QbD approach and Regulatory Challenges in Europe

Transcription

1 QbD approach and Regulatory Challenges in Europe DIA 26th Annual EuroMeeting, Vienna 2014 Dr Peter Richardson Head of Quality, European Medicines Agency An agency of the European Union

2 Disclaimer The views and opinions expressed in the following PowerPoint slides are those of the individual presenter and should not be attributed to Drug Information Association, Inc. ( DIA ), its directors, officers, employees, volunteers, members, chapters, councils, Special Interest Area Communities or affiliates, or any organization with which the presenter is employed or affiliated. These PowerPoint slides are copyright of the European Medicines Agency. Reproduction is permitted provided the source is acknowledged. 1

3 Re-organisation of the EMA Focus on how to better: support the scientific work of the of the EMA committees; share the knowledge and information the Agency holds throughout the EU medicines regulatory network; meet the need of the Agency s stakeholders and partners. Therapeutic area Offices lead Product Teams. Additional functions Offices / Services support to procedures and processes, rationalising activities where possible. Administrative / procedural aspects separated from scientific regulatory support. Quality Office : further integration of chemicals and biologicals.. 2

4 New EMA Structure - Quality Management structure: Divisions / Departments / Offices Human Medicines Research and Development Support Division Human Medicines Evaluation Division, - Scientific and Regulatory Management Department - Specialised Scientific disciplines Department - Quality Office (chemicals and biologicals) Procedure Management and Business Support Division 3

5 What is Quality by Design (QbD) ICH Q8(R2) Systematic approach to development may include, e.g. incorporation of prior knowledge, results of experimental studies using design of experiments, use of quality risk management, and use of knowledge management throughout the lifecycle of product Science applied across the lifecycle of the product / process within a Quality Management System. 4

6 Purpose of QbD? Primarily: Develop robust manufacturing processes, increased understanding of important factors and explanation of sources of variability. Consequently: Provide increased assurance on process control and consistency, may alleviate regulatory oversight. 5

7 Evolution of QbD: ICH Guidelines / Q&A / Training Questions and Answers Points to consider Training & Workshop 6

8 Evolution of QbD: some EU Experiences QWP, BWP, GMP IWG & PAT Group - PAT Group : Landing point for Applicants - Evolving expertise within network More activity for Chemicals v Biologicals Diversity in each application - Expectation, Creativity, Complexity Considerable effort invested International regulator s interacting 7

9 EMA-FDA QbD pilot Aim Allow EU and US assessors exchange their views on the implementation of ICH Q8-10 using actual applications and facilitate harmonisation Share knowledge gained with the EU network and Industry through lessons learnt Japan joined as an observer Scope Submissions that include an enhanced approach to pharmaceutical development leading to the use of at least one of the following: Design space, PAT tools for control, Continuous process verification, Models to support real time release testing, Continuous processes Post-approval regulatory flexibility 8

10 EMA-FDA QbD pilot Two options: Parallel assessment: 1 application complete The application is submitted to both agencies at about the same time, for MAAs/NDAs for parallel evaluation by both agencies Consultative advice: Several ongoing The application is submitted to either EMA or FDA and the agency doing the evaluation requests to obtain consultative advice from the other agency Type of products: Chemicals There are also interactions on biologicals. 9

11 EMA / FDA parallel assessment Renewed for 2 years (until March 2016) 10

12 EMA-FDA Pilot for QbD Progress to Date Applications in program - 1 parallel assessment complete, another accepted - 5 consultative advice - 1 biotech product that followed the consultative advice pathway Meetings - Multiple teleconferences on applications and on general topics - 3 face-to-face meetings Communications - 2 sets of Q&As published, others being developed - Many conference presentations Japanese participation - Parallel assessment application and in multiple meetings 11

13 EMA-FDA QbD Pilot Question & Answers Two sets of Q&As have been published jointly as a result of the pilot (8/20/13 and 11/4/13): Topics include: - Expectations for Quality Target Product Profile (QTPP) - Expectations for Critical Quality Attributes (CQAs) - Classification of criticality in 3 tiers (e.g., Key Process Parameters) - Expectations for the manufacturing process description - Use of QbD for analytical methods (e.g., Analytical Target Profile (ATP) and Method Operational Design Ranges (MODR) - Design space verification 12

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15 Preliminary feedback: QbD Pilot Close Agreement on: - QTPP and CQAs - Criticality - Design Space verification - Level of detail in manufacturing process descriptions - QbD for Analytical Methods 14

16 Quality by Design : Current Status A lot of progress in the recent past - More science based applications - More scientific understanding (DoE), emphasis on Robust manufacturing processes Control Strategy Opportunities: - Real Time Release Testing - Manufacturing flexibility (Design Space) - Focused dossier / reduced variations? 15

17 Quality by Design : issues Problems raised by Regulators and Industry More science but more questions!? Level / amount of data / information requested or submitted in an application not clear. Quality of information submitted in some cases. Why invest in systematic or QbD approach if no benefit? Terminology! 16

18 QbD Workshop - Jan 2014 Six case studies (1 Bio). Team for each composed of industry and regulators. FDA & PMDA repesented. Best practices proposed recommendations. Highly successful, with many participants, also online. Outcomes, presentations and meeting video will be published on Agency website /12/event_detail_ jsp&mid=WC0b01ac058004d5c3

19 Discussion Topics 1. Risk Assessment and Criticality 2. Design Space 3. Use of Models 4. Control Strategy 5. Lifecycle management 6. The Development Story and presentation of Information in Submissions 7. Dossier Quality System interactions 18

20 e.g. Risk Assessment e.g. Risk Assessment FMEA: numbers should be objective however not absolute. Important to provide evidence basis (i.e. the supporting science for proposals). Level of detail needed? 19

21 Perjeta (mab) - EPAR QbD Approach: 20

22 QbD: Challenges and way forward Step 0-1 Investment Immediate benefit : Process understanding Efficiency & yield improvement OOS & Recall decrease Supply Secured Step 1-2 Learning Step 3 full Benefit Training & pilot Trust & predictability Streamline regulatory review Implementation of Regulatory flexibility Regulatory Trust & harmonisation Global Regulatory Alignment Continuous improvement Critical step Post-approval changes Step 0 Step 1 Step 2 Step 3 Investissement Regulatory Challenges Benefits 21 G. France: QbD Workshop Jan14

23 Thank you Peter Richardson Head of Quality Specialised Scientific Disciplines Department European Medicines Agency Acknowledgements: Jean Louis Robert (QWP) Evdokia Korakianiti (EMA) Christine Moore (FDA) Georges France (Novartis) 22