DEVELOPMENT OF COMPLEX GENERIC PRODUCT FOR HIGHLY

REGULATED MARKETS

January 2018

5 NDA Vs. ANDA

9 Successful Commercial Launch

2

CONTENT OVERVIEW

7 Paragraph IV

8 Flow Chart for Pharmaceutical Development

6 Patent fight for ANDA

1 GENERIC BASICS & COST ADVANTAGE

2 What are Generics products?

3 Cost Saving & Price Reduction

4 Patent Exposure

GENERIC BASICS & COST ADVANTAGE

3

WHAT ARE GENERIC PRODUCTS 4

PHARMACEUTICAL EQUIVALENCE 5

COST SAVING AND PRICE REDUCTION 6

PATENT EXPIRY EXPOSURE 7

VALUE OF EXPIRING PATENTS 2019 8

MARKET SHARE TOP 10 GENERIC CORPORATIONS 9

NDA vs ANDA 10

▪ NDA is submitted based on FD&C Act 505(b).

▪ NDAs are submitted for:

▪ New molecular entity

▪ New formulation of previously approved drug

▪ New combination of two or more drugs

▪ New indication (claim) for already marketed drug

ANDA is submitted based on FD&C Act 505(j).

ANDAs are submitted for:

Generic drugs; a NDA must be previously approved and

listed, known as the reference listed drug (RLD)

Note: ANDA may not be submitted for five years after the

date of the approval of the New Molecular Entity (NME).

REQUIREMENTS FOR GENERIC DRUG 11

PATENT FOR NDA VS. ANDA 12

NDA

Patent information is required to be submitted with all new drug

applications at the time of submission of the NDA.

FDA relies on the NDA applicant or patent owner’s signed declaration

stating that the patent covers an approved drug product’s formulation,

composition or use.

ANDA

A certification for each patent listed in the “Orange Book” for the RLD must

state one of the following:

(I) No Patent Filed

(II) Patent Has Expired

(III) Patent Will Expire

(IV) Patent Challenge

PATENT AND EXCLUSIVITY 13

Patents are granted by the Patent and Trademark Office anywhere

along the development lifeline of a drug and can encompass a wide

range of claims.

Patents expire 20 years from the date of filing. Many other factors

can affect the duration of a patent.

Exclusivity is exclusive marketing rights granted by the FDA upon

approval of a drug and can run concurrently with a patent or not.

Orphan Drug (ODE) - 7 years

New Chemical (NCE) - 5 years

Pediatric Exclusivity (PED) - 6 months added

"Other" Exclusivity - 3 years for a "change" if criteria are met

Patent Challenge (PC) - 180 days (this exclusivity is for ANDAs

only)

PARAGRAPH IV CERTIFICATION & NON INFRINGMENT

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Orange Book Listings by NDA Holder

Abbreviated New Drug Applications (ANDA)

Patent Certifications by ANDA Applicants

Especially Paragraph IV Certifications

Notice Letter to Patent Owner

45-Days for Patent Owner to Sue

30-Month Stay of FDA Approval of ANDA

180-Day Marketing Exclusivity for Successful First-Filer –

delayed FDA approval of 2d ANDAs

DMF 15

Drug Substance Information

Most generic drug product manufacturers rely on

third parties for supplying drug substances.

Drug substance suppliers submit Drug Master File

(DMF) to FDA that may be used to provide confidential

detailed information about facilities, processes, or

articles used in the manufacturing, processing,

packaging, and storing of one or more human drugs.

Drug Master File

Type I: Facilities

Type II: Drug Substance

Type III: Containers & Closures (Bottles, Caps,

Syringes, Stoppers, etc.)

Type IV: Colors, Flavors

Type V: Excipients or Microbiology

DMF Review

DMFs are neither approved nor disapproved.

A DMF is reviewed to determine whether it is

adequate to support the particular Application that

references it.

THE ORANGE BOOK16

Approved Drug Products with Therapeutic Equivalence Evaluations

Contains list of all FDA approved drug products (NDAs, ANDAs and

OTCs)

Therapeutic equivalence codes

“A” = Substitutable

“B” = NOT substitutable

Patent and exclusivity expiration dates

Reference Listed Drugs - A drug product identified by FDA for

generic companies to compare their proposed products

POST-APPROVAL SUBMISSIONS 17

Supplement must be submitted for any change in the

drug substance, drug product, production process, quality

controls, equipment, or facilities. Prior Approval Supplement (PAS) – major changes

Changes Being Effected (CBE) – moderate changes

Annual report must be submitted each year within 60

days of the anniversary date of approval of the

application. May include some minor changes

PATENT TERM AND EXCLUSIVITY 18

Patent term extension - up to five years to compensate a

patent owner for the marketing time allegedly lost in the FDA

drug approval process.

Total patent term extension of up to 14 years.

NDA holder has Data Exclusivity for five years after date of

FDA approval of a New Chemical Entity (NCE)

NDA holder has Data Exclusivity for three years after date of

FDA approval of a new use of an existing and previously

approved chemical entity, or new dosage form using that

chemical entity.

BE REQUIREMENT 19

BE REQUIREMENT 20

▪ AUC and Cmax

▪ 90% Confidence Intervals (CI) must fit between 80%-125%

– Test (T) is not significantly less than reference

– Reference (R) is not significantly less than test

– Significant difference is 20% ( = 0.05 significance level)

– T/R = 80/100 = 80%

– R/T = 80% (all data expressed as T/R so this becomes 100/80 = 125%)

NON INFRINGEMENT ANALYSIS 21

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FLOW CHART OF PHARMACEUTICAL DEVELOPMENT

Project feasibility

Step 1Kick-off meeting

Step 2Formulation & process development

Step 3

Pilot BE study

Step 4Submission/

validation batch manufacturing

Step 5Pivotal BE study

Step 6

Dossier filling

Step 7

Post dossier filling

Step 8

Commercial launch

Step 9

KNOWLEDGE TRANSFER TO COMMERCIAL TEAM 23

▪ Knowledge transfer PPT

▪ Support for CF batches at commercial scale

▪ Support for commercial PV batches

▪ SUCCESSFUL COMMERCIAL LAUNCH OF THE PRODUCT

R&D scale up team to transfer product knowledge

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▪Thank You