GENERIC PRODUCT DEVELOPMENT

Dr. V. VENKATESWARLUSenior Director

Head, FR&D, Biostudies and Packaging

IPDO Innovation PlazaDr.Reddy’s Laboratories

Generic Product

• A generic product is essentially identical to the brand name (reference) drug product in terms of active ingredient(s), dosage form, route of administration, quality, safety, efficacy, performance characteristics and therapeutic indication.

• Hatch-Waxman Act- Drug Price Control and Patent Restoration Act 1984

Business potential of Generic products

• In 2002, about 47% of prescription drug products are generic versions while 53% innovator products

• Total cost of prescription drugs is 192 billion dollars. The cost of generic products was only 10% (19.2 b $) indicating cost ratio of 1:18.

• The generic products growth rate is 19% in 1984, 36% in 1994 and 50% in 2004

• Every year about 4 billion dollars business potential exists for next four years due to patents expiry

Selection of Product

• Current market sales of innovator product• Patent/ exclusivity time frame• Complexity in the development and time lines• Availability of API, equipment and expertise• Competitor intelligence• Budget required• Return on Investment• Therapeutic area of the product• Geographies

API availability

• In-house versus out source• Patent landscape for API• Cost competitiveness• Patent protection for the new process/

form/ impurity profile/ residual solvents/stability

Regulatory Strategy

• NCE-1• Para I, II, III &IV• FTF, launch on approval, LTF• 180 day exclusivity• Exclusivity for the innovator:

– Orphan drug- 7 years– NCE – 5 years– 505B2- 3 years– Pediatric – 6 months

• Out licensing/ partnership

Biostrategy

• Pilot BE studies• Pivotal BE studies: Fasting, Fed and

steady state studies; statistical design, volunteers, bioanalytes

PROJECT MANAGEMENT

• Defining the objectives of the project• Determining various tasks to be performed• Defining the time lines for each task• Determination of critical chain• Buffer management• Finalization of due date• Risk identification and mitigation plans• Budget and resource allocation

Steps involved in Generic Product Development

• Selection of drug product for development (BD)• API development (API R&D)/ sourcing (SCM)• Analytical method development and validation

for API and prototype formulation- In vitro methods establishment (AR&D)

• Literature search and patent landscape to identify possible excipients and processes (IPM)

• Regulatory strategy for ANDA filing (RA)– Para IV filing for 180 day exclusivity

• Pre-formulation and prototype formulations (FR&D)

Analytical method development and validation

• Analytical method development for API, formulation, dissolution and other tests

• Method validation for API and impurities (Process and degradation products)

Formulation Development Strategy

• Literature, patent landscape and innovator design

• Regulatory strategy and Biostrategy• Product development strategy• Preformulation and prototype formulation• Bench scale and lab scale studies• PE batch• Exhibit batches

Steps involved in Generic Product Development

• Bench scale – 1/100th of Exhibit batch– One month stability and reproducibility

• Lab Scale- 1/10th of Exhibit batch– One month stability in various packs and reproducibility

• Pilot BE studies (COE BIO, CPPK & Bioanalytical)• Process validation batch 1/4th to 100%

– Resolving process issues (PD)• Initiation of Exhibit batch

– Pilot BE clearance, Stability data clearance, analytical method transfer, procurement of excipients and specific equipment, In process quality control, specifications, BMR

– PDR (FR&D)

Steps involved in Generic Product Development

• Execution of exhibit batches– Stability loading in different packs (Packaging)

• Pivotal BE studies (COE BIO, CPPK & Bioanalytical)• ANDA preparation (RA)• Submission to FDA (RA)• Legal/ Regulatory Process (Legal and RA)• Approval• Commercial validation batches (FTO, QA & QC)• Commercial Batches and Launch (Marketing)

Approval Process in USFDA• Office of Generic Drugs (OGD) is responsible for

processing and approving ANDA• ANDA is reviewed for completeness before initiating

approval process• ANDA is reviewed under four sections

– Plant inspection report– Chemistry/microbiological– Labelling– Bioequivalence

• Tentative approval is given if time to launch the product is ahead of approval

• If patent litigation is in progress, the approval will be held for 30 months or judgment in favor of ANDA is given, which ever is earlier

• Approval to market is issued If no hurdles are present

APPROVAL PROCES IN EUROPE

• Obtaining MHRA slot for dossier submission

• Submission of dossier with all details• Review of dossier- time frame Day 70,

100, 105, 145• Stop clock

APPROVAL PROCESS IN INDIA

• Submission of application for M&M permission• Details required for approval

– API related details– CMC section

• Formulation composition, process, manufacturing controls, stability data

– BE report or BE and CT reports if first time in India

• DCGI and DCA routes

THANKS YOU

There is no substitution for sincerity and hard work