This document discusses the process of generic drug product development. It explains that a generic drug is identical to the branded reference drug in terms of active ingredients, dosage form, safety and efficacy. The document then outlines several key steps in generic drug development, including selecting a product, ensuring API availability, developing analytical methods, conducting formulation development studies, manufacturing exhibit batches, conducting bioequivalence studies, and seeking regulatory approval from agencies like the FDA. It also discusses provisions of the Hatch-Waxman Act that aim to facilitate generic drug approval while compensating branded manufacturers.

1. GENERIC
PRODUCT
DEVELOPMEN
T
Dr.Prakash G
Department of
Pharmaceutics

3. 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.

4. 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

5. 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

6. 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

7. Steps involved in Generic
Product Development
 Selection of drug product for development
 API development (API R&D)/ sourcing
 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
 Regulatory strategy for ANDA filing (RA)
 Para IV filing for 180 day exclusivity
 Pre-formulation and prototype formulations (FR&D)

8. 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)

9. 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
 BE batch
 Exhibit batches

10. 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
 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

11. Steps involved in Generic Product
Development
Execution of exhibit batches
 Stability loading in different packs (Packaging)
Pivotal BE studies
ANDA preparation (RA)
Submission to FDA (RA)
Legal/ Regulatory Process (Legal and RA)
Approval
Commercial validation (QA & QC)
Commercial Batches and Launch (Marketing)

12. 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

13. 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

14. APPROVAL PROCESS IN INDIA
Submission of application
Details required for approval
 API related details
Formulation composition, process,
manufacturing controls, stability data
 BE report or BE and CT reports if first time in India
DCGI and DCA routes

15. Hatch Waxman Act
The act which surrounds the generic drug approval process
of the USFDA is the “Hatch Waxman Act of 1984” which
we also identify by the “Drug price control and Patent
Term Restoration Act of 1984” which led to a plethora of
generic drugs entering into the market.

16. Objectives of the act:
Reducing the cost associated with the approval of a
generic drug
Allowing Early-Experimental-Use
Compensating the branded drugs manufacturers for the
time lost from the patent term because of the regulatory
approval formality
Motivating the generic drug manufacturers

17. There was no provision for patent term extension prior to
enactment of 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 could not begin until patent expired
To overcome the above problems an act was needed to
promote generic companies

18. Provisions of the act
Creation of section 505(j)
Section 505(j) established the ANDA approval process
The timing of an ANDA approval depends in part on patent
protections 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 for
drug in Orange Book (“Approved Drug Products with
Therapeutic Equivalence Evaluations”)

19. An NDA applicant must submit the following information for each patent:
 Patent no and date on which the patent will expire.
 Type of patent i.e. drug, drug product or method of use.
 Name of patent owner.
 The name of an agent of the patent owner or applicant.

20.  Brand drugs listed for generics to compare with their proposed
products.
 Four Types of Patent Certifications
 When an applicant submits an ANDA to the FDA, the applicant must
certify one of four things under section 505(j)(2)(A)(vii):
I. That the drug has not been patented;
II. That the patent has already expired;
III. The date on which the patent will expire, and that the generic drug
will not go on the market until that date passes; and
IV. That the patent is not infringed or is invalid.
Those certifications are now referred to as the paragraphs I, II, III, and IV
certifications.

25. THANKYOU