1. NEW DRUG APPLICATION

2. DRUG APPROVAL PROCESS
A Regulatory process by which a person/organization/sponsor/innovator gets authorization to launch a new drug in the market is known as drug approval process
NEW DRUG APPROVAL:
A submission to the USFDA or concerned regulatory authority of the country containing clinical and non-clinical teat data/analysis reports along with drug chemistry information

3. INTRODUCTION
The FDA has established guidelines for formatting, assembling & submitting the NDA
Failure to follow these guidelines can result in deficiencies that could
▪Delay review
▪Require an amended application
▪Result in a refusal to file
• NDA shares most common elements with the CTD developed by the ICH

4. INTRODUCTION
The new drug application(NDA) is a critical component in the drug approval process
The NDA contains
Clinical and non-clinical test data and analyses
Drug chemistry information
Descriptions of manufacturing procedures
An NDA consists of thousands of pages of information to be reviewed by FDA teams composed of highly qualified individuals with expertise in their respective technical fields

5. INTRODUCTION
Usually six different teams are responsible for reviewing an NDA
The teams are organized by technical reviewing responsibilities
▪Clinical
▪Pharmacology/Toxicology
▪Chemistry
▪Statistics
▪Biopharmaceutical &
▪Microbiology

6. NDA GOALS
The goals of the NDA are to provide enough information to permit FDA reviewers to establish the following:
Is the drug safe and effective in its proposed use(s) when used as directed, and do the benefits of the drug outweigh the risks?
Is the drug’s proposed labeling (package insert) appropriate, and what should it contain?
Are the methods used in manufacturing (Good Manufacturing Practice, GMP) the drug and the controls used to maintain the drug’s quality adequate to preserve the drug’s identity, strength, quality, and purity?

7. NDA COPIES
FDA requires drug sponsors to submit multiple copies of the NDA 1 ARCHIVAL COPY: ◊ The cover letter, ◊The administrative section ◊It must contain four copies of labeling section ◊It must contain three additional copies of CMC and methods validation package in a separate binder ◊Only copy that contains the case report tabulation and case report forms

8. NDA COPIES
2 REVIEW COPY: It contains the NDA’s technical sections along with the cover letter, form FDA-356 h, NDA index as well as individual table of content, the labeling section and application summary 3FIELD COPY: Its required by FDA inspectors during pre-approval facilities inspection. In addition to content of review copy includes CMC and methods validation package

9. NDA CONTENTS NDA Section 1: Index NDA Section 2: labeling
NDA Section3: application summary
NDA Section 4: Chemistry , Manufacturing, controls (CMC)
NDA Section 5: Non-clinical pharmacology and Toxicology
NDA Section 6: Human pharmacokinetics and Bioavailability
NDA Section 7: Microbiology
NDA Section 8: clinical data
NDA Section 9: Safety Update Reports

10. NDA CONTENTS NDA Section 10: Statistics
NDA Section 11: Case Report Form Tabulations
NDA Section 12: Case Report Forms
NDA Section 13: Patent Information
NDA Section 14: Patent Certification
NDA Section 15: Establishment Description
NDA Section 16: Debarment Certificate
NDA Section 17: Field Copy Certification
NDA Section 18: User Fee Coversheet
NDA Section 19: Financial Disclosure
NDA Section 20: others

11. BEFORE TRIALS
To legally test the drug on human subjects in the U.S., the maker must first obtain an Investigational New Drug (IND) designation from FDA. This application is based on pre-clinical data, typically from animal studies after P1, that shows the drug is safe enough to be tested in humans.
Often the "new" drugs that are submitted for approval include new molecular entities or old medications that have been chemically modified to elicit differential pharmacological effects or reduced side-effects.

12. CLINICAL TRIALS
The legal requirement for approval is "substantial" evidence of efficacy demonstrated through controlled clinical trials.
This standard lies at the heart of the regulatory program for drugs.
It means that the clinical experience of doctors, the opinion of experts, or testimonials from patients, even if they have experienced a miraculous recovery, have minimal weight in this process.
Data for the submission must come from rigorous clinical trials

13. CLINICAL TRIALS The trials are typically conducted in three phases:
PHASE 1: The drug is tested in a few healthy volunteers to determine if it is acutely toxic.
PHASE 2: Various doses of the drug are tried to determine how much to give to patients.
PHASE 3: The drug is typically tested in double-blind, placebo controlled trials to demonstrate that it works. Sponsors typically confer with FDA prior to starting these trials to determine what data is needed, since these trials often involve hundreds of patients and are very expensive.
(PHASE 4): These are post-approval trials that are sometimes a condition attached by the FDA to the approval.

14. CLINICAL TRIALS
If the FDA gives the green light, the "investigative" drug will then enter three phases of clinical trials:
PHASE 1: uses healthy volunteers to establish a drug's safety and profile. (about 1 year) 
PHASE 2: employs patient volunteers to assess the drug's effectiveness. (about 2 years) 
PHASE 3: involves patients in clinics and hospitals who are monitored carefully to determine effectiveness and identify adverse reactions. (about 3 years)

15. THE ACTUAL APPLICATION
The results of the testing program are codified in an FDA-approved public document that is called the product label, package insert or Full Prescribing Information.
The prescribing information is widely available on the web, from the FDA, drug manufacturers, and frequently inserted into drug packages.
The main purpose of a drug label is to provide healthcare providers with adequate information and directions for the safe use of the drug

16. THE ACTUAL APPLICATION
The documentation required in an NDA is supposed to tell the drug’s whole story, including what happened during the clinical tests, what the ingredients of the drug formulation are, the results of the animal studies, how the drug behaves in the body, and how it is manufactured, processed and packaged.
Currently, the decision process for FDA approval lacks transparency; however, efforts are underway to standardize the benefit-risk assessment of new medicines. Once approval of an NDA is obtained, the new drug can be legally marketed starting that day in the U.S.

17. THE ACTUAL APPLICATION
Once the application is submitted, the FDA has 60 days to conduct a preliminary review which will assess whether the NDA is "sufficiently complete to permit a substantive review". If the NDA is found to be insufficiently complete (and reasons for this can vary from a simple administrative mistake in the application to a requirement to re-conduct much of the testing). Then the FDA rejects the application with the issue of a Refuse to File letter which is sent to the applicant explaining where the application has failed to meet requirements.

18. THE ACTUAL APPLICATION
Assuming that everything is found to be acceptable, the FDA will decide if the NDA will get a standard or accelerated review and communicate the acceptance of the application and their review choice in another communication known as the 74-day letter
A standard review implies an FDA decision within about 10 months while a priority review should complete within 6 months.
Of original NDAs submitted in 2009, 94 out of 131 (72%) were in eCTD format.

19. THE ACTUAL APPLICATION
There is no requirement for any registration of a drug in India. However, there is need for approval from the Drug Controller of India (DCI) to import, market, or manufacture a “new drug.”
All new drugs (drugs not previously used in India or in use for less than four years) proposed to be introduced must be approved for import or manufacture in India by the DCI.
The application for permission to import or manufacture must be accompanied by the appropriate dossier as follows.

20. THE SET OF DATA TO BE SUBMITTED CONSISTS OF
Introduction: description of drug and therapeutic class
Clinical and pharmaceutical information
Animal pharmacology
Animal toxicology
Human/ clinical pharmacology (Phase I)
Exploratory clinical trials (Phase II)
Confirmatory clinical trials (Phase III)
Special studies
Regulatory status in other countries
Marketing information

21. SET OF DATA TO BE SUBMITTED
All items above may not be required for all drugs.
In case the drug is already approved and marketed abroad, then only Phase III trials may be required in India.
Further, such trials would need to be conducted on at least 100 persons spread over 3-4 locations in the country

22. DIFFERENT FEES CHARGED BY DRA in INDIA
Application by same applicant,                                   = Rs.15, 000/-
for modified dosage form or with new claim
Secondary applicants after 1                                       = Rs. 15,000/-
year of approval
Import / Mfg FDC                                                       = Rs. 15,000/-
Conduct Clinical trial with ND/IND
–Phase I                                                                      = Rs. 50,000/-
–Phase II                                                                     = Rs. 25,000/-
• –Phase III                                                                   = Rs. 25,000/-

23. Data Submitted Along With The Application
A. Permission to market new drug
1. Chemical and Pharmaceutical information
2. Animal Pharmacology
3. Animal Toxicology
4. Human / Clinical Pharmacology
5. Exploratory Clinical Trials
6. Confirmatory Clinical Trials
7. Bioavailability / dissolution and stability data
8 Regulatory status in other countries
9. Marketing information:
(a) Proposed product monograph
(b) Drafts of labels and cartons Application for test license :

24. B. Subsequent Approval / Permission For Manufacture Of Already Approved New Drug
a) Formulation:
Bioavailability / bioequivalence
Name of the investigator / centre
Source of raw material and stability
b) Raw Material
Manufacturing Method
QC parameters, specs, stability
Animal toxicity

25. C. Approval / Permission For FDC
Justification
PHARMACOKINETIC / Pharmacodynamic data
Any other data

26. Number and date of Approval already granted Justification
D. Subsequent Approval Or Approval For New Indication – New Dosage Form:
Number and date of Approval already granted
Justification
Data on safety, efficacy and quality

27. APPLICATIONS FILED IN INDIA
Yes, There are applications filed by industries.
Examples are:
Aurobindo (Zidovudine Tablets 60mg ((NDA ) and tentative approval for Lamivudine & Zidovudine Tablets 30mg / 60mg ((NDA ))
And Ranbaxy (oral controlled- release products ).

28. REFERENCES WWW.FDA.GOV WWW.medicalnewstoday.com www.drugs.com
NEW DRUG APPROVAL PROCESS by
RICHARD.A.GUARINO

29. THANKU