For the second case of when a sponsor company and the contract-service provider partner on the development effort, Oates offers
an example of a recent QbD project between Pfizer and a contract-service provider. "The contract-service provider determined
the critical attributes of a functional excipient in the drug-product formulation and their impact on product performance,"
she says. This information was used to determine the specification for the material. The contract-service provider also used
computational fluid dynamics to model the spray-drying process and engineering models to take it to commercial scale. Designs
of experiment for several unit operations were also completed by the contract-service provider. "Most importantly, scientists
from the contract-service provider were vital members of the development team and routinely participated in key meetings,"
she adds. For example, they were also given author access to the documentation system, so they could directly write their
sections of the regulatory submission. "This extent of collaboration, where the contractor is a true partner in the development
process, is unique in our experience," says Oates. "However, it is likely to become more common as the adoption of QbD accelerates,
and outsourcing of development efforts due to technology or cost-drivers increases."
Vendor selection. QbD comes into play not only in the execution of an outsourced project but also in vendor selection. "Material characterization
and identification of significant quality attributes of raw materials (both drug substance and excipients) is an important
aspect of process understanding," says Oates. "In some cases, vendors are willing to work with the sponsor to provide extensive
material-characterization data. This is often the case if the vendor is supplying a new or unique material, but may not be
the case for commodity items. Once the necessary quality attributes are identified, vendors who can routinely supply acceptable
material must be qualified for use. If API manufacturing is outsourced, the sponsor must understand and include known critical
quality attributes into the purchasing and quality agreements. Finally, if a drug product developed using QbD, perhaps including
a novel technology and control strategy, will be outsourced, the vendor must have the technical sophistication and quality
systems to effectively manufacture and test the product."
Supplier performance. QbD also has the potential to change supplier metrics. "Although typical measurements will still be used to evaluate supplier
performance, additional ones will be added," says Oates. "These may include the ability of the supplier to control the product
and process by effectively using the design space; the supplier's commitment to continuous quality verification by evaluating
and communicating to the sponsor the process data that is generated by all lots; and the supplier's willingness to facilitate
regulatory changes to modify or enlarge the design space as allowed by the data."
Contract manufacturers' views
Contract manufacturers also recognize the changing expectations of sponsor companies. "Applying the principles of QbD requires
an holistic approach to drug development and manufacturing, both for contractors and pharmaceutical companies," says Ian Elvins,
executive vice-president of global quality at Lonza (Basel, Switzerland), a contract manufacturer of small-molecules and biologic-based
APIs. "Therefore the principles of QbD can be and should be applied throughout the life of a drug from familiarization and
development through qualification, validation, and production. The QbD approach will be used to streamline development, to
identify potential risks, and to develop ability in products and processes. The risk assessment allows us to tailor the process
development work to the goals needed at a specific point of a product's and process's life cycle. As an API runs through the
phases of its life cycle, the process knowledge grows together with the increasing needs for information."
Lonza is adopting the principles of QbD for both chemical and biologic APIs. It recently made two bolt-on acquisitions to
enhance its technology positions and QbD capabilities for biopharmaceuticals. In November 2009, it acquired Algonomics (Gent,
Belgium), a contract research organization providing immunogenicity screening platforms. In 2007, it acquired AggreSolve,
which provides an in-silico protein analysis platform to solve problems associated with protein aggregation. "The Algonomics
and AggreSolve technologies enable us to identify drug safety or manufacturing challenges early on, which provides the opportunity
to address them and create safer and more cost-effective products," says Elvins.