GENERIC DRUG DEVELOPMENT PROCESS AND HATCH WAXMAN ACT

1. GENERIC DRUG DEVELOPMENT PROCESS AND
HATCH WAXMAN ACT
Presented by
AYAN PAL
M.PHARM, 1st SEM
DEPARTMENT OF PHARMACEUTICS
CALCUTTA INSTITUTE OF PHARMACEUTICAL
TECHNOLOGY AND AHS

2. CONTENTS
 DEFINITION
 SELECTION OF GENERIC DRUG FOR MANUFACTURE
 GENERIC DRUG APPROVAL PROCESS
 STEPS IN GENERIC DEVELOPMENT PROCESS
 HATCH WAXMAN ACT AND AMENDMENTS
 OBJECTIVE AND SALIENT FEATURES OF THE ACT
 ORANGE BOOK
 REFERENCE

3. GENERIC DRUGS
DEFINITION:-A generic drug product is essentially identical to
the brand name(reference) drug product in terms of active
ingredient, dosage form ,route of administration, quality
,safety, efficacy, performance characteristics and therapeutic
indication.
 EX- PHENYTOIN is the generic drug and DILANTIN is the
brand name for the same drug.
 Brand drugs are the drugs which are protected by the
patent.
 In 2002 about 47%of prescription drug product are generic
versions while 53% innovator product.
 Every year about 4 billions dollars business potential exists
for next 4 years due to patent expiry.

4.  Current development and approval of generic drug products
was associated with issues concerning.
 Safety, efficacy and therapeutic equivalence of such products
early compared to the innovator or brand- name drug
product for obtaining marketing approval.
 However, the generic pharmaceutical industry is still
challenged by legislative, regulatory and scientific issues that
must be addressed to allow for the manufacture , approval
and marketing of generic drugs products.
 Generic drug product manufacturers must formulate a drug
product that will have the same therapeutic efficacy and
clinical performance as their brand-name counterpart.

5. SELECTION OF GENERIC DRUGS FOR MANUFACTURE
 The main driving force for the selection of generic drug
products for manufacture is the estimated sales volume for the
branded product.
 And the potential market share that the firm expects to have
once the generic drug product is manufactured and approved
for marketing.
 In addition to the expiration date of the patent for the active
ingredient, the generic firm must consider any other patent
claims and exclusivities that the innovator firm has filed.

6. The generic drug manufacturer needs to consider:
 The lead time that is needed to make the product and
submission of an Abbreviated New Drug Application (ANDA) to
the U.S.FDA for approval.
 Moreover, there is a financial incentive to being the first generic
drug product filed and approved by FDA.
 180-days exclusivity, is given under certain conditions, for the
generic manufacturer who is to file first.
Formulation considerations for generic drugs include:
 The availability of raw materials, chemical purity, polymorphic
form.
 Particle size of the active pharmaceutical ingredient.
 Any patents that the innovator company has filed, including
patents for the synthesis of the active pharmaceutical ingredient
and composition of the dosage form

7. GENERIC DRUG APPROVAL PROCESS
 The FDA’s office of Generic Drugs is responsible for reviewing the ANDA
and approving the drugs products marketing.
 The FDA’s Office of Generic drugs has a website http//www.fda.gov.org
that provides additional information for manufactures of generic drug
products that includes flow chart presentation of ANDA review process.
 And it also describes how FDA determines the quality, safety, and efficacy
of generic drug products prior to the approval for marketing.
 Generic drug application reviewers focus on bioequivalence data,
chemistry and manufacture quality ,microbiology data where relevant,
requests for plant inspection, and drug labeling information.
 FDA approved generic drugs must meet the same rigid standards as the
innovator drug.
 To obtain FDA approval, a generic drug product must- contain same active
ingredient as an approved drug product the inactive ingredients may vary.

8.  Be identical strength, dosage form ,route of administration, same
indications , bioequivalent, meet the batch requirements.
 The FDA’s Approved Drug Products with Therapeutic Equivalence
Evaluations and lists of the all approved products, both innovator and
generic are included in the orange book

9. STEPS IN GENERIC DRUG PRODUCT DEVELOPMENT PROCESS
 CONCEPT DEVELOPMENT
 SYSTEM LEVEL DEVELOPMENT
 DETAIL DESIGN
 TESTING AND REFINEMENT
 PRODUCTION RAMP UP

10. HATCH WAXMAN ACT AND AMENDMENTS
 The "Drug Price Competition and Patent Term Restoration Act of 1984,"
also known as the Hatch-Waxman Amendments, established the approval
pathway for generic drug products, under which applicants can submit an
abbreviated new drug application (ANDA) under section 505(j) of the
Federal Food, Drug, and Cosmetic Act (FD&C Act).
 In 1984 United States Federal law which encourages the manufacture of
generic drugs by the pharmaceutical industry and established the modern
system of government generic drug regulation in the United States.
 In order to overcome the above problem an act was needed to promote
generic drug and innovators.
 In 1984, Two American politicians Orrin Grant Hatch & Henry Arnold
Waxman sponsored the Official act “ The Drug Price Competition and
Patent Term Restoration” since then this Act was informally known as
Hatch-Waxman Act.

11. OBJECTIVES OF THE ACT
 Reduce the cost associated with approval of generic drugs.
 Allowing the early experimental use.
 Compensating the branded drugs manufactures for the time lost from
the patent term because of the regulatory approval formality.
 Motivating the generic drug manufactures.

12. SALIENT FEATURES OF THE ACT
 Patent term extension.
 Patent challenges.
 Exemption to infringement.
 Generic exclusivity.
 Prior to the generic drug manufacturer had to do the entire clinical trials.
 After the passage of this act the generic drug manufacturer had to prove
bioequivalence of generic drug to innovator drug.

13. PROVISION OF THE ACT
 Creation of section 505(j).
 Selection 505(j) established the ANDA approval process.
 The timing of an ANDA approval depends in part on patent protection for
the innovator drug.
 NDA must include any patent that claims the drug or a method of using
the drug for which a claim of patent infringement could reasonably be
asserted.
 On approval of NDA, FDA publishes patent information of drug in orange
book.
 An NDA applicant must submit the following information for each patent
– a) Patent no and date on which the patent will expire. b) Type of patent,
drug product, method of use, name of the patent owner must be specified.

14. TYPES TERMS
NEW CHEMICAL ENTITY 5 YEARS
NEW CLINICAL ENTITY 3 YEARS
ORPHAN DRUG 7 YEARS
PEDIATRIC EXCLUSIVITY 6 MONTHS
180 DAYS GENERIC MARKET
EXCLUSIVITY
180 DAYS

15. FOUR TYPE OF PATENT CERTIFICATIONS
When an applicant submits an ANDA to the FDA, the applicant must
certify one of four things under section 505(j)A(vii)
A)That the required patent information relating to such patent has not
been filed
B) That such patent has expired
C) That the patent will expire on a particular date
D) That such a patent is valid or will not be infringed by the drug, for
which approval is begin sought patent challenge

16. ORANGE BOOK
 On approval of NDA, FDA publishes patent information of drug are
included in orange book.
OBJECTIVE
 This book contains therapeutics equivalence evaluations for approved
prescription drug products.
 These evaluations are been prepared to serve as public information.
 To advice to state health agencies, prescribers, pharmacists to promote
public education in area of drug product selection.
 To review to patterns of access and usage.
 To allow discovery of use of unusual privileges.
 To allow discovery of repeated attempts to bypass protections.
 To supply an additional form of user assurance.

17. CONTENTS OF THE ORANGE BOOK
 Introduction
 Content and exclusion
 Reference listed drug
 General policies and legal status
 Drug product list :-
A) Prescription drug product list
B) OTC drug product list
 The orange book is composed of 4 parts:
1)Approved prescription drug products with the therapeutic equivalence
evaluations
2)Approved OTC drugs products
3) Drug products with approval under section 505 of the FDC act
4) A cumulative list of approved drug products that have never been
marketed.

18. REFERENCE
 IPR AND DRUG REGULATORY AFFAIRS by DR GAURAV TIWARI
(NIRALI PRAKASHAN)
 DRUG REGULATORY AFFAIRS by SACHIN ITKAR (Nirali prakashan)
 http//jddonline.info>article>view
 Generic drug product development solid dosage form by Marcel
Dekker.
 Biopharmaceutics and pharmacokinetics by DM Brahmankar

19. THANK YOU