ICH GUIDELINE Q8 PHARMACEUTICAL

DEVELOPMENT

Guided byProf. S. K. Shrivastav

Presented By Bindiya Patel

M.PHARM (PHARMACEUTICS)

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Presentation Outline... Aim

Objective

Introduction

System Before Q8

QbD

ICH Q8 Material Attributes

ICH Q8 Formulation

Contents For 3.2.P.2

Formulation Development Activities

Commercial Manufacturing Activities

Q8 Annexure

Future State Vision

Conclusion

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Objective

To review and study ICH guidelines Q8

To understand the concept of ICH guidelines Q8

To know the importance and study the benefits

of ICH guidelines Q8

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Introduction High level purpose of Q8 is –

1. To provide [harmonised] guidance on the contents of

section 3.2.P.2 (pharmaceutical development) for new

drug products.

2. An opportunity to present the knowledge gained through

the application of scientific approaches to product and

process development (= scientific understanding) .

3. Consult with the appropriate regulatory authorities.

4. Adoption of Q8 philosophies can create a new paradigm

and set of opportunities for Industry and Regulators.

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Cont...

Describes good practices for pharmaceutical

product development

Introduces concepts of� 1. Design space � � 2. Flexible regulatory approaches � 3. Quality Risk Management (Q9) � Does not discuss QbD

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On July 20th 2004 you were told Q8 could deliver…

1. Product quality and performance achieved and

assured by design of effective and efficient

manufacturing processes.

2. Product specifications based on mechanistic

understanding of how formulation and process factors

impact product performance.

3. An ability to effect Continuous Improvement and

Continuous "real time" assurance of quality.

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Cont...

Create a basis of flexible regulatory approaches

by reducing uncertainty.

1. Facilitate risk based regulatory decisions.

2. Continuous improvements without the need

for regulatory review.

3. ”Real time” quality assurance.

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QbD Definition (ICH Q8(R))

A systematic approach to development that begins

with predefined objectives and emphasizes product

and process understanding and process control, based

on sound science and quality risk management.

Design Space : the multidimensional

combination and interaction of input variables (e.g.,

material attributes) and process parameters that have

been demonstrated to provide assurance of quality.

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Design Space Facilitates Regulatory Flexibility

Variable X

Variable Y

Traditional process – limited knowledge – 3 batches, any change needs new data and new approval

New paradigm: influence of factors explored creating knowledge. Risk analysis of impact of change is possible. Approval to move within defined area post-approval could give flexibility for continuous improvement without need for further approval

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Why QbD?

Higher level of assurance of product quality

Cost saving and efficiency for industry � 1. Increase efficiency of manufacturing process

2. Minimize/eliminate potential compliance actions � 3. Provide opportunities for continual improvement� 4. Facilitate innovation � More efficient regulatory oversight

1. Enhance opportunities for first cycle approval.� 2. Streamline post approval manufacturing changes and �

regulatory processes.

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ICH Q8: Material attributes Drug substance

–physicochemical and biological properties in relation to

product performance and manufacturability

Excipients

- concentration, characteristics and functionality in

relation to product performance and manufacturability

- functionality during shelf-life

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ICH Q8: Formulation/Dosage form

Summary describing

1. Pharmaceutical development from initial concept

to final design.

2. Identification of attributes and interacting variables

critical for product quality i.E. Drug substance,

excipients (ranges), container closure system, dosing

device (if relevant), manufacturing process.

3. Formulations from pivotal clinical safety/efficacy

studies.

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Q8 is a 2 part guideline

Part 1Core document Baseline expectationsOptional informationRegulatory Flexibility

RevisionAnnexes relating to specific dosage forms (as Q6a)References to use of risk managementFocus on guiding towards Desired State

Step 4: Nov 2005 Drafting underway

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Q8 applies throughout product life-cycle

Productdevelopmen

t

Technology transfer

Commercialmanufacture

Demonstration of greater under- standing of pharmaceutical and manufacturing sciences can create a basis for flexible regulatory approaches.

Design quality product & process to consistently deliver intended performance.

Manufacturing process improvements, within the approved design space, without further regulatory review.

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Contents for 3.2.P.2 of CTD Quality Module 3

3.2.P.2.1 Components of drug product (drug

substance/ excipients)

3.2.P.2.2 Formulation Dev.

3.2.P.2.3 Manufacturing Process Development

3.2.P.2.4 Container Closure System

3.2.P.2.5 Microbiological Attributes

3.2.P.2.6 Compatibility

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Formulation Development Activities

Activities ICH Q8(R2) – Pharmaceutical DevelopmentRelated Activities

Process Screening • Exploration of unit operations• Characterization of process intermediates

Process Development and Optimization (Lab Scale)

• DOEs for process parameters and interactions with material attributes• Development of Design Space • understanding of critical process operations

Process Development and Optimization (Pilot Scale)

• DOEs for process parameters and interactions with material attributes• Development of Design Space • understanding of critical process operations

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Commercial Manufacturing Activities

Activity ICH Q8(R2) – Pharmaceutical DevelopmentRelated Activities

Technology Transfer • Gain product and process knowledge• Knowledge supports transfer between development and manufacturing to achieve product realization

Commercial Scale Manufacturing for Drug Product

• Definition of commercial process design • Commercial scale runs to verify process design, with additional sampling to verify understanding• Implementation of on-line measurement technologies

Continual Process Verification and Continual Improvement

• On-going analysis and trending of process data, (multivariate SPC, etc.)• Evaluation of process changes and associated effect on intermediates and products

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Q8 Annexure

Define Target Product Profile

Identify ‘CQAs’ – Critical Quality Attributes of Product

Determine QAs of inputs – materials/parameters etc.

Select appropriate process

Determine functional relationships between material

attributes & process parameters to Product CQAs

Identify a control strategy

Propose a “design space”

Define and describe design space in regulatory submission

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Future State Vision: Both Regulators and Industry need to change

REGULATORS INDUSTRY

1. Promote open communication

2. Reviewers who are accessible, engaged, and expert

3. Change the content of applications Encourage knowledge sharing Eliminate non-value added information

4. More science & risk-based evaluation of applications

5. Reduce post-approval change regulatory hurdles

1. Be open and transparent in sharing knowledge: success and failure.

2. Scientists can understand the needs of the Regulators.

3. Change the content of applications.

-Share the knowledge. -Focus on manufacturing

sciences.4. Move to science-based, risk

mitigated applications5. Provide insight into

manufacturing sciences so as to reduce need for post-approval change

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July 2003: An ICH vision

Existing Existing GMPGMP’’ss

Quality by Design(Pharmaceutical

Development)

Quality Risk Management

The Regulatory Quality System

Our vision: The future Pharmaceutical Quality System

Quality Systems

Quality Systems (Q10)

For companies with :1. Good design and

control strategies2. Good Risk

Management strategies3. Good Quality Systems

Quality Risk Management

(Q9)

Quality by Design

(Q8)

Reduced regulatory burden:

• Reduction of submissions on changes/variations

• Inspection of quality systems

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CONCLUSION

Agencies and Industry are moving from ‘blind’ compliance to

‘science and risk-based’ compliance Industry wants this to be

global.

This evolution is based on process understanding and continuous

improvement throughout the product life cycle Traditional

process validation being replaced by a much better alternative.

- Building in quality.

- Continuous quality verification and improvement.

Moving from ‘Quality by Testing’ to ‘Quality by Design’ should,

in principle, allow significant regulatory flexibility helps both

regulators and industry focus on higher risk or added value

activities.

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