Quality by Design

1. 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

2. QUALITY BY DESIGN processes products

3. 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

4. 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.”

5. 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.”

6. 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

7. 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?

8. 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

9. 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.

11. Advanced drug delivery systems

12. Devices

13. Combination products

14. Active pharmaceutical ingredients

15. Materials incl excipients

17. Universities change their curriculum

19. 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

20. 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.

22. 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.

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

36. the controls of end products contribute to the final product quality

37. 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.