Ashley Boam, Director, Office of Policy for Pharmaceutical Quality, CDER, U.S. FDA, talked about how the ICH Q12 guideline can be used to overcome barriers to continuous improvement and innovation in her presentation at the 2020 PDA Virtual Annual Meeting on Wednesday, Jul. 22.
In fact, she said the concept of the guidelines resulted from the need to address the multiple global regulatory requirements, uncertain timelines and indeterminate data expectations that prevent companies from improving processes. In her presentation called, “FDA Perspective on ICH Q12,” Boam reviewed the key principles of the Q12 guidelines and the four tools it offers intended to facilitate continual improvement, in particular, established conditions (ECs).
While ECs are the “legally binding information that assures product quality,” confusion has grown over what “each change of each condition established” actually means and whether ECs must be reported if they can be managed solely through a company’s product quality system (PQS). Boam noted that any change requires submission, but all submissions can contain a combination of ECs and supporting information.
Boam suggested that, in submissions, industry can help by giving regulators a better understanding about how their ECs were identified and defined. The extent of ECs varies based on multiple factors, including product and process understanding which, in turn, can draw on various sources, from development studies to commercial experience. That, she said, is why Q12 is careful not to restrict when ECs are put in place.
She went on to explain the differences between “parameter-based” (traditional) and “performance-based” approaches in defining ECs for the manufacturing process. Once they are identified, applicants can propose reporting categories for post-approval changes (PACs) based on potential risk to quality. Using blending as an example, she illustrated what reporting categories might be proposed for different ECs given the types of development approaches.
The key enablers for identifying ECs in an application, she said, should address both the impact of the element on quality and the impact of changing the element on quality and should define a clear approach to criticality and risk assessment. She also illustrated how the key enablers for ICH Q12 relate to elements of ICH Q10 in developing an effective PQS, which can promote regulator confidence in EC proposals.
In closing, Boam said ICH Q12 provides multiple tools that encourage continual improvement and innovation, and ECs provide additional regulatory flexibility in managing PAC CMC changes. “Robust product and process understanding and effective PQS,” she said, “are key enablers of the successful use of these tools.”