Quality Tolerance Limits as Required by ICH E6(R2): Definitions and Requirements for “Fit-For-Purpose” Compliance

Expectations for quality tolerance limits when conducting Good Clinical Practice (GCP) clinical trials in accordance with ICH E6(R2) have generated a buzz in the industry. Quality tolerance limits have historically been required for Good Manufacturing Practice (GMP) activities, inferring limits by which significant actions must be taken to ensure the manufactured product achieves quality and usability limits. With regulators now using the same terminology for GCP clinical studies, what is truly expected?

ICH E6(R2) describes in Section 5.0.4: “The Sponsor should decide which risks to reduce and/or which risks to accept. The approach used to reduce risk to an acceptable level should be proportionate to the significance of the risk…Predefined quality tolerance limits should be established, taking into consideration the medical and statistical characteristics of the variables as well as the statistical design of the trial, to identify systematic issues that can impact subject safety or reliability of trial results. Detection of deviations from the predefined quality tolerance limits should trigger an evaluation to determine if action is needed.”

This interactive webinar will clarify terminology, including metrics, performance indicators, and tolerance limits. It will also provide insights about relevant clinical trial parameters that merit quality tolerance limits, approaches to establish appropriate limits, and methodology for monitoring and controlling study activities to minimize risk and likelihood to reach tolerance limits that warrant action.

Leading practices within The Avoca Quality Consortium (AQC), with insights from nearly 100 member companies, provide a wealth of information for setting and managing quality tolerance limits. A “fit-for-purpose” fashion takes into account differences between study phase, complexities, and also company size (e.g. large pharma relative to small biotech). Concepts for applying fit-for-purpose perspectives will be shared, including practical approaches for engaging clinical study teams across the boundaries of sponsor, provider, and investigative sites.

Key takeaways will include:

• Clarification of definitions surrounding quality tolerance limits for GCP clinical trials
• Types of parameters that warrant quality tolerance limits
• Effective management of risk using performance indicators and quality tolerance limits
• “Fit-for-purpose” concepts for applying quality tolerance limits across phases of clinical trials and sponsor type

To learn more about Quality Tolerance Limits, read Avoca’s blog, “What Are Quality Tolerance Limits (QTLs) and Why Are They Important?”

Speakers

Jay A. Turpen, Senior Consultant, The Avoca Group

Jay Turpen is a Senior Consultant with The Avoca Group. He has been in the pharmaceutical industry for 29 years and has held various leadership roles. Jay has a wealth of experience in GMP, GLP, and GCP environments with significant real-life experience in developing numerous new drug candidates.

His pharma experience started in GMP of small molecule and large molecule (biologic) active pharmaceutical ingredients (API). Jay has been involved in leading multiple clinical teams responsible for the clinical development and NDA preparation for multiple molecules in osteoporosis, diabetes, cardiovascular, neuroscience, and immunology. Jay also led a transformation effort for his company’s CLO organization that affected processes, systems, job definitions/descriptions, and organizational leadership to meet both GLP and GCP requirements.

Most recently, Jay was Senior Director for Clinical Project Management (CPM) where he was responsible for the clinical development for Alzheimer’s disease, autoimmune diseases, men’s health, pain, and other neuroscience indications. This CPM organization, under Jay’s leadership, successfully completed multiple NDA submissions, regulatory agency inspections, and received regulatory approvals for small molecule and biologic products demonstrating thorough GCP compliance. Jay retired from Eli Lilly & Co. at the end of 2017 where he was Sr. Director, Clinical Project Management – Biomedicines.

Message Presenter

Steven B. Whittaker, Senior Consultant, The Avoca Group and Executive Director, the Avoca Quality Consortium, 2011-2018

Steve Whittaker is a Senior Consultant with The Avoca Group, and former Executive Director of the Avoca Quality Consortium. He is also a lead consultant for the pharmaceutical, biotech, and CRO industries providing expertise in project management, pharmaceutical development, clinical development, outsourcing strategies and execution plans. His experience through years of drug development leadership roles, combined with his established professional network across these industries, provides unique and valuable insights for organizational leaders.

Steve served as Executive Director of the Avoca Quality Consortium from 2011-2018, and for 14 consecutive years on the Advisory Board for the annual Partnerships in Clinical Trials program, chairing the board for two years. In addition, he has moderated numerous quarterly Clinical Research Consortium forums, developing strategic agendas and facilitating the exchange of leadership concepts between clinical development executives across top-tier pharmaceutical and biotech organizations.

In 2009, Steve retired from Eli Lilly and Company, where he served as Chief Operating Officer/Sr. Director of Operations and Project Management for the Cardiovascular/Acute Care Platform. As the leader of the Global Clinical Research Sourcing Office, Steve established Lilly’s first corporate strategy and operational design for outsourcing global clinical development to CRO preferred partners. This included the selection and initial implementation of the preferred partner approach for global, full-service CRO capabilities. Steve also led Lilly’s Project Management Center of Excellence, establishing standards for leaders of project development.

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