PROGRESS TO DATE
The initial focus of the project has been to define a data structure for the general recipe and physical model based on the
ISA-88 model, and to populate a test database with data from sample processes and equipment lists. The next stage of the project
will involve testing the functions required to transform a general recipe into a master recipe with different scenarios. The
consortium has agreed to follow good automated manufacturing practices (GAMP) during the development process, to allow the
resulting software to be validated where necessary. The benefits of having a validated knowledge-management model include
the potential to extend the data structure and applications into manufacturing and to support scale-up models for regulatory
submissions. The validation approach for the project is to consider each component of the knowledge-management model separately,
starting with a core database, and then to extend the functionality with additional software applications.
An important outcome of the project's requirements-gathering phase was a better understanding of the potential benefits of
the knowledge-management model. By allowing key process information to be systematically captured and retained throughout
development, the model can enable scientists and engineers to learn more effectively from their collective experiences. A
better view of historical performance also enables better predictions of future process performance and costs, and these benefits
will be the focus of the next development stage for the project. The following sections describe some benefits identified
during the planning phase.
IMPROVE METHODS OF WORKING FOR SCIENTISTS AND ENGINEERS
A simple and intuitive approach to managing data involves separating key process information, such as data about process steps
and raw materials, from routine experimental methods and general report information. Storing data and methods separately is
a useful design output in itself, and it supports rapid generation of developmental reports while making it easy to search
for, access, and interpret previous work.
This approach can reduce the time scientists and engineers spend creating documentation; it also simplifies and accelerates
acquisition of data from past studies. For example, a simple data-entry interface can allow process-development scientists
to define process parameters, to reference supporting experiments, and to select buffer recipes and operating methods from
a predefined standards list. This saves them time when creating process documentation. Once a history of experiments and process
definitions is built up over time, the database can also be used as a troubleshooting tool. Engineers can search for information
about an unexpected outcome for a particular unit operation to see if the problem has been previously encountered and if any
workaround solutions have been suggested. Similarly, operations managers can reference information about maximum allowable
hold times for process intermediates during troubleshooting to evaluate whether to proceed with a batch.
PROMOTE STANDARDIZATION AND REDUCE UNCERTAINTY
The increasing popularity of platform processes indicates the value of standardization for bioprocesses. A common data center
that provides access to preferred materials and operating methods can promote the development of robust process designs and
enable process-development scientists to focus on refining those process sections most likely to impact product quality or
process performance. In addition, ensuring that standard representations and terminology are used throughout the process can
reduce confusion during technology transfer and improve communication among groups.
MAXIMIZE EFFECTIVE USE OF BIOPROCESS MODELS
Ultimately, the goal of the knowledge-management model is to enable feedback from manufacturing performance to guide process
development and create a model that supports continuous improvement and better process understanding. Various modeling tools
are commonly used in the industry to gain a better view of the effect of process-development decisions on manufacturability,
and the data model should support more effective use of these modeling tools. By enabling assumptions and relationships defined
in the model to be compared with historical process data, modeling tools can be continually refined and improved. For example,
cost models can assess the impact of process-development decisions on manufacturing costs, and simulation models can assess
facility fit and overall manufacturing performance and resource utilization.
The planning phase for developing the knowledge-management model indicates that a central repository for process data in a
structured format will offer benefits for process development and technology transfer. In addition, the model will support
progress toward improved process understanding. The next development phase will focus on creating applications for defining
and scaling up bioprocesses based on the general recipe concept.
(Companies interested in participating in this development effort are encouraged to contact Andrew Sinclair at BioPharm Services
for further information.)