overview on all the aspects of United States Food and Drug Administration Regulatory Agency.

1. BY;
VENUGOPAL N
1 M-pharmacy
REGULATORY AFFAIRS
Dept. PHARMACEUTICS
JSS University
JSS College of Pharmacy, Ooty
An ISO 9001:2008 Certified Institution, Approved by
Pharmacy Council of India,
Approved by AICTE , Accredited 'A' Grade by NAAC

2. CONTENTS
 Introduction.
 History.
 Mission.
 Agency Review.
 FDA regulates.
 FDA doesn’t regulates.
 FDA Advisory committee.
 CFR.
 e-CFR.
 Orange book.
 IND.
 NDA.
 ANDA.
 Para IV certification.
 Hatch Waxman Act.
 Recall.
 Alert
 Warning letter.
 FDA Inspection.
 FDA Strategic Plan.
 Challenges faced by FDA.
 Laws enforced by FDA.
 FDA in India.
 Contacts.

3. U United
S States
F Food and
D Drug
A Administration
 Federal Agency of United States.
 Department of Health and Human Services.
 Formed in June 30 , 1906 (111 yrs)
 Founders : Theodore Roosevelt , Harvey Washington Wiley.
 Headquarters : white Oak Campus , 10903 New Hampshire Avenue ,
Silver Spring , Maryland.
 Executive agency
Scott Gottlieb , Commissioner of Foods and Drugs.
 Parent Agency
Department of Health and Human Services.

4. Website : www.fda.gov

5. HISTORY OF FDA
 Up until the 20th century, there were very few federal
laws regulating the sale of domestically produced food
and pharmaceuticals.
 In June 1906, President Theodore Roosevelt signed
into law the ‘Pure Food and Drug Act’
The Act applied penalties to the interstate marketing
of “adulterated” drugs in which the “Standard of
strength , quality or purity” of API was neither stated
clearly on the label nor listed in the USP or NF.
Also banned “misbranding” of food and drugs.

6.  In 1927, Bureau of Chemistry’s regulatory powers were
reorganized under a new USDA body, the Food, Drug
and Insecticide Organization.
 This name was shortened to the Food and Drug
Administration (FDA) three years later.
 June 24th, 1938 President , Franklin Delano Roosevelt
signed the new ‘Federal Food, Drug and Cosmetic Act
(FD&C Act) into law.

7. MISSION
 FDA is responsible for protecting the public health
by assuring the safety, efficacy and security
 FDA is also responsible for advancing the public
health by helping to speed innovations that make
medicines more effective, safer, and more
affordable
 Help the public get the accurate, science-based
information they need to use medicines and foods
to maintain and improve their health.
 FDA also has responsibility on tobacco products
to protect the public health and to reduce tobacco
use by minors.

8. FDA
ORGANIZATION
Centre for
Drug
Evaluation
and Research Centre for
Biological
Evaluation
and Research
Centre for
Devices
Radiological
Health
Centre for
Food Safety
and Applied
Nutrition
Centre for
Tobacco
Products
Centre for
Veterinary
Products
National
Center for
Toxicological
Research

9. What does FDA Regulates ?
 Foods, including:
• Dietary Supplements
• Bottled Water
• Food Additives
• Infant Formulas
 Drugs, including:
• Prescription Drugs (both brand-name and generic)
• Non-prescription (over-the-counter) drugs
 Biologics, including:
• Vaccines
• Blood and Blood Products
• Cellular and Gene therapy products
• Tissue and Tissue products
• Allergenic extracts

10. Medical Devices, including:
• Simple items like Tongue depressors and Bedpans
• Complex technologies such as Heart pacemakers
• Dental devices
• Surgical implants and Prosthetics
Electronic Products that give off radiation,
including:
• Microwave ovens
• X-ray equipment
• Laser products
• Ultrasonic therapy equipment
• Mercury vapor lamps
• Sunlamps

11. Cosmetics, including:
• color additives found in makeup
and other personal care products
• skin moisturizers and cleansers
• nail polish and perfume
Veterinary Products, including:
• livestock feeds
• pet foods
• veterinary drugs and devices
Tobacco Products, including:
• cigarettes
• cigarette tobacco
• roll-your-own tobacco
• smokeless tobacco

12. FDA does not regulates :
Advertising
The Federal Trade Commission is a federal agency that
regulates many types of advertising. The FTC protects
consumers by stopping unfair, deceptive or fraudulent
practices in the marketplace.
Alcohol
The Department of the Treasury’s Alcohol and Tobacco
Tax and Trade Bureau regulates aspects of alcohol
production, importation, wholesale distribution,
labeling, and advertising.

13. Consumer Products
The Consumer Product Safety Commission (CPSC)
works to ensure the safety of consumer products such as
toys, cribs, power tools, cigarette lighters, household
chemicals, and other products that pose a fire, electrical,
chemical or mechanical hazard.
Drugs of Abuse
The Department of Justice’s Drug Enforcement
Administration(DEA)works to enforce the controlled
substances laws and regulations of the United States,
including as they pertain to the manufacture,
distribution, and dispensing of legally produced
controlled substances.

14. Meat and Poultry
The U.S. Department of Agriculture's Food Safety and
Inspection Service regulates aspects of the safety and
labeling of traditional (non-game) meats, poultry, and
certain egg products.
Pesticides
The Environmental Protection Agency (EPA) regulates
many aspects of pesticides. EPA sets limits on how
much of a pesticide may be used on food during
growing and processing, and how much can remain on
the food you buy.

15. Vaccines for Animal Diseases
The U.S. Department of Agriculture’s Animal and
Plant Health Inspection Service (APHIS), Center for
Veterinary Biologics, regulates aspects of veterinary
vaccines and other types of veterinary biologics.
Water
The Environmental Protection Agency(EPA) regulates
aspects of drinking water. EPA develops national
standards for drinking water from municipal water
supplies (tap water) to limit the levels of impurities.

16. FDA Advisory Committee.
 Advisory committees provide FDA with independent
advice from outside experts on issues related to human
and veterinary drugs, vaccines and other biological
products, medical devices, and food.
 In general, advisory committees include a chair, several
members, plus a consumer, industry, and sometimes a
patient representative. Additional experts with special
knowledge may be added for individual committee
meetings as needed. Although the committees provide
advice to the agency, FDA makes the final decisions.

17. CFR
 The Code of Federal Regulations(CFR) is an annual
codification of the general and permanent rules
published in the Federal Register by the executive
departments and agencies of the Federal Government.
 The Code of Federal Regulations (CFR) is available:
As an electronic configuration, free of charge, on the
GPO's Federal Digital System (FDsys), maintained by the
U.S. Government Printing Office.
As paper publications, by full set subscription or
individual copy purchase, from the Superintendent of
Documents, or at any Federal Configuration Library.

18.  The CFR is divided into 50 titles representing broad
areas subject to Federal regulation.
 Each Title is divided into chapters that are assigned to
agencies issuing regulations pertaining to that broad
subject area. Each chapter is divided into parts and each
part is then divided into sections -- the basic unit of the
CFR.
 The purpose of the CFR is to present the official and
complete text of agency regulations in one organized
publication and to provide a comprehensive and
convenient reference for all those who may need to
know the text of general and permanent Federal
regulations.

19. Cont.,
21 CFR searchable database
 Parts 1 - 99 (product jurisdictions, protection of
human subjects, institutional review boards, etc)
 Parts 100 - 799 (food, human and animal drugs,
biologics, cosmetics)
 Parts 800 – 1299 (medical devices and radiation
emitting products)
 Parts 1300 - 1499 (controlled substances)

20. e-CFR
The Electronic Code of Federal Regulations (e-CFR) is a
currently updated version of the Code of Federal
Regulations (CFR).
It is not an official legal edition of the CFR.
The e-CFR is an unofficial editorial compilation of CFR
material and Federal Register amendments produced by
the National Archives and Records Administration's
Office of the Federal Register (OFR) and the
Government Printing Office.
The OFR updates the material in the e-CFR on a daily
basis. The current update status appears at the top of all
e-CFR web pages.

21. ORANGE BOOK
 The publication Approved Drug
Products with Therapeutic Equivalence
Evaluations (commonly known as the Orange Book)
identifies drug products approved on the basis of
safety and effectiveness by the Food and Drug
Administration (FDA) under the Federal Food, Drug,
and Cosmetic Act (the Act) and related patentable
data files are updated monthly. We make every effort
to prevent errors and discrepancies in the Approved
Drug Products data files.
 orangebook@fda.hhs.gov

23. IND Application
• Investigational New Drug Application.
• It is a submission to FDA requesting permission to
initiate the study of New drug product.
• It is the result of successful preclinical development
program.
• IND is a vehicle through which a sponsor advances to
the next stage of drug development known as Clinical
Trials ( Human trials).

24.  An IND would be required to conduct a Clinical trial if
the drug is –
-a new chemical entity not approved for the indication
under investigation in the new dosage form.
-in combination at the new dosage level.
- in combination with another drug and the
combination is not approved.
 The content & format of IND application is laid out in
CFR Title 21 part 312.

26. NEW DRUG APPLICATION
 Introduction
Critical component for drug approval process which
required to submit to USFDA before drug
commercialization.
FORM 44.
The data gathered during the animal studies and human
clinical trials of an Investigational New Drug (IND)
become part of the NDA.
 Goal
The NDA provide enough information to permit FDA
reviewer to reach safety, efficacy and quality for
pharmaceutical production. 26

27.  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 everything is found to be acceptable , the FDA will
decide if the NDA will get a standard or accelerated
review and communicate the acceptance and their
review choice in another communication known as 74
days later.
 A standard review implies an FDA decision within
about 10 months.

28.  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 switch in
marketing status from prescription to OTC)
 Already Marketed Drug Product - No Previously Approved NDA
28
NDA IS APPLICABLE FOR;

29. 29

30. NDA Review Process
30

31. ANDA
Abbreviated New Drug Application
“A drug product that is comparable to a brand/reference listed
drug product in dosage form, strength, route of administration,
quality and performance characteristics, and intended use”
It termed "abbreviated" because they generally not
required to include preclinical (animal) and clinical (human) data
to establish safety and effectiveness.
Basic Generic Drug Requirements are:--
 Same active ingredient(s)
 Same route of administration
 Same dosage form
 Same strength
 Same conditions of use
 Inactive ingredients already approved in a similar NDA
31

32. ANDA Review process
32

33. NDA vs. ANDA Review Process
NDA Requirement ANDA Requirement
33

34. Patent Certification condition for
ANDA
Described in section 505(j)(2)(A)(vii) of the Act.
 I Patent Not Submitted to FDA –
Approval effective after OGD scientific determination
 II Patent Expired –
Approval effective after OGD scientific determination
 III Patent Expiration Date (honored) –
Tentative approval after OGD scientific determination, final
approval when patent expires
 IV Patent Challenge –
Tentative approval after OGD science determination, final
approval when challenge won
OGD: Office Generic Drug
34

35. Paragraph IV certification
According to section 505(j)(2)(B)(i), 2157 CFR
 The ANDA applicant must provide appropriate notice of a
paragraph IV certification to each owner of the patent that
is the subject of the certification and to the holder of the
approved NDA to which the ANDA refers
And by Section 505(j)(5)(B)(iv)
 An incentive for generic manufacturers to file paragraph IV
certifications and to challenge listed patents as invalid, or
not infringed, by providing for a 180-day period of
marketing exclusivity
35

36. Patent Challenge Successful – Award
of 180-Day Exclusivity Period
Awarded to first ANDA holder to file a complete
application with patent challenge
Protection from other generic competition – blocks
approval of subsequent ANDAs
Protection triggered by:
First commercial marketing
Forfeiture provisions
36

37. Orphan Drug Exclusivity (ODE)
Orphan drug refers to a product that treats a rare disease -
affecting fewer than 200,000 Americans
7 years exclusivity
 Granted on approval of designated orphan drug
 OGD works with the Office of Orphan Products
37

38. COMPARISION
NDA ANDA
Applicable for new drug Applicable for generic drug
Take longer time ( 12-15
years)
Compare to NAD 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 38

39. HATCH WAXMAN ACT
 Also known as “The Drug Price Competition and Patent
Term Restoration Act”
 Enacted in 1984
-amended the Patent laws
-amended the Federal Food, Drug and Cosmetics Act.
 Before 1962 – new drug approved based on safety only.
 1962-proof of efficacy made compulsory for marketing
approval of a new drug (Kefauver -Harris Amendments)

40.  There was no provision for patent term extension prior
to the Hatch Waxman Act , to make up for the time
lost out of the total patent term during the marketing
approval process.
 Generic companies required to submit their own
comprehensive NDA
-costly
- time consuming
 If drug was covered by patent
-testing should not begin until patent expired
 To overcome the above problems an act was needed to
promote generic companies.

41. Types of Patent Certifications.
 When an applicant submits an ANDA to the FDA, the
applicant must certify one of the four things under
section 505(j)(2)(A)(viii):

42. WAXMAN HATCH AMENMENTS BENIFITS
TO INOVATOR’S COMPANIES TO GENERIC DRUG COMPANIES
IF SUIT
180 DAY EXCLUSIVITY PERIOD
TO CHALLEGE PATENT DRUG
45 DAY TO CLAIM
DELAYED FOR 30 MONTHS
NOT SUIT

43. PARA IV- Patent Challenge

44. 180 Day Market exclusivity
Awarded to first ANDA holder to file a complete
application with patent challenge.
Protection from other generic completion – blocks
approval of subsequent ANDAs.
Protection triggered by;
-first commercial marketing.
-forfeiture provisions.
 May be shared by multiple applicants.

45. 30-month stay of FDA approval
If infringement lawsuit can start prior to ANDA
approval and marketing=big gain for generics.
If patent owner or NDA holder sues the ANDA
applicant for patent infringement within 45 days of
receiving notice of the para IV certification.
Runs from date of notification or expiration of NCE
exclusivity.
May be lengthened or shortened by the court.

46. RECALL
 A recall is when a product is removed from the market or
a correction is made to the product because it is either
defective or potentially harmful.
 Sometimes a company discovers a problem and recalls a
product on its own. Other times a company recalls a
product after FDA raises concerns.
 If you have a medicine or device that has been recalled,
talk to your health care professional about the best
course of action. For other products, such as foods,
dietary supplements, and cosmetics, take them back to
the place of purchase and ask for a refund. Stores
generally have a return and refund policy when a
company has announced a recall of its products.

47.  Class I recall: a situation in which there is a reasonable
probability that the use of or exposure to a violative
product will cause serious adverse health consequences or
death.
 Class II recall: a situation in which use of or exposure to a
violative product may cause temporary or medically
reversible adverse health consequences or where the
probability of serious adverse health consequences is
remote.
 Class III recall: a situation in which use of or exposure to a
violative product is not likely to cause adverse health
consequences.

48.  Market withdrawal: occurs when a product has a
minor violation that would not be subject to FDA legal
action. The firm removes the product from the market
or corrects the violation. For example, a product
removed from the market due to tampering, without
evidence of manufacturing or distribution problems,
would be a market withdrawal.
 Medical device safety alert: issued in situations
where a medical device may present an unreasonable
risk of substantial harm. In some case, these situations
also are considered recalls.

49. Example for RECALL
Date Brand name Product
description
Reason /
problem
Company
name
06/29/2017 Ultra-Sten, D-
Zine
Marketed as a
dietary
supplement
Presence of
anabolic
steroids
Hardcore
Formulations

50. ALERT;
 The purpose of the New Drug Application (NDA) / ANDA Field
Alert Program is to quickly identify drug products that pose
potential safety threats.
 All drug manufacturers with approved New Drug Applications
(NDAs) and Abbreviated New Drug Applications (ANDAs) are
required to submit Field Alert Reports to the FDA if they find
any significant problems with an approved drug. Reports must
be submitted to district FDA offices within three days of a
problem being identified.

51.  Information that must be reported in a Field Alert Report
includes:
 any incident that causes the drug product or its labeling to be
mistaken for or applied to another article,
 bacterial contamination,
 a significant chemical, physical, or other change,
 deterioration in the distributed drug product, and
 failure of one or more distributed batches of the drug product
to meet the specifications established in its application.

52. WARNING LETTER
USFDA defines Warning Letter as,
“- a correspondence that notifies regulated industry
about violations that FDA has documented during its
inspections or investigations. Typically, a warning letter
notifies a responsible individual or firm that the Agency
considers one or more products, practices, processes, or
other activities to be in violation of the F.D&C Act, its
implementing regulations and other federal statutes.
Warning letter should only be issued for violations of
regulatory significances, i.e., those that may actually lead
to an enforcement action if the documented violations
are not promptly and adequately corrected. A Warning
Letter is one of the Agency’s principle means of
achieving prompt voluntary compliance with the Act’’

53. Why you’ve received an FDA Warning letter?
 Documents a violation of law or regulation.
 Establishes that a firm or person has been notified of
the violation.
 Your response to the FDA 483 may have been deficient.
 Designed to promote voluntary compliance.
 Stepping stone to regulatory action.

54. What does this letter mean for you & your firm?
 Warning letter is considered to be “prior notice”.
 Respond within 15 days.
 FDA will initiate necessary action if no response is
received .
 Time is CRITICAL-you have to organize, understand ,
resolve and respond to the FDA.

58. What does FDA inspect?
 FDA inspects manufacturers or processors of FDA-
regulated products to verify that they comply with
relevant regulations. Those inspected include
 vaccine and drug manufacturers
 blood banks
 food processing facilities
 dairy farms
 animal feed processors
 compounding pharmacies

59. FDA also inspects
 facilities that conduct studies in people (clinical trials)
 laboratories that conduct studies in animals or
microorganisms when these studies are used to apply for
FDA approval of a medical product
 foreign manufacturing and processing sites for FDA-
regulated products that are sold in the United States
 imported regulated products at the border
FDA conducts several types of inspections to help
protect consumers from unsafe products:
 pre-approval inspection after a company submits an
application to FDA to market a new product
 routine inspection of a regulated facility
 “for-cause” inspection to investigate a specific problem
that has come to FDA’s attention

62. Challenges faced by FDA.
 the rapid transformation of the science and
technology that generates the products FDA must
regulate;
 increasing expectations of consumers with changing
demographics and consumption habits to easily obtain
medical and risk-related information;
 the expanding and evolving composition of global
trade and production; and,
 emerging public health threats.

63. LAWS ENFORCED BY FDA
 Federal Food, Drug and Cosmetic Act
 Food and Drug Administration Modernization Act
 Infant Formula Act of 1980
 Orphan Drug Act
 Drug Price Competition &Patent Term Restoration Act
 Medical Device Amendments of 1992
 Prescription Drug User Fee Act of 1992
 Animal Medicinal Drug Use Clarification Act of 1994
 Dietary Supplement Health and Education Act of 1994
 Food and Drug Administration Modernization Act of
1997
 Best Pharmaceuticals for Children Act

64.  Medical Device User Fee and Modernization Act of 2002
 Animal Drug User Fee Act of 2003
 Minor Use and Minor Species Animal Health Act of 2004
 Food Allergen Labeling and Consumer Protection Act of
2004
 Federal Anti-Tampering Act
 Sanitary Food Transportation Act
 Mammography Quality Standards Act (MQSA)
 Bioterrorism Act of 2002
 Public Health Service Act
 Trademark Act of 1946
 Controlled Substances Import and Export Act

65. FDA in India
 FDA opened the India Office in New Delhi in 2008, to
ensure that food and medical products exported from
India to the U.S. are safe, are of good quality, and are
effective.
 FDA’s goals in India are to obtain information to help
make better regulatory decisions about the products
from India that are being developed and exported for the
U.S. market. This includes medical products being
reviewed for marketing authorization in the U.S., and
the safety assessment of products that are already on the
U.S. market. In addition, the India Office helps verify
that foods being imported into the U.S. are safe.

66. FDA activities in India include:
 Conducting inspections of medical products and foods
facilities that export to the U.S.
 Engaging with Indian regulatory authorities to build
confidence in each other and develop quality standards
 Partnering with Indian counterpart agencies on bilateral
initiatives
 Assisting and training Indian regulators, Indian
pharmaceutical and foods industries and stakeholders on
developing and maintaining the quality, safety and
effectiveness of medical products and foods
 Building and strengthening relationships with the
Government of India by supporting the mission of the U.S.
Embassy

67. HOW
TO
CONTACT
FDA?
Email: Contact FDA
Centers and Offices
Call:
1-888-INFO-FDA
(1-888-463-6332)
Write to:
Food and Drug Administration
10903 New Hampshire Ave
Silver Spring, MD 20993-0002

68. References:
 www.fda.gov
 Slideshare – swati singh

69. THANK YOU