Module 3 for pharmaceutical development

1. MODULE 3
Mr.Gunjan.Reddiwar

2. ICH consists of 6 sub topics
 Q1-Stability testing
 Q1A-Stability testing of new drug substances & products
 Q1B-Photo stability testing of new drug substances & products
 Q1C-Stability testing of new dosage form
 Q1D-Bracketing & matrixing designs for stability testing of new drug substances &
products
 Q1E-Evaluation of stability data
 Q1F-Stability data package for Registration Applications in climatic zones III & IV
 Q2-Analytical method validation
 Q3-Impurity testing
 Q4-Pharmacopoeial harmonization
 Q5-Quality of biotechnological products
 Q6-Specifications for new drug substances & products
 Q7-
 Q8- Pharmaceutical Development (Quality by Design)
 Q9-Quality Risk Management
 Q10- Pharmaceutical Quality Systems

3. 3.2.S DRUG SUBSTANCE (THIS ALL DOCUMENT WILL BE GIVEN BY VENDOR)
3.2.S.1- General information (name, manufacturer)
3.2.S.1.1-Nomenclature
3.2.S.1.2-Structure
3.2.S.1.3-general properties
3.2.S.2-Manufracture
3.2.S.2.1-manufractures
3.2.S.2.2-Description of mfg process & process control
3.2.S.2.3-Control of materials
3.2.S.2.4-control of critical steps & intermediates
3.2.S.2.5-Process validation/ evaluation
3.2.S.2.6-manufracturing process development
3.2.S.3-CHARATERIZATION
3.2.S.3.1-Elucidation of structure & other chareters
3.2.S.3.2-impurities

4. 3.2.S.4-CONTROL OF DRUG SUBSTANCE
3.2.S.4.1-Specification
3.2.S.4.2-Analytical procedure
3.2.S.4.3-Validation of analytical procedures
3.2.S.4.4-batch analysis
3.2.S.4.5-justification of specifications
3.2.S.5-REFERENCE STANDARD OR MATERIAL
3.2.S.6- CONTAINER & CLOSURE
3.2.S.7- STABILITY
3.2.S.7.1-Stability summary& conclusion
3.2.S.7.2-post approval stability protocol & commitment
3.2.S.7.3-stability data

5. 3.2.P-DRUG PRODUCT
3.2.P.1-DESCRIPRTION & COMPIOSITION OF DRUG PRODUCT
dossage form
Composition
Description of accompanying reconstitution of diluents(s)
Type of container and closure
3.2.P.2-PHARMACEUTICAL DEVELOPMENT
Dosage form
Formulation
Manufacturing process
Container closure system
Microbiological attributes
3.2.P.2.1-Components of drug product
3.2.P.2.1.1-Drug substance(physicochemical chareterisation)
Water content
solubility
paricle size distribution
polymorphic
solid state form

6. 3.2.P.2.1.2-EXCIPIENTS
Concentration
Chareteristics w.r.t. their function
3.2.P.2.2-DRUG PRODUCT
3.2.P.2.2.1-Formulation Development
Brief summary of drug product
Route of drug administration and usage
Different clinical formulation & formulation (i.e.)
Results of comparative in vitro studies or in-vivo studies
3.2.P.2.2.2- OVERAGES
3.2.P.2.2.3-PHYSIOCHEMICALO& BIOLOGIAL PROPERTIES.
Performance of drug product
pH
ionic strength
dissolution
redispersion
particle size distribution
aggregation
polymorphism
rheological properties
biological properties/activity/potency.
Immunological activity

7. 3.2.P.2.3-MANUFACTURING PROCESS DEVELOPMENT
Selection and optimisation of mfg. Process and critical steps involved
Relevant method of sterilization.
3.2.P.2.4-CONTAINER AND CLOSURE
For storage:
choice of material
protection from moisture and light
comparability of materials of construction with dosage form (sorption
to container and leaching )
safety of materials of construction
3.2.P.2.5-MICROBIOLOGICAL ATTRIBUTES
3.2.P.2.6-Compatibility
Compatibility of drug product with reconstitution diluents or dosage
devices
e.g. precipitation of drug substance in solution .

8. 3.2.P.3-MANUFRACTURE
3.2.P.3.1-MANUFRACTURER
Name , adress & responsibility of each mfg contractors & each
proposed production site
3.2.P.3.2 Batch formula
Batch formula should be provided
List of all components of dosage form
Amounts on a batch basis including overages & reference to quality
standard.
3.2.P.3.3.- DESCRIPTION OF MANUFRACTURING
PROCESS AND PROCESS CONTROL
Flow diagram should be presented giving the steps of the process and showing
where materials enter the process
The critical steps and points where process control, intermediate tests or final
product control are conducted should be identified.
Narrative description of mfg process including packaging that represents the
sequence of steps undertaken & sale of production provided
Novel process or technologies and packaging operations that directly affect
product quality
Equipment must be identifies type work capacity (e.g tumble blender, in line
homogenizer)
Steps should have appropriate process parameter identified (time temperature,
pH,
Environmental conditions (low humidity )

9. 3.2.P.3.4-CONTROL OF CRITICAL STEPS & INTERMEDIATES
Critical steps test & acceptance criteria should be provided.
e.g- justification, including experimental data
3.2.P.3.5- PROCESS VALIDATION AND EVALUATION
Description ,documentation& result of validation must be provided
for critical steps.
Critical assay of used in mfg process
e.g-validation of the sterilization process or aseptic filling
3.2.P.4-CONTROL OF EXCIPIENTS
3.2.P.4.1-SPECIFICATION
[Q6A &Q6B)
3.2.P.4.2-ANALYTICAL PROCEDURE
[Q2A & Q6B]

10. 3.2.P.4.3-VALIDATION OF ANALYTICAL PROCEDURES
Analytical validation information
Experimental data
Analytical procedure used for testing excipients
3.2.P.4.4-JUSTIFICATIONN OF SPECIFICATION
[Q3C&Q6B]
3.2.P.4.5-EXCIPIENTS OF HUMAN OR ANIMAL ORIGIN
Information provided regarding adventitious agent
Sources
Specification
Description of the testing performance
(viral safety data sheet)

11. 3.2.P.4.6-NOVEL EXCIPIENTS
For excipients used 1st time in drug
New route of administration
Full details of manufacturer
Characterization & control
Cross reference supporting safety data(non clinical or clinical data)
3.2.P.5-CONTROL OF DRUG PRODUCT
3.2.P.5.1-Specifications
Drug product (Q3B, Q6A,& Q6B)
3.2.P.5.2-Analytical procedure
Testing of drug product (Q2A and Q6B)
3.2.P.5.3-Validation of analytical procedures.
Validation information including
Experimental data [Q3B,Q3,Q6A&Q6B]
Analytical procedure

12. 3.2.P.5.4- Batch analysis
Description of batches and results showed be provided
3.2.P.5.5- Characterization of impurities
[Q3B,Q5C,Q6A&Q6B)
3.2.P.5.6- Justification of specifications
Drug product specifications [Q3B, Q6A&Q6B]
3.2.P.6-REFERENCE STANDARD OR MATERIALS
Information on the reference material used for testing of drug product.
3.2.P.7-CONTAINER AND CLOSURE
Description & identification
Non compound method(validation)
Non functional secondary packing compound
Brief description of secondary packaging component.

13. 3.2.P.8 STABILITY
3.2.P.8.1- Stability summary And conclusion
e.g. conclusion w.r.t storage condition and shelf life
[Q1A, Q1B, Q3B, Q5C&Q6A]
3.2.P.8.2-Post approval stability protocol &
stability commitment. [Q1A&Q5C]
3.2.P.8.3- Stability data
e.g. –tabular , graphical, narrative.
Analytical procedure used to generate data & validation of
these procedures[Q1A,Q1B,Q2A,Q2B&Q5C]
3.2.A-Appendices
3.2.A.1- Facilities and equipment(name , manufacturer)
3.2.A.2-Advantitious agents safety evaluation(name, dosage form,
manufacture)
3.2.A.3- Excipients
3.2.R-REGIONAL INFORMATION
3.3- LITERATURE REFERENCE.

14. Thank you