Pharmaceutical Quality & Clinical Research Quality: The Interaction

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Alban Williams
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1 4 th Jerusalem Conference: Quality by Design (QbD)) & Pharma Sciences, May 20-22, 2014 The Edmund Safra Campus, The Hebrew University of Jerusalem Pharmaceutical Quality & Clinical Research Quality: The Interaction By: Dr. Yafit Stark, VP Global Clinical Advisor TEVA Pharmaceutical Industries Ltd.

Pharmaceutical Quality & Clinical Research Quality: The Interaction By: Dr.

2 Introduction/Current Status The Medical Community is raising some concerns regarding safety of medicinal products. There are also reports that the general public is losing confidence in clinical trials. The complexity of clinical trials is increasing in terms of protocols, size, execution and cost reduced efficiency. More outsourcing to 3 rd parties Oversight shifting towards centralized IRB New geographies 2

There are also reports that the general public is losing confidence in clinical trials.

3 Industry & Regulatory Goal Produce and approved to market high quality drug products With minimal regulatory oversight. High benefits and lower risks. By ensuring protection and welfare of our patients. 3

4 The View of the Regulators: EMA & FDA Both are working on moving QbD into studies in humans This is part of the strategy of the agency to develop more robust clinical infrastructure Janet Woodcock. Provide high-quality data strong enough to support the sponsor s labeling claims. 4

develop more robust clinical infrastructure Janet Woodcock.

5 QbD Concept in Clinical Trials QbD is already well recognized and must be in place for manufacturing of medicinal products. The notion of implementing QbD system prospectively into clinical development is more effective than overhauling of processes, changing SOP s and resources retrospectively. Increasing focus on having quality systems in place during planning stages. Systematic approach will produce more reliable and useful data. 5

The notion of implementing QbD system prospectively into clinical development is more effective than

6 What is Quality? Quality is characterized by the ability to effectively and efficiently answer the intended question about the benefits and risks of the medical product (therapeutic or diagnostic) or procedure, while: ensuring protection of human subjects. *Oct. 2008, Dr. Rachel Behrman, CTTI and presently Director of CDE Office of Medical Policy 6

intended question about the benefits and risks of the medical product (therapeutic or

7 Elements of a Quality Clinical Study Scientifically valid and ethically sound experimental design. Adequate protection of subjects rights, safety and welfare. Qualified personnel. Adequate monitoring (local and centralized). Current complete and accurate data. 7

Adequate protection of subjects rights, safety and welfare.

8 Clinical Trials Transformation Initiative (CTTI) A public private partnership (PPP). Established out of shared vision. Mission/Scope: To identify practices that through broad adoption will increase the quality and efficiency of clinical trials. Generate evidence how to improve design and execution. 8

Mission/Scope: To identify practices that through broad adoption will

9 Clinical Trials Transformation Initiative (CTTI) Projects QbD is a major current interest since August Plan to expand beyond drug studies and sponsors. Principles Protect and promote public health. Generate adequate and timely information: Prevention, diagnosis, treatment. Need to protect human subjects and their privacy. Work together to move the system forward. 9

Principles Protect and promote public health.

10 Critical Quality Attributes of Pharmaceuticals Link the product quality to the patient and customer. What the customer needs. And same with specification. *Janet Woodcock, ISP

11 Cost vs. Quality There is a cost to poor quality. Higher quality leads to lower costs. This can be a win-win if done prospectively and correctly. Continuously improve! 11

12 Expectations of Regulatory Authorities from Quality Risk Management (QRM) FDA: EU: Can t inspect in quality retrospectively need to build in prospectively Expect shift from data-heavy NDA/BLA submissions to knowledgerich, i.e. with insights gained from QRM approaches Involve regulators proactively in agreeing quality definitions for programs Identify risks prospectively Comprehensive/holistic approach: Organizational level Project level In clinical program, apply concept at early program design stage, before individual trials are running 12

tively Expect shift from data-heavy NDA/BLA submissions to knowledgerich, i.e. with insights gained from QRM approaches Involve

13 How Can QbD Help in Clinical Drug Development? Quality by Design adds value anywhere where time, cost or quality matters: Designing optimal infrastructure Optimizing processes and systems De-risking clinical programs and individual studies Fit-for-purpose training and communication Enhancing GCP compliance and reducing audit/inspection findings Meeting health authority expectations Reducing costly errors Getting it right first time minimizing need for laborious fixes 13

processes and systems De-risking clinical programs and individual studies Fit-for-purpose training and communication

14 Project Risk Management Plan Ideally, should be included in project management plan Can be simple, informal, e.g. Risk sources reviewed Risks identified Mitigation plans Formal risk management plan should contain plans and procedures for: Sources of risk and risk identification Risk analysis (impact, probability, detectability) Risk response planning Risk monitoring and control 14

Risk sources reviewed Risks identified Mitigation plans Formal risk management plan should

15 Conclusions Innovations in study designs are critical for success of clinical development: Simulations Adaptive Designs Bayesian Networks New initiatives to translate animal data into early human testing are underway (IVIVC) More management maturity (on the Quality Ladder) Expanded application of QbD in pharmaceutical industry Build in quality in advance instead of fixing things afterwards Evan a simple risk management plan is better than nothing Start as far upstream as possible and think holistically Update the project RMP periodically, e.g. at milestones/phase transitions Use project RMP in communications with management Use project RMP in de-brief at project end Structured RMP for all projects allows systemic findings across organization Establish a culture of proactive risk management and what if thinking 15

16 Conclusions (contd.) Quality by Design in Clinical Development Do we wish to have a new concept? Foster clinical development Maximize success in clinical development Ensure safety and effectiveness making successful drugs available for unmet needs QbD is a strategic/systemic approach in improving product development to maximize the success of getting new products to the market:» faster» safer» smarter» and for less!!! 16

making successful drugs available for unmet needs QbD is a strategic/systemic approach in improving

Quality by Design Concept

Quality by Design Concept 3rd Jerusalem Conference on Quality and Pharma Sciences 6-7 June, 2012 QbD in Clinical Research - Where Can QbD Impact Clinical Research Practices? Dr. Yafit Stark Vice President, TEVA Pharmaceutical Industries,