The document discusses the process for submitting a New Drug Application (NDA) for regulatory approval globally. An NDA is submitted to agencies like the FDA or DCGI in India to gain approval to market a new drug after Phase III clinical trials. The application contains extensive information on the chemistry, manufacturing, nonclinical and clinical data that supports the drug's safety and efficacy. Regulatory agencies thoroughly review the NDA and may approve the drug, approve it conditionally, or refuse approval depending on their evaluation. The review process involves multiple steps and communication between the drug sponsor and agency.

1. REGULATORY AFFAIRS
NON CLINICAL DRUG DEVELOPMENT:
GLOBAL SUBMISSION OF NDA
Presented by
ABDUL NAIM
M.Pharm Pharmaceutics Department
Nargund college of pharmacy

2. NEW DRUG APPLICATION (NDA):
The New Drug Application is the vehicle through which the drug
sponsors formally propose FDA or DCGI to approve a new
investigational drug for sale and marketing after phase IIIA Pivot
trials.
The official definition of New Drug is in sec 201(p) of Federal Drug,
Food and Cosmetics Act as;
Any new drug, the composition of which is such that it is not
recognized among experts qualified by scientific training as safe and
effective for use under prescribed, recommended or suggested
conditions.

3. The following letter codes describe the review priority of the drug;
S-Standard review:- For drugs similar to currently available drug.
P-Priority review:- For drugs that represent significant advances over
existing treatments.
Classification of drugs in NDA:-
Center of drug evaluation and research (CDER) classifies new drug
applications according to the type of drug being submitted and its intended
use;
A) New molecular entity.
B) New salt of previously approved drug.
C) New formulation of previously approved drug.
D) New combination of two or more drug.
E) Already marketed drug product-Duplication.

4. F) New indication (claim) for already marketed drug.
G) Already marketed drug product (no previous approved NDA)
In US following 4 type of applications are submitted for approval of drug for
marketing depending upon the type and nature of the drug;
A) New drug application (NDA).
B) Biological License Application (BLA).
C) Application u/s 505(b)(2) Paper NDA.
D) Supplemental New Drug Application (SNDA).

5. FORMAT and content of NDA:-
The application is required to be submitted in common technical document
format with the following different sections;
1. FDA from 356h
2. User free cover sheet (FDA from 3397)
3. Cover latter (comprehensive table of contents for modules 1 to 5)
4. Summary
5. Chemistry, Manufacturing and Control
6. Samples, method validation package and labeling
7. Nonclinical pharmacology and toxicology
8. Human pharmacokinetics and bioavailability

6. 9. Microbiology (for anti-microbial drugs only)
10. Statistical methods and analysis of clinical data
11. Safety update report (typically submitted 120 days after NDA submission)
12. Statement regarding compliance to IRB and Informed Consent
requirements
13. Case Report Tabulations
14. Case Report Forms
15. Patent information and certification
16. Other information

7. General requirements for filing NDA:-
The new NDA regulations require the application to be submitted in 2
copies;
A) An Archival copy:- It is a complete copy of application submission that
serves as its permanent record.
B) A Review copy:- It is divided into 6 technical sections;
1. Chemistry, Manufacturing and Controls (CMC)
2. Nonclinical pharmacology and toxicology
3. Human pharmacokinetics and Bioavailability
4. Microbiology
5. Clinical data
6. Statistical

8. On receipt of NDA, the CDER stamps with a receipt dare to enable FDA to
forward action within 180 days called ‘Review Clock’ under Review Time
Frames (21 CFR 314.100).The FDA assigns the application for review.
The FDA has to intimate the applicant if it is incomplete within 60 days
according to Filing Time Frames (21 CFR 314.101).
FDA notifies the sponsor of its completion/ incompletion and if complete
sends it for secondary review process.
FDA inspects the manufacturing facilities for the drug, it may also inspect
sample of clinical trial locations to verify the accuracy of data submitted.

9. NDA REVIEW CHART

10. Throughout the process FDA and sponsor communicate through in
person meetings, telephone conferences, fax etc… to seek clarification if
necessary. Once all reviews are complete; the divisional director
evaluates the reviews and makes FDAs decision.
The FDA MAY;
• Approve the drug for marketing.
• Approve the drug with condition when problem exist with the
application that needs to be addressed before approval.
• Refuse to approve the drug, when it may require additional research or
reformulation of the drug product.

11. NDA PROCESS IN INDIA:-
In India, New Drug is defined under Rule 122-E of Drugs and Cosmetics
Act as;
A) A drug which has not been used in the country to any significant
extent under various conditions.
B) A drug already approved by DCGI for certain claims which is now
proposed to be marketed with new claims like indications, dosage,
dosage form etc…
C) A fixed dose combination of two individually approved drug being
combined for the first time in a fixed ratio or new ratio in already
marketed combination.
D) All vaccines are considered as new drugs.
E) A new drug continues to be considered as new drug for a period of 4
years from its approval or its inclusion in India Pharmacopoeia.

12. After successful finishing of clinical trials, the applicant seeking for
approval to manufacture a new drug requires to submit application on
form 44 along with data as given in Appendix I to Schedule Y of Rules 1945
to DCGI who grants its approval in form 46 or 46-A.
Further, the applicant is required to submit evidence that the drug for
manufacturing approval already has been approved by DCGI.
In his name while applying to manufacture a new drug to State Licensing
Authority. Thus the applicant is required to obtain necessary approval
from DCGI as well as SLA for manufacturing a new drug for sale purposes
in India.
The approval issued is ‘manufacture for sale’ rather than ‘marketing
approval’ as per the practice world over.

13. PERMISSION TO MANUFACTURE A NEW DRUG:-
• Brief introduction of the new drug.
• Chemical and pharmacological information.
• Animal pharmacology and toxicology.
• Human/ clinical pharmacology (phase I).
• Exploratory clinical trials (phase II).
• Confirmatory clinical trials (phase III).
• Bio-availability, dissolution and stability study data.
• Regulatory status in other country.
• Application for test license.
• Marketing information.