application
• The New Drug Application (NDA) is an application submitted to FDA
forpermission to market a new drug product.
• The goals of the NDA are to provide enough information to permit FDA
reviewers to establish the following:
1. Whether the drug is safe and effective in its proposed use(s), and
whether the benefits of the drug outweigh the risks?
2. Whether the drug's proposed labeling appropriate, and what should it
contain?
3. Are the methods used in manufacturing (Good Manufacturing Practices;
GMP) of the drug and the controls used to maintain the drug's quality
adequate to preserve the drug's identity, strength, quality, and purity?
Drug Development Process
Objective of NDA
Whether the drug's proposed labeling (package insert) is
appropriate, and what it should contain.
Whether the drug is safe and effective in its propose use,
and whether the benefits of the drug outweigh the risks.
Whether the methods used in manufacturing the drug and
the controls used to maintain the drug's quality are
adequate to preserve the drug's identity, strength, quality,
and purityNDA (Abky Lumagariya)10
NDA Form
FDA-356h. Application to market a new drug, biological or an
antibiotic drug for human use.
Form FDA 3397. User fee cover sheet.
Form FDA 3331. New drug application field report.
Impurity in drug substances.
Required specification for FDAs IND, and ANDA drug master file
binders.
Refusal to file.
Requirement
No of copies –
Before 1985-3 copies & now only 2 copies.
1) Archival copy
Reference copy for FDA (i.e. retained by FDA)
Locate information not contained in review copy2)
2)Review copy
Divided in to five or six section containing technical and
scientific information separately bound
It contains copy of cover letter, application form, overall
summary, index, specific review section
Summary requirement
1) Labeling:
- Proposed label
- It is also called mini summary
2) Pharmacological class
- Intended use
- Potential clinical benefit
3) Foreign marketing history
- List of country who approved same drug
-List of country who withdrawn same drug
4) Chemistry, mfg., control
A) Drug substanceNames:-
- name, synonym, code designation, brand name, identification no. and chemical name.
- Physical and chemical properties: MP, BP, mol wt., solubility, mol. Formula structural
formula, PH, isomer, polymorphs.
- Stability
- Manufacture-Name and method.
B) Drug product.
I Composition
II. Dosage form
III. Manufacture
IV. Specification
V. Analytical method
VI. Container
VII. Closure
VIII. Stability
IX. Investigational formulation
5) Nonclinical pharmacology and toxicology summary
Pharmacological studies
Acute toxicity studies
Multi dose toxicity studies
Mutagenicity studie
Reproduction studie
ADME studies
6)Human pharmacokinetics summary
7)Microbial summary
8) Clinical data summary and result
A) Clinical pharmacology
B) Overview of clinical studies
C) Controlled clinical studie
D) Uncontrolled clinical studies
E) Other studies and information
F) Safety summary
a) Extent of exposure
b) Adverse event
c) Clinical laboratory data
d) Over dose
e) drug abuse
9) Discussion of benefit to risk relationship and
proposed
10) Bioavailability summary
NDA technical section requirement
1) Chemistry, manufacturing, and control
a) Drug substance
b) Product
2) Non clinical pharmacology and toxicology
3) Human pharmacokinetics
4) Bioavailability section
5) Microbiology
a) Mechanism of action
b) Pharmacokinetics
c) Antimicrobial activity
d) Enzyme hydrolysis rate
e) Assessment of resistance
f) In vivo animal studies
g) In vitro studies during clinical trial
h) Published literature
i) Miscellaneous studies
6) Clinical data section
adverse dose- response information
drug-drug interaction
drug disease interaction
Other NDA requirement
-Safety
Reference :-
A textbook of regulatory affairs Mayur S. Jain , Dr. Md. Rageeb Md. Usman Dr. S.
D. Barhate Dr. Sunil Kumar Shah.
Prescription New Drug Submission, Regulatory Affairs Prutiessional Society,
2000.57-71
Richard A. Guarino and Marcel Dekkar. New Dni Approva Marcel Dekkar. New Drug
Approval Process, 2nd edition, 1987,39-91
Howard C. Ansed Pharmaaceutical Dosage Forms and Drug Delivery System, Ath
edition, 200 62.
www.fda.gov/oder/regulatory/applications/ind_page_1.htm
www.ida.gov/cder/ddms/binders.him
Remington, The Science and Practice of Pharmacy 21st edition, Volume-1,965
www.fda.gov/cder/guidance/2125inl.htm
