Presentation on Quality by Design

‘Pharmaceutical GMPs

for the 21st Century’

By: Akhilesh Kumar Dwivedi

Dr. Reddy’s Labs. F.T.O-III

Date: 18 Jan 2011

QUALITY BY DESIGN

QUALITY BY DESIGN

processes products

HISTORY: Quality by Design (QbD) is a concept first outlined by well-known quality expert Joseph M. Juran in various publications, most notably Juran on Quality by Design. Juran believed that quality could be planned, and that most quality crises and problems relate to the way in which quality was planned in the first place.

QUALITY BY DESIGN

What is Quality?

Requirements= need or expectations

Quality

Patient(or surrogate)

Target ProductQuality Profile

“Good pharmaceutical quality represents an acceptably low risk of failing to achieve

the desired clinical attributes.”

The quality mantra

“Quality can not be tested into

products; it has to be built in

by design”

“Quality is never an accident; it is always the result of high intention, sincere effort, intelligent direction and skillful execution; it represents the wise choice of many alternatives.”

How can we modernize our industry?

More knowledge of our products and processes, allowing better design and more control

Better management:- introduction of quality risk management- expansion of GMP to more extensive pharmaceutical quality system

The knowledge pyramid

CORRELATIVE KNOWLEDGEWhat Is Correlated to What?

“CAUSAL" KNOWLEDGEWhat “Causes” What?

MECHANISTICKNOWLEDGE

How?

DESCRIPTIVE KNOWLEDGE: What?

Need

for

reg

ula

tory

overs

igh

t

Kn

ow

led

ge b

ase

d d

ecisio

ns

Desired State

Current State

FirstPrinciples Why?

The New Quality Paradigm – The Evolving Regulatory Framework

ICH Q8/Q8(R) - Pharmaceutical Development

PAT Guidance

ICH Q9 – Quality Risk Management

ICH Q10 – Pharmaceutical Quality Systems

ProductDesign

Process Design

Scale-up &Transfer

Commercial Manufacture

Product Life Cycle

Product

Definition: Quality by Design

Quality by Design is 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.

Quality by Design approach can be used for

• Simple dosage forms

• Advanced drug delivery systems

• Devices

• Combination products

• Active pharmaceutical ingredients

• Materials incl excipients

• Analytics

• Companies re-organize their science

• Universities change their curriculum

• Health authorities change their assessment and inspection

Impact of QbD

QUALITY BY DESIGN

Step 1. Agree on the Target Product Profile

Step 2. Determine the Critical Quality Attributes (CQAs)

Step 3. Link the drug and excipient attributes and the

process parameters to the CQAs

Step 4. Define the Design Space

Step 5. Define the Control Strategy

Step 6. Prepare QbD registration file

Step 7. Product lifecycle management and

continual improvement

What are the steps in aQuality by Design approach?

What are the steps in aQuality by Design approach?

1. TARGET PRODUCT PROFILE

2. CRITICAL QUALITY

ATTRIBUTES

6. PRODUCT LIFECYCLE

MNGMNT

3. LINK MAs AND PPs

TO CQAS

5. ESTABLISHCONTROL STRATEGY

4. ESTABLISHDESIGN SPACE

Step 1. Agree on the Target Product

ProfileTarget Product Profile: - a prospective and dynamic summary of the quality characteristics of a drug product - that ideally will be achieved to ensure that the desired quality, and hence the safety and efficacy, of a drug product is realized.

The TPP forms the basis of design of the product.

Consider: dosage form route of administration strength release / delivery of

the drug pharmacokinetic

characteristics (e.g., dissolution; aerodynamic performance)

drug product quality criteria (e.g., sterility, purity).

CRITICAL QUALITY ATTRIBUTES - definition

CRITICAL QUALITY ATTRIBUTES - definition

A critical quality attribute (CQA) is a - physical, chemical, biological, or microbiological property or characteristic - that should be within an appropriate limit, range, or distribution - to ensure the desired product quality.

Step 4. Define the Design SpaceStep 4. Define the Design Space

The linkage between - the process inputs (input variables and process parameters) and - the critical quality attributes

can be described in the design space.

Definition of Design SpaceDefinition of Design Space

The material attributes and process parameters that assure quality.

The multidimensional combination and interaction of input variables (e.g. material attributes) and process parameters that have beendemonstrated to provide assurance of quality.

Roll

pre

ssure

Gap width

Screen Size

Step 5. Define the Control StrategyStep 5. Define the Control Strategy

The control strategy should describe and justify how

in-process controls and

the controls of - input materials (drug substance and excipients), - container closure system, - intermediates and

the controls of end products

contribute to the final product quality

5. CONTROL STRATEGY5. CONTROL STRATEGY

Elements of a control strategy can include, but are not limited to, the following:

• Control of input material attributes (e.g., drug substance, adhesive polymer, primary packaging materials) based on an understanding of their impact on processability or product quality

• Product specification(s)

• Controls for unit operations that have an impact on downstream processing or end-product quality (e.g., the impact of solvent on degradation)

• In-process or real-time release in lieu of end-product testing

• A monitoring program (e.g., full product testing at regular intervals) for verifying multivariate prediction models.