Performance metrics, such as quality, reliability of supply, and timeliness are all important factors in evaluating CDMOs
and CMOs. What additional metrics may be factored into a project that is being developed or manufactured in a QbD paradigm
or how may QbD alter the evaluation process?
A CDMO needs to deliver on these typical contractor metrics; they are the basis of any good service provider–client relationship.
Also, a measure of the effectiveness of communication and the flexibility and problem-solving capabilities of the contract
organization should be factored in. This can often be difficult to quantify as it is not entirely tangible and is often based
on an individual's expectation, but it is critical to the success of projects of this nature and also the effectiveness of
the collaborative relationship.
One metric could be 'right first time' new product introduction. An enhanced product and process understanding backed up
with development data that has been focused on those areas critical to product quality should result in reduced variability
and ultimately lead to a smooth technology transfer as the process is scaled up to the commercial batch size.
QbD is all about understanding the manufacturing process with the premise that this understanding will lead to a more capable
and predictable process. The automotive industry has taught us volumes about understanding and controlling process capability.
The application of statistical process control and capability indices (i.e., Cp, Cpk) are entirely appropriate to pharma processes
as well, especially during in-process measurements. Monitoring variation and then subsequently mitigating or controlling that
variation to design specifications will ensure that the output of that process is predictable. A CMO's knowledge and capability
to execute QbD/PAT initiatives should be an important part of the evaluation process for any customer looking to develop a
product that requires new drug application (NDA) submission.
: Clients seeking to use QbD principles look for a CMO that is able to develop statistical designs and conduct statistical
analyses of large bodies of data in a timely fashion. Many clients want a CMO that is amenable to a "man in the lab" during
execution of designed experiments and a "man in the plant" during actual development and demonstration manufacturing runs.
: It is easy to judge the CDMO or CMO, what is more difficult is to judge yourself. Quite often the product is still in development
during the transfer process. I have seen the conditions of in-process specifications set but not the analytical methodology.
This can lead to misleading results and inaccurate controls.
QbD in today's marketplace
As a CDMO/CMO, have you observed more interest by pharmaceutical companies in QbD as part of a project?
There has been an increase in requests to consider QbD during development projects. For new clients, once we understand the
target product profile and the manufacturing processes that may be used to manufacture the client's product, we can usually
give examples of what an appropriate QbD approach may look like in terms of scope of work. Where we have a strategic relationship
with a client, this process is simpler because there is already an understanding of what is expected.
: QbD is becoming more prevalent in discussions as industry adoption accelerates.
We have observed a strong QbD interest from customers, particularly the technical groups, which are in early-stage development.
With projects where we are getting into the value chain much later, there is not a significant interest in pursuing a QbD
approach although there may be small pockets of QbD or PAT activity.
: IRIX has experienced increased interest is using QbD principles to assess synthetic route selection, determination of critical
process parameters, and critical quality attributes. Prospective risk assessments are now being requested earlier in the clinical
development timeline rather just before registration and process validation of the API.
We work with a wide range of companies on many scales of developed products, and we always prefer to partner with the companies
that have some level of QbD in their program.