This document provides an overview of regulatory requirements for drugs and pharmaceuticals. It discusses drug regulation by international agreements and regulatory authorities like the FDA. The FDA is organized into centers responsible for drugs, biologics, devices and food. Applications like IND, NDA, ANDA are described which are required for investigational and approved drugs. The new drug approval process is outlined involving pre-clinical and clinical testing taking 10+ years. Key differences between NDA for new drugs and ANDA for generic drugs are summarized.

1. REGULATORY REQUIREMENTS OF
DRUGS AND PHARMACEUTICALS
BY:-
Abhinab Goswami
M.Pharm 1st sem

2. DRUGS REGULATION
Drug regulation is the control of drug use by
international agreement and/or by regulatory
authorities such as the US Food and Drug
Administration (FDA), the European Medicinal
Agency (EMA) and the Japanese Pharmaceutical and
Medical Devices Agency (PMDA). This includes
regulations concerned with the development,
approval, manufacturing and marketing of drugs.

3. FDA Role and Organization
• FDA is organized into a number of offices and centers headed
by a commissioner who is appointed by the President with
consent of the senate
• These offices and centers are assigned with different
responsibilities to accomplish the objective of FDA
1. Center for Drug Evaluation and Research (CDER)
2. Center for Biologic Evaluation and Research (CBER)
3. Center for Devices and Radiological Health (CDRH)
4. Center for Food Safety and Applied Nutrition (CFSAN)
5. Center for Veterinary medicine (CVM)

4. TYPES OF APPLICATIONS
• Investigational New Drug Application
• New Drug Application
• Abbreviated New Drug Application
• Biologic License Application
• Over-the-counter (OTC) drug application

5. Clinical Hold
IND Filing
IND Approval
Drug Discovery
and
Lead Compound
Selection
Biologic
Activity testing
(in vivo)
Formulation
development and
stability
Chemical Synthesis
and Scale up testing
Safety Testing in
Animals
IND Application
Phase I Clinical trials Phase II Clinical trials
Phase III Clinical
trials
NDA Filing
FDA Disapproval FDA Conditional
Approval
FDA Approval
MARKET
Post-Approval Safety
report to FDA
PRE-CLINICAL TESTING
(4+ YEARS)
CLINICAL TESTING
(6+ YEARS)
Fig: the new drug approval process
Revision
Revision

6. Investigational New Drug (IND)
• It deals with a new chemical entity, which will be tested for
obtaining evidence of safety and effectiveness in accordance
with the regulation. It is the vehicle through a new drug
advances into next stage of drug development i.e. Clinical
trials

7. Types of INDs
1. Investigator IND:- It is submitted by a physician who initiates
and conducts an investigation, and under whose immediate
direction the investigational drug is administered or
dispensed. A physician might submit a research IND to
proposed studying an unapproved drug, or an approved
product for a new indication or in a new patient population.
2. Emergency Use IND:-This allow the FDA to authorize an
experimental drug in an emergency situation that does not
allow for submission of an IND in accordance with 21CFR,
Sec. 312.23 0r Sec.312.20. It is also used for patient who do
not meet the criteria of an existing study protocol, or if an
approved study protocol does not exist.

8. 3. Treatment IND:- It is submitted for experimental drugs
showing promise in clinical testing for serious or immediately
life-threatening conditions while the final work is conducted
and the FDA review takes place.

9. Investigational New Drug Application

10. Criteria for application
• A clinical study is required for an IND if it is intended to
support a:
– New Indication.
– Change in the approved route of administration or dosage
level.
– Change in the approved patient population or a population
at greater or increased of risk .
– Significant change in the promotion of an approved drug

11. Application Content
• Animal Pharmacology and Toxicology studies.
• Chemistry and Manufacturing Information.
• Clinical Protocols and Investigator
Information.

12. NEW DRUG APPLICATION (NDA)
• The New Drug Application (NDA) is the vehicle in the United
States through which drug sponsors formally propose that the
FDA approve a new pharmaceutical for sale and marketing. NDA is
responsible for are providing enough information to permit FDA
reviewers to establish the following:
– Whether the drug safe and effective in its proposed use(s)
when used as directed, and do the benefits of the drug
outweigh the risks.
– Whether the drug’s proposed labeling (package insert)
appropriate, and what should it contain.
– Whether 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.

14. Fundamentals of NDA Submission
• As outlined in Form FDA-356h, Application to Market a New
Drug for Human Use Or As An Antibiotic Drug For Human Use,
NDAs can consist of as many as 15 different sections:
– Index
– Summary
– Chemistry, Manufacturing, and Control;
– Samples, Method Validation Package, and Labeling
– Nonclinical Pharmacology and Toxicology
– Human Pharmacokinetics and Bioavailability
– Microbiology (for anti-microbial drugs only);

15. – Clinical Data;
– Safety Update Report (typically submitted 120 days after
the NDA's submission);
– Statistical;
– Case Report Tabulations;
– Case Report Forms;
– Patent Information;
– Patent Certification; and
– Other Information

16. Classification of drugs in NDA
CDER classifies new drug applications with a code that
reflects both the type of drug being submitted and its
intended uses.
– New Molecular Entity
– New Salt of Previously Approved Drug (not a new molecular
entity)
– New Formulation of Previously Approved Drug (not a new salt
OR a new molecular entity)
– New Combination of Two or More Drugs
– Already Marketed Drug Product - Duplication (i.e., new
manufacturer)
– New Indication (claim) for Already Marketed Drug (includes
switching marketing status from prescription to OTC)
– Already Marketed Drug Product - No Previously Approved NDA

17. GENERAL REQUIREMENTS for filing an
NDA
• The new (present) NDA regulations require that an application be
submitted in two copies :
(A) an archival copy that serves as a permanent record of the
submission, and
(B) a review copy.
– The review copy is made up of a number of separate technical
volumes, each tailored to the needs of the disciplines involved in the
review.
– Both the archival and review copies are submitted in hard copy, the
regulations permit an application to submit the archival copy as
microfiche.
– The NDA application form (FORM FDA 356h ) consists of: Twelve items
(including index) deals with the safety and efficacy features of drug
product, two are concerned with patent information

18. • The archival copy is a complete copy of an application
submission and must be bound in a blue cover jacket.
• The archival copy should include a blue cover letter to:
– Confirm any agreement or understanding between the
FDA and the agreement;
– Identify the contact person regarding the application
– Identify the reviewing division of the FDA and include HFD
number;
– Convey any other important information about the
application.

19. REVIEW SECTION COLOUR CODE
(i) Chemistry, Manufacturing and Controls (CMC) RED
(ii) Nonclinical Pharmacology and Toxicology YELLOW
(iii) Human Pharmacokinetics and Bioavailability ORANGE
(iv) Microbiology (if required) WHITE
(v) Clinical Data LIGHT BROWN
(vi) Statistical GREEN
The review copy is divided into six technical sections (“review sections”) and
should be submitted with each review section separately bound in a specific
color:

20. • Each review section should contain the
following:
(i) a copy of the cover letter attached to the archival
copy;
(ii) a completed application form FDA 356h;
(iii) a copy of the summary (defined below);
(iv) a copy of the general index of the entire application;
(v) an index specific to that particular review section;
(vi) letters of reference or authorization, if appropriate;
(vii) patent information

21. ABBREVIATED NEW DRUG APPLICATION
• In addition to approving new drug products , the FDA
is charged with the approval of generic products (21
CFR 314), which is accomplished through CDER’s
Office of Generic Drugs.
• An Abbreviated New Drug Application (ANDA)
contains data submitted to FDA's Center for Drug
Evaluation and Research, Office of Generic Drugs, for
review and ultimate approval of a generic drug
product.
• The reviewing process for generic drug is focused on
bioequivalence testing rather than safety and
efficacy.

22. • To be considered bioequivalent, both rate and extend
of drug absorption must be within established
parameter in comparison to the reference drug.
• Use of bioequivalence as the base for approving
generic drug products was established by the "Drug
Price Competition and Patent Term Restoration Act
of 1984," also known as the WAXMAN-HATCH ACT.

24. Guidelines available for ANDA:
• Various guidelines have been developed to assist
applicants in preparing and filing ANDAs
• Format & content for the following sections:
a. Application summary
b. Chemistry, Manufacturing and controls section
c. Non clinical pharmacology and toxicology section
d. Human pharmacokinetics & bioavailability section
e. Clinical and statically section
f. Microbiology section

25. ANDA requires the submission of :
• Detailed descriptions of the components
• Manufacturing, controls, packaging, and labeling
(which can be in final, printed form), data
sufficient to assure the bioavailability or
bioequivalence of the drug to be marketed.
• The labeling should be prepared in accordance
with that specified in DESI (Drug efficacy study
implementation) Notice or other Federal
Register

26. NDA ANDA
Applicable for new drug Applicable for generic drug
Take longer time ( 12-15 years) Compare to NDA less time
taken(1-2 years)
More expenditure of money Comparatively less
Cost of drugs are more Cost of drugs are less
Nonclinical studies and clinical
investigations are essential
Nonclinical studies and clinical
investigations are nonessential
except bioavailability and
bioequivalence
COMPARISON

27. REFERENCES
1. The theory and practice of Industrial
Pharmacy ,Leon Lachman and Herbert A.
Lieberman Indian Edition 2009,page no. 856-
871
2. The Science and Practice of Pharmacy,
Remington 21st Edition, Volume 1 . Page no
965-975.
3. http://www.fda.gov/AboutFDA/Transparency
/Basics/ucm194879.htm

28. Thank You