Reporting the DoE part of a design space

By Gitte Nomanni Holm

Quality by design and design space are concepts that have been around for quite some time in the pharmaceutical industry. Slowly the industry has warmed up to these concepts. Since the authorities provided the industry with guidelines, the interest has increased even more. The vision of filing a design space is ambitious and may feel overwhelming when first proposed. However, over the years more and more knowledge has accumulated and the industry seems ready to take the next step. When taking this step a frequently asked question is: “How do we report the DoE part of a design space document internally as well as to the authorities?” In design space projects different departments are commonly involved. Therefore a standard operating procedure (SOP) to avoid errors due to misunderstandings is necessary.

This article will focus on the DoE part of the design space and on the workflow to establish before creating a successful report. A detailed white paper on creating and reporting a design space can be found on www.ngpharma.eu.com.

Establishing a design space is a process starting by defining the critical process parameters (CPPs) and the critical quality attributes (CQAs). Design of experiments (DoE) is used to identify the important CPP's and their impact on the CQAs.

The outcome of the DoE investigations should be judged on two criteria resulting in a case categorisation: (1) are the CQA inside or outside the specification limits and (2) is the model statistically significant or not. Below the different cases are outlined and a work flow of defining a final design space is given.

When starting the project of establishing and filing a design space, it is extremely important that the teams from the different departments 'start on the same page', communicate and use the same terminology. Structure from the beginning to the end is Alpha and Omega for the filing process to run smoothly. Trivial things, such as an inconsistent naming of the input parameters (CPPs) and output parameters (CQAs) and their abbreviations can lead to numerous rewrites, if not addressed at the beginning.

Communication is the key word. Start the project by gathering a representative from each involved department and discuss the topics in this section. Communication is the key and small misunderstandings can take a long time to realise and to correct.

A trivial thing such as naming and abbreviations can build a bottleneck if not organised from the beginning. To avoid this, create a file where abbreviations and names are given in alphabetical order. Make this file accessible to all involved parts in the project. Assign a person from each department to communicate with the other departments so that the used names are unique and not used for another CPPs or CQAs.

Another thing that is of high impotency, when filing a design space, is the traceability. Choose software that allows the name of the experiment to be traceable and visible in all plots.

Creating the report of the design space itself runs rather smoothly if the above issues have been handled properly. The report can be build around a predefined template; such a template has been created by Umetrics and can be accessed by contacting Umetrics. Apart from a general section in the template, revolving type of design, quality of design, as well as a list of the CPPs and CQAs the template also consists of an analytical part build around the four cases above. For each case, specific plots are suggested. Below is a list of plots to use for the four cases. Optional plots are also listed with the rational on when to use them.

Note that Case 2 has many opportunities for different illustrations. This is of course related to the fact that this case does not represent a robust system as the CQAs are outside specification and there exists a significant relationship between changing the CPPs and the CQAs. An example of Case 2 and the reporting can be found in the full white paper at www.ngpharma.eu.com.

Biography

Gitte Nomanni Holm is Application Specialist at MKS Umetrics AB, the leading provider of design of experiment and multivariate data analysis software and consultancy. She has written close to ten technical design space reports that have been used for filing to authorities.