Enhanced process and product understanding are the basic tenets of Quality by Design (QbD). Although significant advances
have been made in this respect, appropriate characterization and management of raw materials remains a concern for the regulatory
authorities. In view of the large number of raw materials that typically are used in biotech processes, a QbD-based approach
for raw material management must be based on scientific knowledge and risk analysis. This will ensure that adequate characterization
is performed on those raw materials that are expected to have the most effect on process consistency and product quality.
Part 1 of this article will present an approach for raw material management following the QbD principles. Part 2 will discuss
how to conduct risk assessments, and will give an example of the application of risk assessment tools for raw materials in
The contribution of raw materials to product quality, safety, and process performance is considerable. It is therefore important
in designing processes and selecting raw materials that thought is given to understanding their purpose and suitability for
intended use. Raw materials also are a major source of variability and steps must be taken to minimize any negative impact
arising from materials and their sources. There are essentially two parts to this; prevention, through assessment, inspection,
and control of incoming materials; and intervention, in which processing conditions are modified to account for the variability,
sometimes through continued monitoring of materials and their impact on process performance.
Anurag S. Rathore, PhD
An initial assessment of materials must extend beyond the material specification and its direct effect on the process to include
a host of additional issues such as the supplier's manufacturing processes, quality systems, and sourcing strategy. This is
particularly true of biopharmaceuticals, where processes are highly complex and a wide range of different materials are used
which can affect quality and process performance in both subtle and catastrophic ways, as with the recent experiences of heparin
and melamine contamination. It is necessary to characterize and understand how these interactions can occur, and if they affect
the process or product negatively, but it is unrealistic and impractical to explore every possible permutation of material
variables and process parameters. Modern design approaches recommend taking a science- and risk-based approach to development1 and the following sections will focus on how risk management practices can be applied to prioritize the required studies.
Part 1 of this 20th article in the Elements of Biopharmaceutical Production series presents an approach for raw material management for biotech therapeutic products following the Quality by Design
(QbD) principles. Part 2 will discuss how to conduct risk assessments, handle risk communication to stakeholders, and also
will give an example of the application of risk assessment tools to raw materials for biotech processes.