From your view as a contract development and management organization (CDMO) or contract manufacturing organization (CMO),
has quality by design (QbD) influenced the expectations between suppliers and pharmaceutical companies?
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Historical relationships were commonly based on providing task-orientated services with a large degree of knowledge and process
understanding still residing within the client organization. Small and mid-cap pharma companies have been quicker to move
away from the functional outsourcing model to leverage the growing expertise in leading CDMOs. As the larger pharma companies
seek to externalize more development activities, there are signs that they are also interested in leveraging the capabilities
of leading CDMOs. The expectations today are that relationships will be far more collaborative in nature with clients demanding
not only technical execution of tasks, but also that the CDMO takes fuller responsibility for technical direction and decision-making
throughout the overall development process. The CDMO accumulates a lot of product-specific knowledge through the execution
of QbD activities and becomes an important partner for the pharmaceutical client. Effective management and communication of
knowledge between client and CDMO will have a heavy influence on the success of the relationship.
From the perspective of a solutions provider, it has been recognized by customers that adherence to the QbD process contributes
to a robust approach throughout all phases of the development process. Successful QbD implementation requires a greater degree
of collaboration and sharing of knowledge and experience to ensure identification of these critical areas and the implementation
of a suitable feedback loop and control strategy to maintain product quality.
Adoption of QbD provides a common language for the development and commercialization of products. Applying the same terminology
(i.e., critical quality attributes [CQAs], critical process parameters, design space, and control strategy) when discussing
strategies helps to prevent any misunderstandings. Having shared goals and understanding will lead to quicker and more effective
decisions, which in turn will speed up the process of developing new products. This could ultimately lead to stronger partnerships
built on trust and mutual understanding.
In general, the QbD initiative has not had a significant impact on current relationships nor the expectations from our customer
base due to the large volume of technology-transfer activity that we conduct. However, with customers that are in the early
stages of manufacturing development, we have seen a stronger emphasis in deploying QbD and process analytical technology (PAT)
methods. The ability to design and execute this work has become an expectation from these customers. This is evident in the
structure of projects with respect to the volume and scope of development activity, as well as the amount of interaction required
to execute the project. Building relationships off of technical capability, execution, and continuous improvement is always
a good approach for a CMO.
Figure 1: From left to right, John McQuaid, technical development manager with Almac; Andy Jordan, product development manager
at Catalent Pharma Solutions; Bruce Herring, manager of operations excellence at DSM Pharmaceuticals; Dwight Lewis, vice-president
of quality operations and regulatory affairs at IRIX Pharmaceuticals; and Tom Beil, vice-president of quality and regulatory
affairs at SAFC.
Lewis ( IRIX):
The QbD initiative has influenced the relationship that IRIX, as a CMO, has with its clients and it has changed the expectations
of some clients relative to the service provided for active pharmaceutical ingredient (API) projects in clinical development.
There is increased emphasis on expanded data analysis during laboratory-scale route scouting and during initial scale-up runs
used to provide API for use in toxicology studies and Phase I clinical support. This expanded data analysis often accompanies
project deliverables such as experimental plans using statistical design of experiments (DoE ) and multivariate designs much
earlier in the development timeline than previously. Active scientific communication and exchange relative to these efforts
require technical involvement from process engineering and manufacturing technical resources much earlier to provide adequate
risk assessment to cover the key process areas that are critical for control. This does not always mean that a 'design space'
is created to support a QbD submission, but the final process-control strategy based on a criticality assessment for the API
is still the goal.
It is not a universally accepted practice with all of our customers, but we work with a technology-transfer process that
moves the transfer toward QbD.