ICH Guideline Q8 Pharmaceutical Development

ICH Guideline Q8 Pharmaceutical Development

1. ICH Guideline Q8 Pharmaceutical Development Guided by Prof. S. K. Shrivastav Presented By Bindiya Patel M.PHARM (PHARMACEUTICS)

2. 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 2

3. 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 3

4. Introduction High level purpose of Q8 is – To provide [harmonised] guidance on the contents of section 3.2.P.2 (pharmaceutical development) for new drug products. An opportunity to present the knowledge gained through the application of scientific approaches to product and process development (= scientific understanding) . Consult with the appropriate regulatory authorities. Adoption of Q8 philosophies can create a new paradigm and set of opportunities for Industry and Regulators. 4

5. 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 5

6. On July 20 th 2004 you were told Q8 could deliver… Product quality and performance achieved and assured by design of effective and efficient manufacturing processes. Product specifications based on mechanistic understanding of how formulation and process factors impact product performance. An ability to effect Continuous Improvement and Continuous "real time" assurance of quality. 6

7. 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. 7

8. 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. 8

9. Design Space Facilitates Regulatory Flexibility 9 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

10. 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. 10

11. 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 11

12. 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. 12

13. Q8 is a 2 part guideline Part 1 Core document Baseline expectations Optional information Regulatory Flexibility 13 Revision Annexes relating to specific dosage forms (as Q6a) References to use of risk management Focus on guiding towards Desired State Step 4: Nov 2005 Drafting underway

14. Q8 applies throughout product life-cycle 14 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.

15. 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 15

16. Formulation Development Activities Activities ICH Q8(R2) – Pharmaceutical Development Related 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 16

17. Commercial Manufacturing Activities Activity ICH Q8(R2) – Pharmaceutical Development Related 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 17

18. 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 18

19. Future State Vision: Both Regulators and Industry need to change REGULATORS INDUSTRY Promote open communication Reviewers who are accessible, engaged, and expert Change the content of applications Encourage knowledge sharing Eliminate non-value added information More science & risk-based evaluation of applications Reduce post-approval change regulatory hurdles Be open and transparent in sharing knowledge: success and failure. Scientists can understand the needs of the Regulators. Change the content of applications. -Share the knowledge. -Focus on manufacturing sciences. Move to science-based, risk mitigated applications Provide insight into manufacturing sciences so as to reduce need for post-approval change 19

20. July 2003: An ICH vision 20

21. 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. 21

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