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? Quality Requirements = need or expectations Target Product Quality Profile Patient (or surrogate) “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 Desired State Knowledge based decisions First Principles Why? MECHANISTIC KNOWLEDGE How? “CAUSAL" KNOWLEDGE What “Causes” What? Need for regulatory oversight CORRELATIVE KNOWLEDGE What Is Correlated to What? Current State DESCRIPTIVE KNOWLEDGE: What?
The New Quality Paradigm – The Evolving Regulatory Framework Product Life Cycle Product Design Process Design Scale-up & Transfer Commercial Manufacture Product ICH Q8/Q8(R) - Pharmaceutical Development PAT Guidance ICH Q9 – Quality Risk Management ICH Q10 – Pharmaceutical Quality Systems
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.
Health authorities change their assessment and inspection
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? 2. CRITICAL QUALITY ATTRIBUTES 3. LINK MAs AND PPs TO CQAS 1. TARGET PRODUCT PROFILE 4. ESTABLISH DESIGN SPACE 6. PRODUCT LIFECYCLE MNGMNT 5. ESTABLISH CONTROL STRATEGY
Step 1. Agree on the Target Product Profile 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). Target 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.
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.
5. 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.