Greater process understanding is at the core of QbD. In what ways can a CDMO/CMO facilitate that understanding?
Due to the nature of the CDMO business, employees will typically have worked on many more compounds than their counterparts
who have stayed solely within one large pharmaceutical company. The knowledge and experience of working with different materials
and dosage forms can be invaluable to our pharmaceutical clients during design of experiments (i.e., selection of critical
investigation factors and definition of CQAs). There are also differing opinions between regulatory agencies and pharmaceutical
companies as to what the QbD initiative translates to in practical terms. CDMOs can often offer a balanced opinion on how
to implement QbD by having had the experience of working with a wide range of parties in this particular area.
CDMOs within larger integrated contract service providers are well placed to provide pharmaceutical organizations with whatever
support they need to complete their required process understanding, whether that be understanding API manufacturing processes,
characterization of input materials, formulation design and scale-up experiments, design and execution of process-optimization
experiments, or even applying QbD principles to analytical method design and validation. The quality system of the CDMO must
be capable of supporting QbD activities with up-to-date templates for conducting risk assessments and capturing the rationale
behind design of experiments (DoE) activities. Project management of QbD activities is also an important function to offer
as there are a lot of stakeholders from many different disciplines involved. Facilitating knowledge transfer and ensuring
that decisions are made within the individual project constraints are critical.
: A shared knowledge-management system effective across the product life cycle enhances product and process understanding.
A central store of key product information supplemented by all parties involved in development will allow for more efficient
and effective decisions. The manufacturer must provide detailed assessments of key product attributes during process
development and scale-up. This information can then be accessed when the product is in commercial manufacture and an excursion
occurs, which is outside the limits within the batch manufacturing records, but may still be within the design space for the
product. If this information is easily accessible, then a decision on how to proceed can be taken more efficiently and expeditiously.
During the development process, this knowledge can be used when working on similar products, which will simplify and ensure
a more targeted approach and could ultimately reduce project timelines. A knowledge-management system will encourage a culture
of cross-functional collaboration and bidirectional flow of information as teams engaged in development and commercial manufacture
update and share their knowledge.
CMOs execute a wide range of processes across numerous drug formulations while using excipients, raw materials, and APIs
with various characteristics. The cumulative experience and learnings from these diverse activities can be tapped into by
CMOs and used to build the design space. CMOs often perform formulation development, scale-up, and process validation for
small or virtual customers with limited expertise and understanding of regulatory expectations around QbD/PAT. CMO scientists,
engineers, and other technical experts transfer this expertise to customers during these activities. CMOs also have a wide
range of experience with factors such as material transfer, equipment variables, manufacturing environment, and material portfolio.
All these factors are inputs to the design space, and the CMO is in the best position to categorize and quantify these inputs
to help the build the appropriate design model with the customer.
A CMO can facilitate a client's understanding through sharing case studies from previous projects and synthetic development
experiences. An example would be sharing the development of a control strategy with an API process for limiting genotoxic
impurities through developing controls for raw material or intermediate quality attributes rather than using controls in the
API specification. Many clients want to know what a CMO's experience with developing physical property controls consists of,
particularly for solid dosage drug-product development support. A CMO needs to maintain an easy-to-reference knowledge base
of experience in controlling particle size, bulk density, crystallinity, polymorphism, hydration, and solvation of APIs.
One of the problems the pharma and biopharma industries have is the perception that 'no one can do my product as well as I
can.' With so many products developed using a similar platform, the customer should be working on its next product's 'intellectual
property' while allowing the CMO to standardize and optimize the process. All too often when I worked in pharma and now as
a CMO, I have witnessed the transferring company forcing the CMO to change a process to fit the company's unique platform,
only to come back to a more optimized process first offered up by the CMO.