introduction to genric drug

7/30/2019 Introduction to Genric Drug

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Introduction To Generic Drug

S.Ganesan

IPR Dept. , R&D

Orchid Chemicals and Pharmaceuticals

4th September 2004


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OBJ ECTIVES

To provide basic idea about the generic drugs , theirapproval and Marketing in US.

Introduction to Hatch-Waxman Act and its role indeveloping US generic market

Strategies used to delays generic drug entry by BrandCompany

Determining the expiry of US patents

Patent term extensions under 35USC 156


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What is a generic drug

Same active ingredient(s)

Same route of administration

Same dosage form

Same strength

Same conditions of use

Compared to reference listed drug (RLD) -(brand name product) in orange Book


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U.S. Pharmaceutical Sales in $.

.

$57.5$61.7

$68.4$77.9

$87.9

$101.7

$121.7

$138.5

$0

$25

$50

$75

$100

$125

$150

1993 1994 1995 1996 1997 1998 1999 2000

Source: IMS Health

$

in

Billions


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Value of Generics:

Real Business is yet to come...

$7

$41

$0

$10

$20

$30

$40

$50

Off-Patent w/oCompetition

Losing PatentProtection by 2010

$ in Billions


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Hatch-Waxman Act

The Drug Price Competition and Patent Term

Restoration Act of 1984

Its a dual balancing act


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Hatch-Waxman Act

Benefits to Innovator:

Patent term extension

Exclusivity provision

Benefits to Generic :

Abbreviated New Drug Application (ANDA)

bioequivalence

no clinical testing

Patent challenges and generic exclusivity

Exemption to infringement


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NDA vs ANDA.

1. Chemistry

2. Manufacturing

3. Controls4. Labeling

5. Testing

6. Animal studies

7. Clinical studies

8. Bioavailability

Chemistry

Manufacturing

ControlsLabeling

Testing

Bioequivalence

NDA ANDA


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Cost of Drug Innovation Vs

Imitation

Innovation Long Gestation Period --- 10 yrs (approx)

Low Success Rate

High R&D cost ~ 800 mn$/NCE

Imitation

Short Gestation Period -- 1.5 to 2 Yrs

Low R&D cost ~1-2 mn$


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Patent Term Extension

(PTE)

Provides (limited) patent term restoration to

innovators to compensate for delay in FDA

approval process

One PTE per drug

One PTE per patent

Extension may not be more than 5 years

Total term (as extended) may not exceed 14years from approval


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Patent Must Claim:Product

Drug Product

= Active Ingredient

Biologic, medical device, food and color additives

Method of using product


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Basic Conditions:

Term of patent not expired

Patent never extended

Product subject to review before commercialmarketing or use

Application submitted by owner or agent

First permitted marketing of product


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Term of Extension:

1/2 x [(Begin: IND Effective)(End:Initial NDA Submission)]

+(Begin: Initial NDA Submission)

(End: Date of Approval)

Reduce if applicant did not act with due diligence To sum up;

Formula = 50% development time + 100%review time (less any non-diligent time) up to 5years


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HOECHST-ROUSSEL Vs LEHMAN

4,631,286 claims 1-hydroxy-tacrine and its use

Requested extension on the basis of Tacrine

Approval Rejected by USPTO

N

N

PTE-Tacrine

Extension is given to Innovator (Warner-Lambert)

Method of use patent.


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Cefdinir Omnicef Tablet


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Cefdinir Omnicef Oral Suspension


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Adjustments in patent term

extension..

1. The PTOs delay

(examining or processing an application)

2. interferences, and

3. Application pending for more than 3 years.


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Orange Book

Title of the Orange Book: Approved drug productswith therapeutic equivalence evaluations

Electronic Version: http://www.fda.gov/cder/ob/

All FDA approved drug products listed (NDAs, OTCsand ANDAs)

Expiration dates: patent and exclusivity

Reference Listed Drugs/ brand drugs identified by

FDA for generic companies to compare with theirproposed products

FDAs Position: Administrative Function Only

Lists Patents that are Granted


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Exclusivity & Patent Listings

NDAmust notify about patents that claim thedrug product that is the subject of the NDA.

Patents that are notified by originators in NDAsare listed by the FDA in the publication

Approved drug products with therapeuticequivalence evaluations Commonly recognizedas the Orange Book.

Patent listings

30 days of new approval30 days of issuance if drug already approved

Lists all current exclusivities and submittedpatents


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Creation of ANDA

Patent Certifications I no patent information filed in OB I I filed patent has expired

I I I will await patent expire IVwont infringe or patent invalid requires notice

to patent holder with detailed statement of law andfact for why patent should not block ANDA


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Paragraph II

Mesalamine (ENEMA; RECTAL )


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Zaleplon

4,626,538 06.06.2008 (1,810 days)

PARA III


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Amlodipine

Para IV or III

R i lit M l t


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Rosiglitazone Maleate

Para IV or III

PARA IV

St t t E l i iti U d


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Statutory Exclusivities UnderHatch- Waxman..

Exclusivity is marketing protection

Exclusivity is given & enforced by FDA

Exclusivity prevents the marketing of anidentical generic or 505(b)(2) product for a

certain period of time

Exclusivity prevents either the submission or

approval of an ANDA application


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New Chemical Entity (NCE) Exclusivity

Granted to a drug that contains no active moiety that

has been approved by FDA in any other [NDA]. Five year exclusivity

NCE exclusivity runs from time of NDA approval and

bars FDA from accepting for review any ANDA or

505(b)(2) application for a drug containing the sameactive ingredient for.

five years if ANDA or 505(b)(2) does not

contain a paragraph IV certification to a

listed patent four years if ANDA or 505(b)(2) contains

a paragraph IV certification to a listed

patent

Fondaparinux Sodium


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Fondaparinux Sodium

Patent expired on August 19, 2003

NCE market exclusivity expiresDecember 7, 2006


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3-Year Exclusivity

Available for NDAs which contain: Reports of "new" "clinical trials"

That were "essential to approval" of theNDA

Conducted or sponsored by the applicant

FDA may not approvean ANDA or 505(b)(2)NDA for 3 years after approval

Applies for new indications, Rx OTCswitch (Omeprazole ), new dosing regimen,and some other labeling changes, New esters,etc


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Omeprazole Rx-OTC Switch

NP (01.03.2007)

Lansoprazole (INJECTABLE; INTRAVENOUS )

NDF: 27.05.2007


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Orphan Drug Exclusivity

Granted to drugs designated and approved to treat

diseases or conditions affecting fewer than 200,000 inthe U.S. (or more than 200,0000 and no hope ofrecovering costs)

Seven year exclusivity

Orphan exclusivity bars FDA from approving any otherapplication (ANDA, 505(b)(2) or full NDA or BLA) forthe same drug for the same orphan disease or conditionfor seven years.

Eg ; Zoledronic AcidProduct Patent Expiry : 24.07.2007

NCE Expiry : 20.08.2006

ODE Expiry : 20.08.2008

Anagrelide Hydrochloride


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AnagrelideHydrochloride

Patent US RE 31,617

Expiry; January 13, 1993

Approval date Mar 14, 1997 ODE until March 14, 2004

P di t i E l i it


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Pediatric Exclusivity

Pediatric exclusivity is an incentive developed

by Congress to encourage sponsors to conductpediatric studies

Six month exclusivity

Pediatric exclusivity does not stand alone - it

attaches only to existing exclusivity or patents

Possible delay of generic approval by six month

period

Sumatriptan Succinate


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Sumatriptan Succinate


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Patent Challenge Exclusivity

Granted to ANDA application containing

PARA-IV certification

Only to first filer

Moexipril


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Moexipril

First generic to file paragraph IV

certification

Listed Patent only one US 4,743,450 relatespharmaceutical composition

non-infringement of a US Patent by TEVA

180 day exclusivity


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505 (b) 2 Applications

Not a completely New Product

Not a me too Product

Approval requires clinical data

(Basic studies related to safety and Efficacy

can be taken from others)


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505(b)(2) applications

Like ANDAs

Blocked by exclusivity

Required to file patent certifications

Unlike all ANDAs

Able to earn exclusivity

May differ from RLD in more ways


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Patent Term Calculation

The Face of the Patent is not the Whole Story in

Determining Effective Patent Life in the US

Factors Affecting include:

GATT

Terminal Disclaimer

Patent Term Adjustment

Maintenance Fees

Interference

Invalidation


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Patent Term

GATT

US Patents filed prior to June 8, 1995 receive

the greater of 17 years from grant or 20 yearsfrom first filing.

After June 8, 1995, 20 years from first filing.


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Patent Term CalculationIllustrative example

US 5,856,336 expires

Date of Filing : May 25, 1992 FD

Date of Effective Filing : Aug.19, 1988 FFD

Date of Grant : J an. 5, 1999 GD

Date of Expiry : J an 5, 2016

Date of priority : Aug 3, 1988


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US 5,565,447 expires

Date of Filing : May 9, 1995

Date of Effective Filing : Mar 28, 1994

Date of Grant : Oct 15, 1996 Date of Expiry : Mar 28, 2014


But there is a Certificate of Correction for First filing


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US 5,565,447 expires Date of Filing : May 9, 1995

Date of Effective Filing : Mar 28, 1994 wrong date

J ul. 19, 1993

Date of Grant : Oct 15, 1996 Date of Expiry : Mar 28, 2014 wrong expiry

Oct 15, 2013


There is a Certificate of Correction for First filing


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Terminal Disclaimers

To Obviate a Provisional Double Patenting

Rejection

A Terminal Disclaimer can reduce thePatent term and will not increase the term of

patent.


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Maintenance Fees

Payment of maintenance fees is necessary to preventpatent expiration

Must be paid on or before due date or within six months

grace period.

Can be paid after grace period if unintentional (within 24months) or unavoidable (any time).

3 and , 7 and , 11 and month

P t t T C l l ti


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Patent term extension (PTE) is5 Year from actual Patent expiry

or

14 years from product approval by FDA

which ever is earlier


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How to know if innovator has applied for Patentterm extension (PTE)

Apply 14 year rule

Request for PTE has to be made within 60 daysfrom approval date.

Requested USPTO for the information on PTE

applications No information is available for some of the

products

Federal Register- Search

C f il


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Cefprozil

Product Patent : US 4,520,022Date Of Grant : 28.05.1985

First filing Date : 28.01. 1983

Before GATT Expiry : 28.05.2002

After GATT : 28.01.2003 Extensions Given : 1305 days

Date of Expiry : 25.08.2006

Date of Approval : 23.12.2001

Apply 14 year Rule

Corrected Expiry : 23.12.2005


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Medicare Reform Loopholes in Hatch Waxman Act

Multiple and Improper patent Listing

Brand Migration (Prilosec to Nexium)

Tie up with first Generic company

Cementing With Medicare Reform Only one 30 month Delay

Clarify patent submission and listing requirements

Generic drug entry

Drug TotalNumber

Total Length of Stays Net Sales inYear the Second


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Product of Stays Stay was Issued

Hytrin 3 70 months(The time from the beginning ofthe first stay until the end of the

final stay lasted approximately70 months, but the stays werenot overlapping)

Between $500and $750 million

Paxil 5 65 months Over $1 billion

Taxol 2 Potentially 60 months(The actual length of stays wereshorter because of courtactions)

Between $750million and $1billion

BuSpar 2 Potentially 30 months(The actual length of stays wereshorter because of courtactions)


Neurontincapsules

2 53 months Between $250million and $500million

Neurontintablets

2 37 months Between $250million and $500million

Tiazac 2 Potentially 60 months(The actual length of stays wereshorter because of courtactions)


2002 FTC Study at p. 49

T S U


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To Sum Up

Knowledge of IP is essential for all Generic Business is awaited

Know about when to enter.

Early entry will be benefited

Cost effective NIP is needed for Generic Drug

Consult IPM for any IP related matters


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THANKS

introduction to genric drug

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