In the previous blog on "Transitioning to QbD," it was noted that QbD workers will need an accessible modeling and simulation environment for QbD to achieve a central role in pharmaceutical development. Discussions with workers indicate that they are currently using a bewildering array of software, which was not designed for QbD. Some software like DOE software is highly restrictive and performs a limited subset of QbD tasks.  Other software like general purpose statistical analysis software is too broad and performs many more tasks than necessary for QbD.  The net result is that today QbD work processes involve a complex combinatorial array of software to get the QbD work done.

Unfortunately cobbling together software from a variety of internal and external sources, illustrated above, has led to an array of problems and shortcomings including the following:

• QbD workers get a lot more features than they need for completing QbD tasks.
• There is huge learning and retention problem for QbD workers.
• QbD workers are faced with complex data integration and management issues.
• There is no audit trail of how the results were obtained.
• Assembling QbD results require inefficient and non-reproducible cut-and-paste processes.
• There is no easy way to extend the functionality of the software as functions are hard wired in.
• And, the situation is costly to set up and maintain.

My experience in developing and implementing electronic lab notebooks in pharmaceutical R&D as replacements for the paper notebook (P. van Eikeren, "Intelligent Electronic Laboratory Notebooks for Accelerated Organic Process R&D," Organic Process Research and Development 2004, 8, 1015-1023) made it clear that pharmaceutical R&D workers expect focused software tools, devoid of extraneous functions, designed to help them get their jobs done.  General purpose tools simply won't do.  In response to this need, Blue Reference has initiated a project, entitled Inference for QbD project, directed at development of a software umbrella appropriate for implementation of QbD practices.  The Inference for QbD project, described on the website at www.InferenceForQbD.com, encompasses a number of novel elements including the following:

• A comprehensive software solution for the implementation of QbD practices in a pharmaceutical environment;
• It is being constructed on the patent-pending Inference platform developed by Blue Reference;
• Users access it through the easy-to-use and familiar user interface of Microsoft Office;
• It is being progressed from technical feasibility to development in a project funded by the National Science Foundation (NSF) Small Business Innovation Research (SBIR) program; and
• It is being development into a commercial product within the context of a consortium of pharmaceutical companies whom are providing guidance on requirements and testing prototypes in production settings.

Pharmaceutical customers tell us that Inference for QbD should address the needs of a broad audience and enable guided decision making-that is, analyze development and manufacturing data within the context of QbD objectives with the intent to identify the best way to move pharmaceutical development forward.  The resulting implementation, illustrated in the figure above, represents a greatly simplified approach to the implementation of QbD practices. Specific benefits include the following:

• Capabilities of the software are tailored to QbD requirements and can be further tailored to company-specific best practices;
• Users only see the functions that they need to get the job done without extraneous distractions;
• Users experience a shallow learning curve as a result of using the familiar Microsoft Office interface;
• Data preparation and management are tightly integrated;
• The software enables concurrent data assembly and preparation, analysis and documentation, thereby providing an audit trail of how the results were obtained;
• The software generates QbD results documents automatically with the press of a single button;
• The software is adaptable and extensible using the Inference platform SDK allowing for future extension and re-direction; and
• The software is inexpensive to set up and maintain because it is based on Microsoft Office, which is already deployed.

Demonstration of these benefits through relevant, illustrative examples will be the subject of future blog entries.