The slides present brief overview of FDA drug approval and review process for NDA.

1. STAGES OF DRUG DEVELOPMENT AND REVIEW: SIMPLIFIED
- Nigar Fatima
M.Pharmacy (Regulatory Affairs)
MCOPS

2. DISCOVERY OF DRUG AND ITS SCREENING
The first step is obviously
the discovery of a
promising lead new
chemical entity, after
screening thousands of
molecules.
The sponsors (companies,
research institutions, and
other organizations) must
test the new drugs on
animals for toxicity.
Multiple species are used
to gather basic information
on safety and efficacy of
the molecule/ entity being
investigated/ researched.
Investigational New Drug
(IND) application is then
submitted to the FDA
which has the animal
results based on initial
testing such as drug’s
composition,
manufacturing, safety in
animals, and based on
these results the sponsor
develops a plan for testing
the drug on humans.
At this stage, FDA and
Institutional Review Board
(IRB) reviews IND and
clinical trial protocol to
ensure that clinical trials
would in no possible way
put human candidates at
unreasonable risk. Also,
very crucial to the eyes of
FDA is that trial subjects
have submitted voluntary
informed consent form
prior to participation.

3. CONDUCTING TRIALS ON HUMAN SUBJECTS
PHASE 1 TESTING
(20-80): Usually
conducted in healthy
volunteers,
emphasizing on safety
of drug. The goal is to
identify the drug’s
most frequent side
effects and how the
drug is metabolized
and excreted.
PHASE 2 TESTING (100’s):
Performed if Phase 1 studies
don't reveal unacceptable
toxicity. The phase emphasizes
on effectiveness by studying if
at all the drug works in people
who have a certain disease or
condition. For controlled trials,
patients receiving the drug are
compared with similar patients
receiving a different treatment
(placebo), or a different drug.
• At the end of this phase, one
of the two most common
meeting is held between FDA
and sponsor on designing
phase 3 trials.
PHASE 3 TESTING
(1000’s): If evidence
of effectiveness is
gathered in Phase 2,
then studies are
done in different
populations and
different dosages
and using the drug in
combination with
other drugs.

4. FDA’s REVIEW OF NEW DRUG APPLICATION:
A team of CDER physicians, statisticians, chemists, pharmacologists, and other scientists review the drug sponsor’s
data and proposed labelling of drugs.
DRUG LABELLING: FDA reviews the drug’s label artwork to ensure appropriate information is communicated to
healthcare professionals and consumers
.
APPLICATION REVIEW: FDA has 60 days to decide whether to file sponsor’s NDA so that it can be reviewed. If
FDA files it, the FDA Review team will be assigned to evaluate all animal and human data and analyses of the data
for safety and effectiveness for its proposed use.
The review period lasts from 6-10 months. CDER expects to review and act on at least 90 percent of NDAs for
standard drugs no later than 10 months after the applications are received. The review goal is six months for priority
drugs.

5. NDA APPLICATION: A formal step wherein, sponsor submits NDA for approval by FDA in order to market the
drug in the U.S.
REVIEW MEET: This is the pre-NDA meet between the drug sponsor and FDA.
FACILITY INSPECTION: Another aspect the approval process of NDA is also an inspection of the
manufacturing facilities by FDA, for checking its compliance with cGMP.
FDA DRUG APPROVAL: After thorough analysis by FDA reviewers, they will either approve NDA or issue a
response letter.

6. CONCEPT OF ACCELERATED AND FAST TRACK APPROVALS
• Traditional approval demands evidence for clinical benefit (clinical end point) to be shown prior to an approval
being granted. However, for some drugs that treat serious diseases and fill unmet medical needs, FDA
provides accelerated approval by basing the drug’s effectiveness on a “surrogate end point”, such as
shrinking of tumor or reduction in cholesterol, rather than waiting for clinical trial results.
• In case of a Fast track approval, the time taken by FDA to review those drugs treating serious, life threatening
diseases and fill unmet needs, is shortened. Sponsors can submit portions of an application as and when
information becomes available – called “Rolling submission”, rather than waiting for complete clinical
information to be made available.

7. HURDLES IN
DRUG APPROVAL
PROCESS
If there are issues
with an NDA or if
more information is
necessary to make a
determination that
benefits outweigh
risks, then FDA
issues a complete
response letter.
There might be
unexpected safety
issues or failure to
demonstrate a drug's
effectiveness or
manufacturing
deficiencies which
needs to be
addressed for getting
FDA’s approval.
FDA will outline the
justification for its
decision in a
complete response
letter to the drug
sponsor and CDER
gives the sponsor a
chance to meet with
agency officials to
discuss the
deficiencies.

8. THE USER FEES – PRESCRIPTION DRUG USER FEES ACT
Since PDUFA was passed in 1992, more than 1,000 drugs and biologics have come to the market, including
new medicines to treat cancer, AIDS, cardiovascular disease, and life-threatening infections.
PDUFA has allowed the FDA to bring access to new drugs as fast or faster than anywhere in the world, while
maintaining the same thorough review process.
Under PDUFA, drug companies agree to pay fees that boost FDA resources, and the FDA agrees to time
goals for its review of new drug applications.

9. CHECKING THE QUALITY OF CLINICAL DATA SUBMITTED
The FDA relies on clinical data
submitted by sponsor to decide
whether a drug should be approved.
In order to protect the rights and
welfare of subjects in clinical trials,
and to verify the quality and integrity
of data submitted, the FDA's
Division of Scientific Investigations
(DSI) conducts inspections of
clinical investigators' study sites.
DSI also reviews the records of IRB
to ensure patient protection.
In case of deviations, such as
falsification of data, DSI sends a
warning letter or Notice of Initiation
of Disqualification Proceedings and
Opportunity to Explain (NIDPOE) to
the clinical investigator.
The FDA has also established an
independent Drug Safety Oversight
Board (DSOB) to oversee the
management of drug safety issues.

10. FDA’s POST
APPROVAL
RISK
ASSESSMENT
SYSTEM
• PHASE 4 TESTING: Postmarket
requirement and commitment
studies are agreed to by a
sponsor, and are conducted after
the FDA has approved a product
for marketing. The FDA uses
postmarket requirement and
commitment studies through
Periodic Safety Update Report
(PSUR), to gather additional
information about a product's
safety, efficacy, or optimal use.
• MEDWATCH: FDA’s MedWatch
is a voluntary system to report
adverse events. The physicians
and public get informed of any
important new risks that are
uncovered via the updated drug
labelling as well as via letters,
public health advisories and other
education.

11. REFERENCES:
https://www.fda.gov/drugs/drug-information-consumers/fdas-drug-review-process-ensuring-drugs-
are-safe-and-effective (Accessed)