The document provides a comprehensive overview of generic product development, detailing processes related to the formulation, analytical development, and regulatory requirements of generic drugs. It emphasizes the necessity for Abbreviated New Drug Applications (ANDAs) to demonstrate bioequivalence to reference drugs without duplicating extensive preclinical and clinical studies. Additionally, the document outlines the various stages of drug development, from literature searches to stability studies, highlighting the collaboration required across different departments.

1. Generic product development
Global prospective
Guru Balaji.S
Product development
India
Sep 22, 2018

2. Drug | API | DS : (Active pharmaceutical ingredients | Drug substance )
Substance that is intended to modify physiological states for the benefit of the recipient
Dosage forms : Mixture of drug components and nondrug components(excipients)
ANDA : Abbreviated new drug application
CTD : Common technical document
Dossier : A collection of documents about a particular person, event, or subject
Key words

3. Generic product :
It should be 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.
Generic drug sponsors do not have to duplicate the non clinical animal toxicity
studies nor expensive clinical efficacy and safety studies
Generics

4. API
Manufacturing
process
Excipients
Delivery form
Quality
Safety
Efficacy

5. Global regulatory agencies

6. Departments:
1. Formulation (FD)
2. Analytical (AD)
3. Packaging
4. Regulatory (RA)
5. Intellectual rights (IP
6. Development quality
assurance (DQA)
7. Production
8. Quality control (QC)
9. Quality assurance (Q
10.Warehouse
Generic
product
development

7. CTD Module : 1
Regional & Administrative
document
Module : 2
Overall summary
Module : 3
Quality
Module : 4
Safety
Module : 5
Clinical study reports
1
2
3
4
5

8. • ANDA termed “Abbreviated” because they generally need not
include preclinical & clinical data to establish safety & effectiveness.
• ANDA must scientifically demonstrate that their product is
bioequivalent to the innovator drug.
• An ANDA generally requires a BE study between the generic drug product and
Reference list of drugs(RLD )product.
• The safety and efficacy of the RLD product were established previously
through animal ,clinical ,BA studies.SO, no need to repeat for ANDA.
ANDA

9. The “orange book”
• The “Orange book” is the nickname for the
FDA’s “Approved Drug Products List with
Therapeutic Equivalence Evaluations”
• First published in 1979
• In 1984, FDA started adding patents to the
“Orange book” to keep track of which drugs
are covered by patents

10. Patents
No patents listed
Patents expired
Patent is there and will expire on
particular date
1
2
3
Generic applicant challenge the
innovator
4

11. Product development
Literature
search
API, RLD,
Excipients
procurement
Preformulation
study
Formulation &
Analytical
development
GenericsStability
studies
Validation

12. Stage 1: Literature search
 Compendiums:

13. Stage 1: Literature search
 On‐line computerized search:
Electronic data base
Articles, publication on test methods, Dissolution, synthesis
procedures, drug impurities, pharmacokinetics and dynamics etc.
Drugs@FDA: FDA Approved Drug Products
FDA Site:
FOI‐SBoA
FDA CDER: Evaluation of Biostudy parameters, dissolution methods.
Patent evaluation: Orange book
 Orange Book:
Approved Drug Products with Therapeutic Equivalence Evaluations

14. Stage 2 : Active Sourcing
 Identify potential suppliers
• DMF source
• Reliability
• Statement of non‐patent infringement
• Commitment for physical & chemical specifications
 Evaluate at least two suppliers fully
 Ask for
samples
CoAs and
Specifications
Open part of DMF

15. Stage 3 :Active Testing
 Physical characterization
• Polymorphism
• Particle size distribution
• Bulk density
• Microscopic observation etc.
 Chemical characterization
• Pharmacopoeia monograph (if present)
• Pharmacopoeia Forum (if available)
• In‐house method (based on manufacturer)
• Supplier's test methods and specifications
• Assay
• Stressed Analysis
• Degradants (Expected)
• Impurity profile
• Optical rotation
• Enantiomeric purity
• O.V.I. Testing

16. Stage 4 : Preformulation studies
 Application of biopharmaceutical principles to the physicochemical parameters
of a drug with the goal of designing an optimum drug delivery system.
 Characterization of drug molecule is a very important step
special studies are conducted depending on the type of dosage forms and drug
molecule nature
 Solubility determination
 pH and pKa determination
 Partition coefficient
 Solid state properties ( polymorphism)
 Powder flow properties
 Stability studies
 Moisture pick up studies

17. Stage 5 :Innovator | RLD
• Purchase at least 3 different lots
• smallest and largest pack size
Stage 6 :Innovator's product testing
 Physical and chemical parameters evaluation
 Packs evaluation
• containers materials
• closure types: CRC
• Fillers: cotton, Rayon etc.
• Desiccants: Silica gel, Molecular sieve etc.
• Labeling,
• PIL etc.

18. Stage 7 : Container Closure System/
Packaging development
Evaluation of suitable container‐closure system
 Choice of container‐closure‐liner system including:
• material composition,
• type of thermoplastic resin and resin pigments,
• manufacturers and suppliers,
• liners and seals used by closure manufacturer,
• cotton and desiccants.
• manufacturer's DMF numbers for all component parts
• Trade dress comparison with Innovator’s product

19. Stage 8 :Prototype formulations
development.
• Evaluations of suitable mfg. process
• Selection/ quantification of excipients
• Determination of order of mixing
• Determination of process parameters
• Hold time studies of product intermediates
Stage 9 :Formula Optimization
• Ratio of intra‐granulate Disintegrant and binders agents

20. Stage 10 :Analytical evaluations
Discriminatory dissolution profile method development
• Different types / Rate/ Media
• API and excipient specification
• Process development

21. Stability studies
• Stability of Innovator’s product and development batches
• Bio studies
• Process evaluation execution and batch summary report
• Exhibit batch execution and summary report
• Physical, chemical, biological, and microbiological
• Preservative content ( eg. Antioxidant, antimicrobials)
• Functionality test (eg. Dissolution rate for a dosage delivery system)
• Photostability testing on at least one primary batch of the drug product
(ICH Q1B)
Stability studies Duration
40°C±2°C and 75% RH ±5% RH (accelerated condition) 6 months
30°C±2°C and 65% RH ±5% RH (Intermediate condition) 6 months
25°C±2°C and 60% RH ±5% RH (Long term condition) 12 months

22. --------------------------- International Marketing / CEO
---------------------------- Formulation-R&D Team
---------------------------- Formulation-R&D / Commercial
----------------------------- Analytical -R&D
----------------------------- Formulation-R&D
--------- CRD/ARD
------------------------------ Formulation –R&D
Sourcing
API
Excipients
Innovator Product
Literature & patent search
Testing and Evaluation of
API
Excipients
Innovators Product
Preformulation study
Formulation development
Method development
New Product development (NPD)
Strategy for ANDA product development & filing
Responsibility

23. ----------------------------- Packaging Development
----------------------------- F-R&D / Stability Group
----------------------------- Clinical Pharmacology Dept.
------------------------------ CRD-Validation Team / A-R&D
---------------------------- F-R&D / Process Deployment Lab / Quality Assurance / Production
----------------------------- Quality Assurance / Quality Control
------------------------------ F-R&D / Process Development Lab / QA / Production
----------------------------- Quality Assurance / Quality Control
----------------------------- Clinical Dept.
------------------------------ Regulatory Affairs / Corporate Quality Assurance / QA
Packaging Development
Pilot Bio
Analytical Validation
Preliminary Stability
Scale –up
Process Qualification
Pre-exhibit batches
Stability Study
Pivotal Batch (Exhibit Batch)
BA / BE study
(US / EU / CA / ROW)
Pre-submission audit
And
ANDA submission
Stability Study
Responsibility

24. Applicant drug sponsor
ANDA submission
Application review
Acceptable
&
complete
Refuse to file
letter issued
No
Chemistry &
micro review
Labelling
review BE review
Request for plant
inspection
Preapproval
results ok?
Chemistry &
micro review
ok?
Labelling
review
Ok?
BE review ?
Approval withheld until
results satisfactory
ANDA approved Not approval letter Bio deficiency letter
ANDA review process
Facility
inspection

26. Knowledge……
is proud that he has learnt so much
Wisdom…
Is humble that he knows no more
William cowper

27. Guru Balaji.S