This is a presentation on ICH Q-8 Guideline.also includes what is actually quality by deign with the pharmaceutical industry view.

1. QUALITY BY DESIGN (QBD) AND
PHARMACEUTICAL DEVELOPMENT
Guided By-Asst .Prof. S. Patel Sir.
Presented By-MR .Shubham M. Bhujbal
FY M.Pharm (MQA)
Vishal Institute Of Pharmaceutical
Education And Reasearch,Ale.

2. ICH Q8
PART-1 PHARMACEUTICAL DEVELOPMENT
Objective of the Guideline
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.
The Pharmaceutical Development section provides an
opportunity to present the
knowledge gained through the application of scientific
approaches and quality risk
management (for definition, see ICH Q9) to the development of
a product and its
manufacturing process.

3. PHARMACEUTICAL 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

4. PART II:
PHARMACEUTICAL DEVELOPMENT - ANNEX
INTRODUCTION
This guideline is an annex to ICH Q8 Pharmaceutical Development and
provides
further clarification of key concepts outlined in the core guideline. In
addition, this
annex describes the principles of quality by design1 (QbD). The annex
is not intended
to establish new standards or to introduce new regulatory requirements;
however, it
shows how concepts and tools (e.g., design space1) outlined in the
parent Q8 document
could be put into practice by the applicant for all dosage forms. Where a
company
chooses to apply quality by design and quality risk management (ICH
Q9, Quality
Risk Management), linked to an appropriate pharmaceutical quality
system,
opportunities arise to enhance science- and risk-based regulatory
approaches (see ICH
Q10, Pharmaceutical Quality System).

5. WHAT IS QBD…..?
 Systematic, holistic and proactive
approach to pharmaceutical development.
 Begins with predefined objectives
 Emphasizes product and process
understanding and process control
 Based on sound science and quality risk
management
Ref.: ICH Q8 (R2)

6. WHY QBD……?
 Higher level of assurance of product quality for
patient.
 Improved product and process design
understanding.
 Increases efficiency of manufacturing process.
 Minimize/eliminate potential compliance action.
 Ability to meet FDA submission guidelines and
expectation.
 Reduce Approval time-and fewer queries from
FDA.

7. BACKGROUND OF QBD
In 2002, United States Food and Drug Administration (FDA)
made the first steps towards integrating the QbD concept into
current good manufacturing practices (cGMPs), and in 2004
FDA released its final report on ‘Pharmaceutical cGMPs for
the 21st Century: A Risk Based Approach’ guideline, with the
aim of modernizing the regulation of pharmaceutical
manufacturing and product quality. This pharmaceutical
quality pattern shift is highlighted in the FDA’s ‘Process
Analytical Technology (PAT): Guideline for Industry – A
Framework for Innovative Pharmaceutical Development,
Manufacturing and Quality Assurance’. Besides this, ICH’s
current ‘Q8(R2) Pharmaceutical Development’, ‘Q9 Quality
Risk Management’ and ‘Q10 Pharmaceutical Quality System
Guidelines’ were released in 2009, 2005 and 2008,
respectively. QbD was first introduced into the Chemistry,
Manufacturing and Controls review process in 2004 as a
result of the Pharmaceutical cGMPs for the 21st Century
Initiative[3].

8. HOW QBD WILL HELP TO IMPROVE…?
Ensure higher level of assurance of product quality
for patient
Improved product and process design &
understanding
Monitoring, tracking & trending of product &
process.
More efficient regulatory oversight
Efficiency and cost saving for industry
Increase efficiency of manufacturing process
Minimize / eliminate potential compliance
actions

9. OVERVIEW OF QBD
Quality Target
Product Profile
Product Design
and
Understanding
Process Design
and
Understanding
Control
Strategy
Continuous
Improvement
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10. ELEMENTS OF QBD
 Quality Target Product Profile (QTPP)
 Define Critical Quality Attributes (CQAs)
 Perform risk assessment
 Link raw material attributes and process
parameters to CQAs
 Design and implement a control strategy
 Manage product lifecycle, including continuous
improvement

11. QUALITY TARGET PRODUCT PROFILE
What is QTPP?
A set of elements that defines the drug product
The target or goal set in advance
A guide to Drug Product development
What forms the basis for QTPP?
The RLD and its label
Applicable regulatory guidelines
When to define QTPP?
At the start of development
Knowledge gained in development may change some
elements

12. COMPONENTS OF QTPP
Components related to safety, efficacy, identity, purity
and potency
Critical and non-critical components, e.g.
Critical: Assay, content uniformity
Non-critical: Appearance
Fixed and variable components
Fixed elements must be present
e.g. Dosage form, strength
Variable elements may have a range of acceptable
values
e.g. Tablet weight, assay

13. QTPPAND SPECIFICATIONS
QTPP
 Desired target for developmental work
 Components of QTPP may or may not
be in specification
- Not in spec – Dosage form,
strength
- In spec – Assay, impurities
 Does not include acceptance criteria
Specifications
 Includes all of the CQAs
 Specification is a list of
- tests,
- references to analytical
procedures
- acceptance criteria
 Establishes the set of criteria to
which DP should conform to be
considered acceptable for its
intended use
Defining a QTPP does not mean setting all acceptance criteria
or the product specifications before development work begins.
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14. CRITICAL QUALITY ATTRIBUTES- CQAS
CQAs are a subset of the QTPP
Include critical parameters that are likely to change
based upon variations in raw materials and processes
-Identity test for dosage form – Not a CQA
-Assay, Content uniformity – CQAs
CQAs are monitored throughout the DP
development.
CQAs ensure that DP remains within safe and
effective levels.

15. QTPP AND CQAS
QTPP components
Dosage Form
Route of administration
Strength
Weight
Pharmacokinetics
Appearance
Identity
Assay
Impurities
Content uniformity
Friability
Dissolution
Residual solvents
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CQAs
Assay (efficacy)
Impurities (safety)
C.U. (efficacy)
Dissolution (efficacy)

16. QBD TOOLS – RISK ASSESSMENT
Why risk assessment in product development?
 To identify relative risk levels at the beginning of product
development
 To prioritize limited development resources
 To document the decision making process throughout
development
 To assess the needs of additional studies for scale up and
technology transfer
 To identify appropriate specifications, critical process parameters
and manufacturing controls
 To decrease variability of critical quality attributes
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17. Quality by Design for ANDAs:
An Example for Immediate-Release Dosage Forms
 Generic product development for Acetriptan
Tablets, 20 mg.
 Acetriptan is a BCS Class II compound displaying
poor aqueous solubility (less than 0.015 mg/mL)
across the physiological pH range.
 It exists in three different polymorphic forms which
may affect dissolution.
 Polymorph III is the most stable polymorph.
 Drug product is prepared with roller compaction
process.

18. RISK ASSESSMENT
Risk assessment for
 Formulation – starting material properties, levels of
components
 Manufacturing process
Steps for risk assessment
 List out all components / processes
 Prepare the process flow chart
 Identify all potential failure modes for each item with
risk query (what might go wrong?)
 Risk analysis
 Risk evaluation
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19. Risk assessment for formulation
components
Drug Product CQA
Formulation Variables
Drug Substance
PSD
MCC/Lactose
Ratio
CCS
Level
Talc Level
Magnesium
Stearate Level
Assay MEDIUM MEDIUM LOW LOW LOW
Content Uniformity HIGH HIGH LOW LOW LOW
Dissolution HIGH MEDIUM HIGH LOW HIGH
Degradation
Products
LOW LOW LOW LOW MEDIUM

20. Risk assessment of DP manufacturing
process
Drug Product
CQAs
Process Steps
Pre-RC*
Blending and
Lubrication
Roller
Compaction
Milling
Final Blending
and
Lubrication
Compression
Assay MEDIUM LOW MEDIUM LOW MEDIUM
Content
Uniformity
HIGH HIGH HIGH LOW HIGH
Dissolution MEDIUM HIGH MEDIUM HIGH HIGH
Degradation
Products
LOW LOW LOW LOW LOW

21. Process
Steps
Drug
Product
CQAs
Assigned
Risk
Justification
Pre-Roller
Compaction
Blending
and
Lubrication
Assay MEDIUM
Suboptimal pre-roller compaction blending and lubrication
may cause variable flowability of the blend affecting Assay.
Content
Uniformity
HIGH
The PSD and cohesiveness of the drug substance
adversely impact its flowability. If not blended properly
with excipients, it may affect CU.
Dissolution MEDIUM
Blending process variables may impact the distribution of
CCS in the blend which could impact disintegration of the
granules and ultimately, dissolution of the tablets.
Degradation
Products
LOW
Blending process variables are unrelated to the
degradation products of Generic Acetriptan Tablets, 20 mg.

22. CMAS, CPPS AND CQAS
What factors affect drug product CQAs?
 Properties of Input Materials- Identify Critical Material
Attributes (CMAs)
 Properties of in-process materials- CQAs of one step
become CMAs for a downstream unit operation
 Manufacturing process parameters- Identify Critical
Process Parameters (CPPs)
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Input
Materials
CMAs1
Output
Materials
Product
CQAs
CPPs1
Unit
Operation 1
Unit
Operation 2
CMAs2
CPPs2

23. CONTROL STRATEGY
“A planned set of controls, derived from current product and
process understanding that ensures process performance
and product quality…..”
ICH Q8 (R2) & Q10
Control Strategy includes following elements (but not
limited to):
 Input material attributes (e.g. drug substance, excipients,
container closure)
 Equipment operating conditions (process parameters)
 In-process controls
 Finished product specifications
 Controls for each unit operations
 Methods and frequency of monitoring and control.
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24. CONTROL STRATEGY
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25. REFERENCES FOR QBD
1. Guidance for Industry: Q8(R2) Pharmaceutical Development
2. Guidance for Industry: Q9 Quality Risk Management
3. Guidance for Industry: Q10 Pharmaceutical Quality System
4. Guidance for Industry PAT: A Framework for Innovative
Pharmaceutical Development, Manufacturing, and Quality Assurance
5. Quality by Design for ANDAs: An Example for Modified Release
Dosage Forms
6. Quality by Design for ANDAs: An Example for Immediate Release
Dosage Forms
7. GPhA presentations.
8. Draft QbR updated.
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26. QWERIES…….?

27. THANK YOU