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BACKGROUND 
•ICH established in 1990 as joint industry/ 
regulatory project to improve through 
harmonization the efficien...
Pharmaceutical Quality System 
The Regulatory 
Quality System 
Quality by Design 
(Pharmaceutical 
Development) 
Quality R...
Q8– an opportunity for change 
Traditional Future 
Empirical 
Data Driven 
Retrospective 
“Test to document 
quality” 
Acc...
TABLE CONTENTS 
1. Introduction 
1.1 Objective 
2. Pharmaceutical Development 
2.1 Components of Drug Product 
2.1.1 Drug ...
The Pharmaceutical Development 
section provides an opportunity to 
present the knowledge gained 
through the application ...
OBJECTIVE 
This guideline describes the suggested contents 
for the 3.2.P.2 (Pharmaceutical Development) 
section of a reg...
P 
H 
A 
R 
M 
A 
C 
E 
U 
T 
I 
C 
A 
L 
DEVELOPMENT 
The aim of pharmaceutical 
development is to design a quality 
pro...
COMPONENTS 
OF 
DRUG PODUCT 
2.1.1 
DRUGSUBSTANCES 
2.1.2 
EXCIPIENTS
DRUG SUBSTANCES 
“The physicochemical and biological properties of the 
drug substance that can influence the performance ...
EXCIPIENTS 
The excipients chosen, their concentration, and the 
characteristics that can influence the drug product 
per...
DRUG PODUCT 
2.2.1 
FORMULATION 
DEVELOPMENT 
2.2.2 
OVERAGES 
2.2.3 
PHYSIOCHEMICAL 
& BIOLOGICAL 
PROPERTIES
FORMULATION DEVELOPMENT 
A summary should be provided describing the development 
of the formulation, including identific...
OVERAGES 
Overages in the manufacture of the drug product, whether 
they appear in the final formulated product or not, sh...
PHYSIOCHEMICAL & BIOLOGICAL 
PROPERTIES 
The physicochemical and biological properties relevant 
to the safety, performan...
M 
A 
N 
U 
F 
A 
C 
T 
U 
R 
I 
N 
G 
PROCESS 
DEVELOPMENT 
Important consideration to critical 
formulation attributes,...
C 
O 
N 
T 
A 
I 
N 
E 
R 
CLOSURE 
SYSTEM 
The choice for selection of the 
container closure system for the 
commercial...
M 
I 
C 
R 
O 
B 
I 
O 
L 
O 
G 
I 
C 
A 
L 
ATTRIBUTES 
The selection and effectiveness of 
preservative systems in prod...
C 
O 
M 
P 
A 
T 
I 
B 
I 
L 
I 
T 
Y 
The compatibility of the drug product 
with reconstitution diluents (e.g., 
precipi...
DEVELOPMENT PARADIGM – 
Target 
Product 
Profile 
Product/ 
Process 
Dev. 
Product/ 
Process 
Design 
Space 
Control 
Stra...
1. TARGET 
PRODUCT 
PROFILE 
2. CRITICAL 
QUALITY 
ATTRIBUTES 
3. LINK 
MAs AND PPs 
TO CQAS 
4. ESTABLISH 
DESIGN 
SPACE ...
“It is relative amount of drug from an administered 
dosage form which enters the systemic circulation and 
rate at which ...
May have a drug with very low bioavailability . Dosage form 
or drug may not dissolve readily . Drug may not be readily 
p...
“Pharmaceutical Equivalents contain the same amount 
of the same active substance in the same dosage form 
meet the same o...
“Two products are bioequivalent if they are pharmaceutically 
equivalent bioavailabilities (both rate and extent) after 
a...
ICH Q8 " PHARMACEUTICAL DEVELOPMENT"
ICH Q8 " PHARMACEUTICAL DEVELOPMENT"
ICH Q8 " PHARMACEUTICAL DEVELOPMENT"
ICH Q8 " PHARMACEUTICAL DEVELOPMENT"
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ICH Q8 " PHARMACEUTICAL DEVELOPMENT"

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This presentation provides you brief overview of ICH Q8 guideline on Pharmaceutical Development.

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ICH Q8 " PHARMACEUTICAL DEVELOPMENT"

  1. 1. BACKGROUND •ICH established in 1990 as joint industry/ regulatory project to improve through harmonization the efficiency of the process for developing and registering new medicinal products •The Fourth International Conference on Harmonization (ICH 4), Brussels, 1997 marks the completion of the first phase •It was agreed that the second phase of harmonization continue to ensure the future activities of ICH
  2. 2. Pharmaceutical Quality System The Regulatory Quality System Quality by Design (Pharmaceutical Development) Quality Risk Management Quality Systems Existing GMP’s Quality Systems (Q10) For companies with : 1. Good design and control strategies 2. Good Risk Management strategies 3. Good Quality Systems Quality Risk Management (Q9) Quality by Design (Q8) Reduced regulatory burden: • Reduction of submissions on changes/variations • Inspection of quality systems
  3. 3. Q8– an opportunity for change Traditional Future Empirical Data Driven Retrospective “Test to document quality” Acceptance criteria based on limited batch data Variability not understood and avoided Q8 Systematic Knowledge driven Prospective Science and Risk based Acceptance criteria based on patient needs Variability explored and understood (Design Space)
  4. 4. TABLE CONTENTS 1. Introduction 1.1 Objective 2. Pharmaceutical Development 2.1 Components of Drug Product 2.1.1 Drug Substance 2.1.2 Excipients 2.2 Drug Product 2.2.1Formulation Development 2.2.2 Overages 2.2.3 Physiochemical and Biological Properties 2.3 Manufacturing Process Development 2.4 Container Closure System 2.5 Microbial Attributes 2.6 Compatibility
  5. 5. The Pharmaceutical Development section provides an opportunity to present the knowledge gained through the application of scientific approaches and quality risk management to the development of a product and its manufacturing process. I N T R O D U C T I O N
  6. 6. OBJECTIVE This guideline describes the suggested contents for the 3.2.P.2 (Pharmaceutical Development) section of a regulatory submission in the ICH M4 Common Technical Document (CTD) format.
  7. 7. P H A R M A C E U T I C A L DEVELOPMENT The aim of pharmaceutical development is to design a quality product and its manufacturing process to consistently deliver the intended performance of the product. The information and knowledge gained from pharmaceutical development studies and manufacturing experience provide scientific understanding to support the establishment of the design space, specifications, and manufacturing controls.
  8. 8. COMPONENTS OF DRUG PODUCT 2.1.1 DRUGSUBSTANCES 2.1.2 EXCIPIENTS
  9. 9. DRUG SUBSTANCES “The physicochemical and biological properties of the drug substance that can influence the performance of the drug product and its manufacturability.” Examples of physicochemical and biological properties that might need to be examined include •Solubility, •Water content, •Particle size, •Crystal properties, •Biological activity, •Permeability.
  10. 10. EXCIPIENTS The excipients chosen, their concentration, and the characteristics that can influence the drug product performance or manufacturability should be discussed relative to the respective function of each excipients. The compatibility of the drug substance with excipients should be evaluated. For products that contain more than one drug substance, the compatibility of the drug substances with each other should also be evaluated.
  11. 11. DRUG PODUCT 2.2.1 FORMULATION DEVELOPMENT 2.2.2 OVERAGES 2.2.3 PHYSIOCHEMICAL & BIOLOGICAL PROPERTIES
  12. 12. FORMULATION DEVELOPMENT A summary should be provided describing the development of the formulation, including identification of those attributes that are critical to the quality of the drug product and also highlight the evolution of the formulation design from initial concept up to the final design. Information from comparative in vitro studies (e.g., dissolution) or comparative in vivo studies (e.g., BE) that links clinical formulations to the proposed commercial formulation. A successful correlation can assist in the selection of appropriate dissolution acceptance criteria, and can potentially reduce the need for further bioequivalence studies following changes to the product or its manufacturing process.
  13. 13. OVERAGES Overages in the manufacture of the drug product, whether they appear in the final formulated product or not, should be justified considering the safety and efficacy of the product. Information should be provided on the 1) Amount of overage, 2) Reason for the overage (e.g., to compensate for expected and documented manufacturing losses), 3) Justification for the amount of overage.
  14. 14. PHYSIOCHEMICAL & BIOLOGICAL PROPERTIES The physicochemical and biological properties relevant to the safety, performance or manufacturability of the drug product should be identified and discussed. This includes the physiological implications of drug substance and formulation attributes.
  15. 15. M A N U F A C T U R I N G PROCESS DEVELOPMENT Important consideration to critical formulation attributes, together with the available manufacturing process options, in order to address the selection of the manufacturing process and confirm the appropriateness of the components. Appropriateness of the equipment used for the intended products should be discussed. The manufacturing process development programme or process improvement programme should identify any critical process parameters that should be monitored or controlled (e.g., granulation end point) to ensure that the product is of the desired quality.
  16. 16. C O N T A I N E R CLOSURE SYSTEM The choice for selection of the container closure system for the commercial product should be discussed. The choice of materials for primary packaging and secondary packaging should be justified. A possible interaction between product and container or label should be considered.
  17. 17. M I C R O B I O L O G I C A L ATTRIBUTES The selection and effectiveness of preservative systems in products containing antimicrobial preservative or the antimicrobial effectiveness of products that are inherently antimicrobial.  For sterile products, the integrity of the container closure system as it relates to preventing microbial contamination. The lowest specified concentration of antimicrobial preservative should be justified in terms of efficacy and safety, such that the minimum concentration of preservative that gives the required level of efficacy throughout the intended shelf life of the product is used.
  18. 18. C O M P A T I B I L I T Y The compatibility of the drug product with reconstitution diluents (e.g., precipitation, stability) should be addressed to provide appropriate and supportive information for the labeling.
  19. 19. DEVELOPMENT PARADIGM – Target Product Profile Product/ Process Dev. Product/ Process Design Space Control Strategy Define product intended use & quality targets (wrt efficacy & safety) Incorporate prior knowledge, Risk Assessment, DoE and PAT to create New Scientific Knowledge, Through hypothesis testing, create scientific understanding of product and process. Identify ’critical to quality attributes’ and establish multi-variate ”Design Space” that assures Quality Define control strategy based on Quality Risk Mgmt & Design Space leading to control of quality relevant to safety and efficacy. QUALITY BY DESIGN
  20. 20. 1. TARGET PRODUCT PROFILE 2. CRITICAL QUALITY ATTRIBUTES 3. LINK MAs AND PPs TO CQAS 4. ESTABLISH DESIGN SPACE 5. ESTABLISH CONTROL STRATEGY 6. PRODUCT LIFECYCLE MNGMNT
  21. 21. “It is relative amount of drug from an administered dosage form which enters the systemic circulation and rate at which the drug appears in the systemic circulation. The extent and rate at which its active moiety is delivered from pharmaceutical form and becomes available in the systemic circulation.”
  22. 22. May have a drug with very low bioavailability . Dosage form or drug may not dissolve readily . Drug may not be readily pass across biological membranes (i.e. be absorbed) . Drug may be extensively metabolized during absorption process (first-pass, gut wall, liver) . Important component of overall variability i.e. Variable bioavailability may produce variable exposure.
  23. 23. “Pharmaceutical Equivalents contain the same amount of the same active substance in the same dosage form meet the same or comparable standards intended to be administered by the same route Pharmaceutical equivalence by itself does not necessarily imply therapeutic equivalence.”
  24. 24. “Two products are bioequivalent if they are pharmaceutically equivalent bioavailabilities (both rate and extent) after administration in the same molar dose are similar to such a degree that their effects can be expected to be essentially the same.” “Therapeutic equivalence Two products are therapeutically equivalent if pharmaceutically equivalent their effects, with respect to both efficacy and safety, will be essentially the same as derived from appropriate studies bioequivalence studies pharmacodynamic studies clinical studies in vitro studies”

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