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Dr Joachim Ermer, Sanofi, Germany
Patrick Jackson, GSK, United Kingdom
The aim of this two-day course is to provide guidance on how QbD principles can be applied to analytical methods and identify the opportunities, not only for new development products, but also for drugs already marketed. This course will deal among others with the following questions:
What are the opportunities of applying QbD and life cycle approach to analytical methods?
What is the current status and future expectations of analytical QbD and life cycle management (USP, FDA-EMA, FDA Guidance Method Validation)?
How can the Analytical Target Profile increase regulatory flexibility?
Why is it important to have a clear understanding and expectation of method performance?
What is the impact of QbD on method development, validation and transfer?
What is the advantage of the 3-Stage life cycle approach to validation?
What are expectations and practical approaches to Stage 3, Continued Method Verification?
How can QbD also benefit marketed products?
A number of interactive workshops will be provided throughout the two days which will enable delegates to apply what they have learned and to discuss the concepts in more detail. Delegates will have the opportunity to work through the whole QbD process by gaining “hands-on experience” using a number of case studies.
The pharmaceutical industry is currently embracing QbD concepts to help improve the robustness of manufacturing processes and to facilitate continuous improvement strategies to enhance product quality and manufacturing productivity. QbD ensures product quality and requires process performance characteristics to be scientifically designed to meet specific objectives, not merely empirically derived from the performance of test batches. Key QbD concepts are described in ICH guidelines Q8 (R1) Pharmaceutical Development, Q9 Quality Risk management and Q10 Pharmaceutical Quality System. The same opportunities exist for applying QbD to analytical methods as they do for manufacturing processes.
During the course, an overview of a position paper written jointly by PhRMA and EFPIA and of a USP Stimuli Article will be provided. These two documents use the now increasingly accepted Analytical Target Profile (ATP) concept. It parallels the Quality Target Product Profile described and defined in ICH Q8 and defines the performance requirements for the measurement of a given Quality Attribute. The ATP can be used to drive all analytical life cycle activities within the three stages (Method Design, Method Performance Qualification, Continued Method Performance Verification) including change control.
It is hoped that greater continuous improvement of methods can also be facilitated if regulatory authorities agree with and approve the ATP statement. Each method conforming to the ATP requirements would be implemented by the company’s internal change control management system, thus providing regulatory flexibility. Risk assessment tools and statistical methods used to facilitate understanding of the method performance characteristics (e.g. accuracy and precision) and their acceptance criteria will also be covered.
Aligned with the modern approach to process validation, increasing attention is given to ensure that “the procedure should be followed during the life cycle of the product to continually assure that it remains fit for its intended purpose” (FDA Method Validation Guidance). Performance parameters as well as acceptance criteria to establish a rational and efficient monitoring and trending are closely related to a sound method understanding as part of the QbD approach.
Note: In order to fully benefit from the workshops, attendees should preferably bring a notebook with Excel®.
This course is designed for analytical managers and scientists who are responsible for performing or reviewing activities like method development, validation, transfer, operation and monitoring of methods in a QC environment, statistical evaluation of method performance, analytical change control etc.
In addition, QA and regulatory affairs professionals will benefit from this course by gaining an understanding in future CMC trends. This will aid more effective multifunctional discussions on these topics within industry.
Introduction to Analytical Quality-by-Design and
life cycle management
Overview on proposals of EFPIA/PhRMA Paper and USP Stimuli Article
Analytical Target Profile
Application of QbD principles to pharmaceutical analysis
Change Control and regulatory flexibility
Stages of the validation life cycle approach
-Continued Method Verification
Design Intent of the Method – ATP and Business
Linkage with process control strategy (critical quality attributes)
Definition of ATP
Method Performance Characteristics and their criteria
Business requirements of method
Understanding the ATP – Analytical Variability
Sources of analytical variability
Method performance characteristics: accuracy and precision
Precision of the reportable result and impact on the analytical control strategy
Method performance and expectation ranges for experimental results and statistical parameters
Decision rules and establishment of acceptance limits
QbD Method Development
Control Definition of method (robustness and ruggedness testing)
Traditional Validation versus QbD Validation
“Translation” of ATP into specific method requirements
Identification of relevant performance parameters
Establishment of appropriate acceptance criteria
Suitable parameters for continued performance verification
Life cycle and change management
Knowledge management system
Analytical Method Transfer
Routine method operation
Continuous method verification, change control and regulatory implications
Wrap up & Final Discussion
The concepts and tools used over the two days will be summarized and future implications and opportunities of applying QbD and life cycle management principles to analytical measurements will be discussed. Delegates will be given time to ask questions on how they can apply what they have learned to their own analytical methods.
Workshop on Variability
Application of statistical simulations
Gain experience (“feeling”) for the consequences of variability
Method performance: statistical measures for precision, accuracy, linearity
Probability of OOS and out-of-acceptance criteria situations
Workshop Risk Assessment
Use of fishbone diagrams
Identification of controllable factors, noise factors and experimental parameters (CNX)
Use of priority matrix and failure mode and effects analysis (FMEA)
Workshop Case Studies
Starting from provided ATPs for several critical quality attributes, delegates will be split into small groups in order to discuss how each ATP is translated into meth- od specific performance characteristics and acceptance criteria. The delegates will identify suitable parameters to monitor the continued performance of the selected procedure. Examples of critical quality attributes will be used such as
Identification of an API in a tablet formulation
Assay of drug substance
Water content in drug substance
Determination of degradants in drug product