The influence of QbD on specific factors
How does QbD influence other factors in an outsourced project, such as the type and frequency of communication, the level
and type of testing, and costs?
Successfully outsourcing QbD activities requires quality communication. By its very nature, large amounts of data may be
generated, so expectations around data sharing and presentation need to be clearly defined from the outset. Expectations around
the format and detail of development reports should be shared and defined up-front.
During early-phase development, QbD is more about good application of science and well-documented investigations rather than
systematically trying to understand and control all the CQAs of a given process. This early-phase development learning then
forms the basis of later design decisions for investigations aimed at gaining full process understanding. Therefore, the application
of QbD in early development should not have all that much bearing on the level and type of testing and costs.
We would typically execute more complex experimental designs later in development to gain a full understanding of a process
and fully define its design and control space. This takes more time, and costs more than traditional drug-product development
approaches. However, if this investment is made at the right time, it represents value for money and can offer savings in
the long term by preventing issues in the commercial supply chain.
The greater collaboration and knowledge sharing that is required leads to more efficient and targeted communications (i.e.,
more frequent earlier in the life cycle, less frequent later). With better understanding and control over key product attributes,
cost of manufacture could decrease over the product life cycle compared with more traditional development processes.
QbD certainly drives a higher level of communication and interaction between the pharmaceutical company and the CMO. The
amount of data exchange and transparency required to execute QbD functions strengthens the project management relationship.
Protocol development, execution, and testing is a joint exercise between a customer and CMO. Also, the increased manufacturing
activity in the design space required to challenge the process boundaries increases the quantity of batches produced in development.
This model appropriately shifts costs to the front end of the product-development life cycle, where they can be mitigated
and optimized. Once the process is filed, significant changes are much more costly and time-consuming.
Communication is a key factor in an API development project applying QbD principles. Weekly teleconferences are typical with
written technical updates required at least one day prior to each teleconference. The CMO's project team and the client's
technical staff function as a team in these efforts. During DoE work, data are often communicated immediately to the client
for review and assessment versus further experimentation plans. The amount and type of experimental processing and analytical
testing required often expands beyond the original scope of the initial project. This requires that both the CMO and the client
keep track of the efforts, results, and expenditures versus the scope of the business agreement. A flexible project scope
design is typically warranted where variances within acceptable percentages are allowed without formal approval.
The companies that best understand the QbD concept also tend to have a technology-transfer process with various stage-gate
reviews and communication networks established. A less controlled arrangement up front may start quicker, but they never finish
on time or on budget.