1.

Applicant or Drug Sponsor

a. is the person or entity who assumes responsibility for the marketing of a
new drug
b. Usually an individual, partnership, corporation, government agency,
manufacturer or scientific institution.

• Full drug marketing application submissions under 21 CFR subpart 314.50 and
314.54 should be directed to:
Center for Drug Evaluation and Research
Food and Drug Administration
Document and Records Section
5901-B Ammendale Rd
Beltsville, Md. 20705-1266
2. NDA (New Drug Application)
a. Since 1938, every new drug has been the subject of an approved NDA before
U.S. commercialization.
b. 1938, NDAs were only required to contain information pertaining to the
investigational drugs safety
c. 1962, the Kefauver-Harris Amendments to the FD&C Act required NDAs to
contain evidence that a new drug was effective for its intended use and the drugs
safety
d. 1985,the Fundamentals of NDA Submissions was established
1. Index;
2. Summary;
3. Chemistry, Manufacturing, and Control;
4. Samples, Methods Validation Package, and Labeling;
5. Nonclinical Pharmacology and Toxicology;
6. Human Pharmacokinetics and Bioavailability;
7. Microbiology (for anti-microbial drugs only);
8. Clinical Data;
9. Safety Update Report (typically submitted 120 days after the NDA's
submission);
10. Statistical;
11. Case Report Tabulations;
12. Case Report Forms;
13. Patent Information;
14. Patent Certification; and
15. Other Information.
e. NDA Content and Format Requirements
i. NDA must provide all relevant data and information that a sponsor has
collected during the product's research and development.
f. NDA Classifications
i. CDER classifies new drug applications with a code that reflects both the
type of drug being submitted and its intended uses. The numbers 1 through 7 are
used to describe the type of drug

1- New Molecular Entity

2- 2- New Salt of Previously Approved Drug (not a new molecular entity)
3- 3- New Formulation of Previously Approved Drug (not a new salt OR a new
molecular entity)
4- 4- New Combination of Two or More Drugs
5- 5- Already Marketed Drug Product - Duplication (i.e., new manufacturer)
6- 6- New Indication (claim) for Already Marketed Drug (includes switch in
marketing status from prescription to OTC)
7- 7- Already Marketed Drug Product - No Previously Approved NDA
3. Is the Application Fileable?
a. Evaluation ensures that sufficient data and information have been submitted
in each area to justify "filing" the application
i. No: Refuse-to-File Letter Issued
1. The applicant receives a letter detailing the decision and the deficiencies
that form its basis. This decision must be forwarded within 60 calendar days after
the NDA is initially received by CDER
4. If the Application is Fileable it is reviewed by CDER
a. Medical Review
i. Medical reviewers are responsible for evaluating the clinical sections of
submissions, such as the safety of the clinical protocols in an IND or the results
of this testing as submitted in the NDA.
ii. Conducted by medical officers (mostly physicians)
b. Biopharmaceutical Review
i. Pharmacokineticists evaluate the rate and extent to which the drug's active
ingredient is made available to the body and the way it is distributed in,
metabolized by, and eliminated from the human body
c. Pharmacology/Toxicology Review
i. Conducted by pharmacologists and toxologists
ii. They evaluate the results of animal testing and attempt to relate animal
drug effects to potential effects in humans
d. Statistical Review
i. Performed by Statisticians
ii. Evaluate the statistical relevance of the data in the NDA
1. Purpose of evaluation
1- Give the medical officers an idea of the power of the findings
2- How this information should be distributed to the larger patient population
e. Chemistry Review
i. Performed by Chemists
ii. Issues addressed
1. Drug identity
2. Manufacturing control
3. Analysis
4. Potential human risks should be listed by the manufacturer and tested by the
chemists
f. Microbiology Review
i. This review is required only in NDAs for anti-infective drugs
ii. These drugs affect microbial physiology so in vivo and in vitro effects
should be tested
iii. Known resistance mechanisms and factors should be stated
5. Outside influence on approval: Advisory Committees
a. The CDER uses advisory committees to obtain additional opinions, advice,
ideas, etc.
i. This allows for a larger expert input
b. All opinions, advice, ideas etc, are not obligatory
c. Advisory committees are asked to place their input on the following
i. New drugs
ii. Already approved drugs
iii. Labeling information
iv. Guideline alterations
v. Effectiveness
vi. Marketing approvals and methods
6. How is the sponsor included during the CDER review process?
a. The CDER communicates with the sponsor during the review process
i. Scientific, medical, procedural issues
ii. Communication occurs via telephone, letters, faxes, or meetings
b. If more data is needed or technical changes are necessary the CDER informs
the sponser
7. How is the sponsor notified regarding the outcome of their drug evaluation
by the CDER?
a. The sponsor is sent one of three possible action letters from the CDER after
the review process is complete
i. Not Approval Letter
1. Lists deficiencies in application
2. Explanation of disapproval
ii. Approvable Letter
1. The drug can be approved
2. Lists minor deficiencies
3. Post-approval studies
iii. Approval Letter
1. The drug is approved
b. Regardless of issued action letter the sponsor has an opportunity to meet
with the CDER agency upon request
8. NDA Actions
a. Once the action letter recommendation is decided by the reviewers and
supervisors the decision must be evaluated and agreed on by the director of the
drug review division.
b. The consumer safety officer assembles an “action package” which includes
i. The action letter
ii. Any data
iii. CDER reviews and memos
c. Final FDA ruling
i. Division director usually has the ‘sign-off’ of such drugs
ii. Class I drugs require a office level (above division director) ‘sig-off’
iii. After the approval action letter is signed by the division or office
director the product can be legally marketed starting that day in the United
States