Quality by Design using Design of Experiments

[John Robinson]

The Q8, which is the ICH guidance document on pharmaceutical development, requires a drug product to meet its intended product performance as well as the needs of patients. A drug product is encouraged to adapt a systematic approach for pharmaceutical development in accordance with the steps defined by Quality by Design (QbD) principles, even though the strategy may vary from company to company or from product to product.

The ICH has offered further guidance and policies for explaining the ways by which the QbD approach should be integrated into the pharmaceutical Quality System. Some of these are:

o  Process design

o  Qualification

o  Continued process verification

o  Risk management

o  Validation.

Laxity in implementation is no longer an option

Despite the issuance of guidance on implementation of these requirements; many companies have not yet implemented QbD into their Quality Systems. This will change soon, though. Regulatory agencies have been taking a serious view of non-implementation of these requirements.

The ways in which reviewers will begin to enforce the requirements from these guidance documents have been spelt out in the manual the Chemistry, Manufacturing, and Controls (CMC) reviewers in the Office of Pharmaceutical Science (OPS) released on policies and procedures (MAPP).

The zeal with which the regulatory agencies will enforce compliance with the requirements of the QbD requirements has been emphasized also by the Director of the Center for Drug Evaluation and Research (CDER) at the FDA, who detailed the concept and reiterated the importance of using a QbD approach to pharmaceutical development in a paper he co-authored in The American Association of Pharmaceutical Scientists in May 2014.

Understand the ways of implementing QbD

In the light of the fact that a drug product can no longer afford to relax in its adherence to steps defined by Quality by Design (QbD) principles to adapting a systematic approach for pharmaceutical development; a meaningful and educative two-day seminar from GlobalCompliancePanel, a leading provider of professional trainings for the areas of regulatory compliance, will show the ways of doing this.

At this seminar, Heath Rushing, who is the cofounder of Adsurgo LLC and co-author of the book Design and Analysis of Experiments by Douglas Montgomery: A Supplement for using JMP, will be the Director. To gain complete insight into how to implement QbD, please register for this seminar by visiting Quality by Design using Design of Experiments. This seminar has been pre-approved by RAPS as eligible for up to 12 credits towards a participant's RAC recertification upon full completion.

Complete learning on QbD using DoE

The core purpose of this session is to demonstrate how to integrate those QbD principles into a pharmaceutical Quality System. Towards this end, Heath will focus on how to establish a systematic approach to pharmaceutical development that is defined by Quality-by-Design (QbD) principles using Design of Experiments (DoE).

He will also take up the application of statistics for setting specifications, assessing measurement systems (assays), developing a control plan as part of a risk management strategy, and ensuring process control/capability for detailed description. All concepts are taught within the product Quality System framework defined by requirements in regulatory guidance documents.

A systematic understanding of the process

A QbD approach for pharmaceutical development studies should include a systematic understanding of the process. It should then use this understanding to establish a control strategy as part of a comprehensive quality risk management program. This systematic understanding should include both identification of significant process parameters and determination of a functional relationship (mathematical model) linking these significant process parameters to the critical Quality Attributes (CQAs). Heath will discuss these in depth.

Despite the thrust of this seminar on the use of DoE for QbD; it will integrate multiple aspects of QbD. An understanding of the relevant applied statistics will be offered, which will help participants understand how statistics can be used to help in two foundational requirements of QbD: A) Setting specifications, and B) Analyzing measurement systems.

Important tools for facilitating understanding

This seminar will also offer tools to participants, which will help them to derive value out of their designed experiments. Generating and analyzing both screening and response surface designs for QbD studies, the ways of using this information: best practices on presentation, setting control plans, constructing control charts, and evaluating process capability are among the other constituents of this course. This course uses the point-and-click interface of JMP software for analyses.

Heath will cover the following areas at this seminar:

o  Implement QbD principles from discovery through product discontinuation

o  Apply statistics to set specifications and validate measurement systems (assays)

o  Utilize risk management tools to identify and prioritize potential Critical Process Parameters

o  Identify Critical Process Parameters and develop a functional relationship between those process parameters and your Critical-to-Quality Attributes (CQAs)

o  Establish your design space

o  Develop a control plan as part of a risk management strategy

o  Ensure your process is in (statistical) control and capable.