Other contract manufacturers further point to the deepening of the outsourced relationship. "QbD helps inform API selection,
drug formulation, and manufacturing processes upfront, potentially resulting in better, more optimized drug design," says
Jan-Olav Henck, senior director of scientific operations at Aptuit (Greenwich, CT), a contract manufacturer of APIs and finished
drug products and a provider of formulation-development services. "Rather than changing the relationship between sponsor companies
and their outsourcing partner, QbD aligns well with outsourcing relationships based on scientific expertise that generates
high-quality data that can then be strategically applied to the drug-development process."
As an example, Aptuit recently developed a solid-state chemistry production screen. "The production screen applies the practical
application of advanced theoretical developments to increase our understanding of APIs and drug formulations," says Henck.
"We're able to characterize the proclivity to change a compound when introducing mechanical pressures, and we apply that
information to contribute to the development of safe and effective drugs by enabling reproducible and predictable performance
at critical interfaces in the drug-development process."
Ash Stevens (Detroit, MI), a contract manufacturer of APIs, also points to how its approach is aligned with QbD. "After the
basic process is identified, we can perform parametric studies to identify or confirm the critical process parameters," says
Gary A. Baker, vice-president of quality assurance and regulatory affairs for Ash Stevens. "We can use the information obtained
to perform process optimization. We can then perform one final set of experiments to challenge the process to demonstrate
that purity and quality will be maintained at the extremes of the critical parametric ranges. When the process transfers to
manufacturing, we continue to build a lot history to keep the process under control. We can insert 'alert-limits' and 'action-limits,'
tighter than those limits in the regulatory filing, to make us aware of undesirable trends."
Others point to the value of QbD. "QbD encourages use of in-process controls to reduce risk," says Carl I. Oberg, president
of Pharma Tech Industries (PTI, Royston, GA), a contract provider of manufacturing and packaging services for prescription
and over-the-counter drugs. As a contract manufacturer, PTI already uses in-process testing as a control mechanism to ensure
quality products prior to quality-assurance release testing and to reduce the risk of further stage processing of materials
that may be compromised. However, we are seeing more customers willing to entertain the idea of in-process testing and statistical
process control to ensure the lot being produced is of the optimal quality throughout the lot."
Risk mitigation is one benefit of in-process testing and provides a business case for QbD. "Incorporating more in-process
control mechanisms that give real-time feedback should reduce risks," says Oberg. "In-process controls not only ensure a quality
product, but also reduce financial risk associated with high-cost excipients and active pharmaceutical ingredients. We do
see the pharmaceutical industry evolving into this approach and feel that contract manufacturers will need to participate
in order to assess the best approach for process monitoring and correct sample sizes. This approach is not only good for the
quality of the product; it is also good business sense."
Read another perspective on ICH Q10 from FDA's Grace McNally.