Quality by Design
Area Coordinators: Parka Glassey and Ranga Godavarti
Quality by Design:
Name: Peter Slade
Name: Arne Staby
Affiliation: Novo Nordisk
A quality by design (QbD) approach for drug development has been a guidance from regulatory agencies since the early 2000s. QbD relies on process understanding by exploring the design space defined as the multidimensional combination and interaction of input variables and process parameters that have been demonstrated to provide assurance of quality. A QbD approach to process developments is advantageous and allows for increased process understanding and regulatory flexibility since working within the design space should not be considered a process change. Defining a design space includes understanding the material attributes and process parameters that affect product critical quality attributes (CQAs). Uncertainty in process understanding/design space can be caused by variability in experimental measurement, differences in equipment, model design and limited ranges, validity of assumptions and differences in scales. This session invites presentations that discuss case studies and QbD approaches used for carrying out process characterization and advanced process understanding during early and late stage biopharmaceutical drug development and production. Relevant topics include regulatory agency filing strategies, risk assessments, qualification of scale-down models, experimental design and analysis, critical process parameter (CPP) classification, evaluation of mathematical process models and defining a design space. Presentations from all API and DP processing areas are invited. Novel drug candidates such as bispecifics, gene therapy products, antibody drug conjugates, non-antibody proteins etc. are encouraged to apply. Also submissions illustrating novel characterization approaches or predictive models are desired.
Name: Paul Dalby
Name: Methal Albarghouthi
The quality target product profile (QTPP) defines the quality characteristics of a biopharmaceutical product that should be achieved to ensure the desired quality, in addition to clinical safety and efficacy. The critical quality attributes (CQAs) are the characteristics that need to be controlled within a certain range to ensure the product quality and clinical performance are maintained. In a Quality by Design (QbD) approach, these CQAs are linked to critical process parameters (CPPs) to form the basis for process and product understanding, and hence the process control that can be used to ensure that the CQAs are within the acceptable range.
This session will address two key questions: How are attribute criticality, and acceptable ranges, determined and what are the challenges in defining them? How is enhanced product understanding leveraged in Regulatory submissions? Case studies are encouraged that highlight approaches for ranking and selecting CQAs for the manufacture of biopharmaceutical drug substances (refrigerated or frozen) and drug products (including lyophilized, pre-filled syringe and auto-injected). Case studies that discuss the leveraging of enhanced product understanding in Regulatory submissions, or that have influenced manufacturing process optimizations and characterization, are also encouraged.
Name: David Robbins
Name: Hong Shen
Affiliation: Janssen (Johnson & Johnson)
A control strategy is a planned set of controls, derived from current product and process understanding, that assures process performance and product quality. Control strategy is established using quality risk management, and should ensure that each critical quality attribute (CQA) is consistently controlled within its acceptable range. The control strategy is based on an understanding of sources of variability that can impact product quality, and typically includes control of input materials, analytical testing controls, and process controls, including critical process parameters (CPPs). Regulatory submissions should describe and justify how the different control elements contribute to the final product quality.
This session will focus on how product and process understanding come together to develop and implement control strategies for protein therapeutics and vaccines. Presentations are invited that exemplify successes or illustrate challenges in establishing, implementing, or evolving a control strategy during a product lifecycle, incorporating a control strategy into a regulatory submission, and/or facilitating flexibility in making a post-licensure manufacturing change.
Relevant topics can include, but are not limited to, the following:
- design of control elements (e.g., process parameters, specifications and in-process tests, materials, and facility/equipment-related)
- methodologies for integrated control strategy
- risk assessment tools associated with developing a control strategy
- examples of deriving appropriate sets of controls for different categories of CQAs
- advances in process analytical technology (PAT) and real-time release (RTR) testing
- continued process verification (CPV) and other innovative approaches to process validation